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>

Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration

Song, D‐,S.,Park, J‐,C.,Jung, I‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,K.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.2

<P> <I>Song D‐S, Park J‐C, Jung I‐H, Choi S‐H, Cho K‐S, Kim C‐K, Kim C‐S. Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein‐2 on periodontal regeneration. J Periodont Res 2011; 46: 193–203. © 2010 John Wiley & Sons A/S</I> </P><P><B>Background and Objective: </B> Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) is a potent inducer for the regeneration of mineralized tissue, but has a limited effect on the regeneration of cementum and periodontal ligament (PDL). The aim of the present study was to determine the effects of rhBMP‐2 on the <I>in vitro</I> and <I>in vivo</I> biologic activity of well‐characterized human PDL stem cells (hPDLSCs) and to elucidate the underlying mechanism of minimal periodontal regeneration by rhBMP‐2.</P><P><B>Material and Methods: </B> hPDLSCs were isolated and cultured, and then transplanted into an ectopic subcutaneous mouse model using a carrier treated either with or without rhBMP‐2. Comprehensive histologic, histometric and immunohistochemical analyses were performed after an 8‐wk healing period. The effects of rhBMP‐2 on the adipogenic and osteogenic/cementogenic differentiation of hPDLSCs were also evaluated. The effect of rhBMP‐2 on both soluble and insoluble collagen synthesis was analyzed, and the expression of mRNA and protein for collagen types I, II, III and V was assessed.</P><P><B>Results: </B> In the present study, rhBMP‐2 promoted both adipogenic and osteogenic/cementogenic differentiation of hPDLSCs <I>in vitro</I>, and the <I>in vivo</I> potential of hPDLSCs to form mineralized cementum and organized PDL tissue was down‐regulated following treatment with rhBMP‐2. Collagen synthesis, which plays a crucial role in the regeneration of cementum and the periodontal attachment, was significantly reduced, with associated modification of the relevant mRNA and protein expression profiles.</P><P><B>Conclusion: </B> In summary, the findings of the present study suggest that enhanced adipogenic differentiation and inhibition of collagen synthesis by hPDLSCs appear to be partly responsible for the minimal effect of rhBMP‐2 on cementum and PDL tissue regeneration by hPDLSCs.</P>

d-pinitol regulates Th1/Th2 balance via suppressing Th2 immune response in ovalbumin-induced asthma

Lee, J.S.,Lee, C.M.,Jeong, Y.I.,Jung, I.D.,Kim, B.H.,Seong, E.Y.,Kim, J.I.,Choi, I.W.,Chung, H.Y.,Park, Y.M. North-Holland Pub ; Elsevier Science Ltd 2007 FEBS letters Vol.581 No.1

d-pinitol has been demonstrated to exert insulin-like and anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. Recently, it was shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether d-pinitol regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in OVA-induced asthma model mice. We also examined to ascertain whether d-pinitol could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of d-pinitol before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that d-pinitol plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of d-pinitol in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of d-pinitol.

RIHSA와 131I-Hippuran으로 측정한 심박출량의 비교

김정일,고창순,이안기,길광수,박진영,김동섭 대한핵의학회 1970 핵의학 분자영상 Vol.4 No.2

저자들은 정상성인 남자 11예에서 방사성동위원소인 RIHSA와 (131)^I-Hippuran을 사용하여 체외계측법에 의한 심박출량을 측정하여 다음과 같은 결론을 얻었다. 1) RIHSA를 사용한 심박출량의 측정치는 6750±866ml/min, 심계수의 측정치는 3960±476ml/min./㎡이었다. 2) 131I-Hippuran을 사용한 심박출량의 측정치는 5940±764ml/min, 심계수의 측정치는 3490±396ml/min./㎡이었다. 3) (131)^I-Hippuran에 의한 심박출량의 측정치는 RIHSA를 사용한 심박출량의 측정치의 88%로 나타났으며 양자간의 차이는 통계학적의미를 가지고 있었다(P$lt;0.05). 4) (131)^I-Hippuran을 사용하여 심박출량측정이 가능함을 알 수 있었다. Repeated measurement of cardiac output in the same 11 normal individuals were done with (131)^I-Hippuran and RIHSA. Following results were obtained. 1) The cardiac output measured with RIHSA was 6750±866ml/min. 2) The cardiac output measured with (131)^I-Hippuran was 5940±764ml/min. 3) The relative value of cardiac output measured with (131)^I-Hippuran to that measured with RIHSA was 88 percent, and a statistical significance was found present in the difference.

Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element.

Kim, M-J,Kang, J-H,Park, Y G,Ryu, G R,Ko, S H,Jeong, I-K,Koh, K-H,Rhie, D-J,Yoon, S H,Hahn, S J,Kim, M-S,Jo, Y-H Journal of Endocrinology, Ltd. [etc.] 2006 The Journal of endocrinology Vol.188 No.3

<P>Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and beta-cell proliferation. This study aimed to investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic beta-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position -48; 5'-TAACGTCA-3') of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying beta-cell proliferation by EX.</P>

5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced by <i>Bacteroides fragilis</i> enterotoxin via dissociating the complex of heat shock protein 90 and I&kgr;B&agr; and I&kgr;B kinase-&ggr; in intestinal epithelial cell cultu

Kim, J. M.,Lee, D. H.,Kim, J. S.,Lee, J. Y.,Park, H.-G.,Kim, Y.-J.,Oh, Y.-K.,Jung, H. C.,Kim, S. I. Blackwell Publishing Ltd 2009 Clinical and experimental immunology Vol.155 No.3

<P>Summary</P><P>Enterotoxin produced by enterotoxigenic <I>Bacteroides fragilis</I> (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti-inflammatory molecular mechanism of 5,7-dihydroxy-3,4,6-trimethoxyflavone (eupatilin) was characterized in an HT-29 intestinal epithelial cell line stimulated with BFT. Pre-treatment of HT-29 cells with eupatilin decreased the production significantly of both interleukin (IL)-8 and prostaglandin E<SUB>2</SUB> induced by BFT in a dose-dependent manner. BFT-activated nuclear factor-kappaB (NF-&kgr;B) signals in HT-29 cells and pretreatment with eupatilin suppressed NF-&kgr;B activation that resulted in the significant inhibition of IL-8 and cyclo-oxygenase-2 expression. BFT-induced phosphorylation of both I&kgr;B&agr; and I&kgr;B kinase (IKK) signals was prevented in eupatilin-pretreated HT-29 cells. Transfection of siRNA for IKK-&agr; and IKK-&bgr; decreased the production of IL-8 and prostaglandin E<SUB>2</SUB>; however, the transfection of IKK-&bgr; siRNA showed a more significant reduction of BFT-induced I&kgr;B&agr; phosphorylation compared with that of IKK-&agr; siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT-induced activation of IKK and NF-&kgr;B, suggesting that Hsp90 is associated with a pathway of IKK-NF-&kgr;B-IL-8/cyclo-oxygenase-2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK-&ggr; in BFT-stimulated HT-29 cells. These results suggest that eupatilin can suppress the NF-&kgr;B signalling pathway by targeting the Hsp90-IKK-&ggr; complex in intestinal epithelial cells and may attenuate BFT-induced inflammatory responses.</P>

A Comparison of Nilvadipine and Diltiazem in the Treatment of Hypertension

Park, D. G 大韓臨床藥理學會 1996 臨床藥理學會誌 Vol.4 No.2

Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway

Park, Y-H,Kim, S-U,Kwon, T-H,Kim, J-M,Song, I-S,Shin, H-J,Lee, B-K,Bang, D-H,Lee, S-J,Lee, D-S,Chang, K-T,Kim, B-Y,Yu, D-Y Macmillan Publishers Limited 2016 Oncogene Vol.35 No.27

<P>The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently- expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.</P>

Effects of Dietary Fat Types on Growth Performance, Pork Quality, and Gene Expression in Growing-finishing Pigs

Park, J.C.,Kim, S.C.,Lee, S.D.,Jang, H.C.,Kim, N.K.,Lee, S.H.,Jung, H.J.,Kim, I.C.,Seong, H.H.,Choi, Bong-Hwan Asian Australasian Association of Animal Productio 2012 Animal Bioscience Vol.25 No.12

This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace${\times}$Large White${\times}$Duroc) were used at $71{\pm}1$ kg body weight (about 130 d of age) in 24 pens ($320{\times}150$ cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of $14{\pm}3$ d and the finishing diet was given for periods of $28{\pm}3$ d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.

Effects of Expander Processing and Enzyme Supplementation of Wheat-based Diets for Finishing Pigs

Park, J.S.,Kim, I.H.,Hancock, J.D.,Wyatt, C.L.,Behnke, K.C.,Kennedy, G.A. Asian Australasian Association of Animal Productio 2003 Animal Bioscience Vol.16 No.2

Two experiments were conducted to determine the effects of expander processing and enzyme supplementation of wheat-based diets on growth performance and nutrient digestibility in finishing pigs. For Exp. 1, 60 finishing pigs (average initial BW of 49.5 kg) were fed meal, standard pellets and expanded pellets in a 70 d growth assay. From 49.5 to 79.0 kg, 79.0 to 111.8 kg, and overall (49.5 to 111.8 kg), ADG and ADFI were not affected by pelleting or standard vs expander conditioning (p>0.22). However, from 49.5 to 79.0 kg, pigs fed pellets have greater gain/feed than pigs fed mash (p<0.04), and pigs fed expanded pellets tended to have greater (p<0.10) gain/feed than pigs fed standard pellets. Overall (i.e. from 49.5 to 111.8 kg), gain/feed (p<0.02) and apparent fecal digestibilities of DM (p<0.001) and N (p<0.02) were improved by pelleting the diets. Also, expander processing further improved gain/feed (p<0.06) and digestibility of DM (p<0.04) compared to standard steam conditioning. Scores for keratinization (p<0.002) and ulceration (p<0.003) of the stomach were increased by pelleting, but the mean scores for the various treatments ranged only from 0.05 to 1.08 (i.e., low to mild keratosis and ulceration). For Exp. 2, 80 pigs (average initial BW of 54.1 kg) were fed mash and pellets (standard or expander) without and with xylanase. The enzyme was added to supply 4,000 units of xylanase activity/kg of diet. Adding xylanase to the mash diet improved gain/feed from 90.7 to 115.9 kg (p<0.04) of the growth assay and digestibility of DM (p<0.05) on d 39. However, in pelleted diets, adding the enzyme did not improve growth performance or digestibility of nutrients. Pelleting tended to increase scores for ulceration (p<0.06), and enzyme supplementation decreased stomach keratinization scores for pigs fed the standard pellets (p<0.01). However, as in Exp. 1, the mean scores for all treatment groups were quiet low (i.e., ranging from normal to mild). In conclusion, pelleting improved efficiency of growth, but additional benefits from expander conditioning were observed only in Exp. 1. Finally, xylanase tended to improve growth performance and nutrient digestibility, only in pigs fed mash diets but not in pigs fed pellets.