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>

Antibiotic susceptibility and resistance of Streptococcus iniae and Streptococcus parauberis isolated from olive flounder (Paralichthys olivaceus)

Park, Y.K.,Nho, S.W.,Shin, G.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Ha, M.A.,Kim, Y.R.,Dalvi, R.S.,Kang, B.J.,Jung, T.S. Elsevier Scientific Pub. Co 2009 Veterinary microbiology Vol.136 No.1

The rates of antibiotic susceptibility and resistance were investigated in Streptococcus iniae and Streptococcus parauberis isolates obtained from diseased olive flounders (Paralichthys olivaceus) collected from fish farms in Jeju Island, Korea. Isolates of S. iniae (n=65) were susceptible to cefotaxime, erythromycin, ofloxacin, penicillin, tetracycline and vancomycin, as demonstrated by the minimum inhibitory concentration (MIC) test. Isolates of S. parauberis (n=86) were highly resistant to erythromycin (58% of the 86 isolates tested) and tetracycline (63% of the 86 isolates tested). Fifty-four isolates of tetracycline-resistant S. parauberis contained the tet(M/O/S) genes, of which 39 and 12 isolates contained the tet(M) and tet(S) genes, respectively, whereas 3 isolates contained both the tet(M) and tet(S) genes. Among the erythromycin-resistant isolates of S. parauberis (n=50) only 14 contained the erm(B) gene. These results suggest that the tet(S) and erm(B) genes of S. parauberis are involved in the acquisition of high-level resistance to erythromycin and tetracycline. Our findings reveal a high rate of antibiotic resistance among strains of S. parauberis and emphasize the need to develop an appropriate vaccine to reduce the use of antibiotics.

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>

S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

S nutrition alleviates salt stress by maintaining the assemblage of photosynthetic organelles in Kentucky bluegrass (Poa pratensis L.)

Park, S. H.,Lee, B. R.,Lee, J. H.,Kim, T. H. Springer Science + Business Media 2016 Plant growth regulation Vol.79 No.3

<P>To assess the roles of sulfur (S) nutrition in salt stress tolerance in Kentucky bluegrass (Poa pratensis L.). The plants grown in S-supplied or S-deprived condition for 4 weeks were exposed to salt stress with 100 mM NaCl or non-salt stress, respectively, for 21 days. Osmotic potential was significantly decreased by salt stress from day 14. Photosynthetic pigments such as chlorophyll and carotenoid were decreased by salt stress which was more severe in the absence of S, but their content was largely recovered in the presence of S-nutrition. The proteomic analysis of multi-protein complexes in the thylakoid by BN-PAGE showed that the expression of PSI, PSII and RuBisCo level was repressed under salt stress in the absence of S, whereas their expression was largely recovered by S supply. Enzymatic activity confirmed the responses of RuBisCo, estimated by the BN-PAGE, showing a decreased activity in S-deprived and/or salt stressed levels. The decreased RuBisCo activity was significantly related to S content as affected by S nutrition and/or salt stress. Significant relationship between S content and Na, K, Fe content was also observed. These results indicate that S-nutrition modulates the negative responses to salt stress tolerance in photosynthetic organelles of P. pratensis.</P>

하지 정렬 평가를 위한 체표면 토포그래피를 이용한 측정법

임지영(J. Y. Yim),임현승(H. S. Yim),박대성(D. S. Park),이재헌(J. H. Lee),이나경(N. K. Lee) 한국재활복지공학회 2016 재활복지공학회논문지 Vol.10 No.1

이 연구의 목적은 래스터입체사진술이 적용된 ABW-mapper를 사용하여 얻은 관상면 상에서의 하지정렬 측정에 대하여 측정자 내, 측정자 간, 측정-재측정 간 각각의 신뢰도와 타당도를 조사하고 평가하는 것이다. 열여덟 명의 대상자가 이 연구에 참여하였다. 일주일간격으로 두 번의 세션에 걸쳐서 두 사람의 측정자가 각각 ABW-mapper를 사용하여 기립자세에서의 S각(입체사진 각-래스터입체사진 촬영을 통해 측정한 관상면상의 하지 정렬 측정 각)을 측정하였고, 첫 번째 세션에서는 짧은 시간 간격으로 한 측정자가 같은 대상자에 대하여 두 번씩 측정하였다. Q각은 디지털카메라로 기립자세를 촬영한 사진에서 고니어미터로 측정하였다. HKA각은 컴퓨터 기반 디지털 방사선 영상사진 위에서 측정 소프트웨어를 사용하여 측정하였다. 급내상관계수(ICC)를 통해 신뢰도를 분석하였고, 피어슨 상관계수를 사용하여 타당도를 검사하였다. 그 결과, S각 측정은 매우 높은 측정자 내(ICC=0.956~0.974), 측정자 간 (ICC=0.962) 검사-재검사 간 (ICC=0.945) 신뢰도를 나타냈으며, S각과 Q각, S각과 HKA각 사이에는 강한 음의 상관관계(각각 r=0.739, -0.702)를 나타냈다. 따라서, ABW-mapper에 의한 래스터입체사진법을 통한 S각 측정은 관상면에서의 하지정렬의 측정에 대하여 Q각이나 HKA각 측정에 관련하여 예비적 또는 보완적 도구로 사용될 수 있을 것이라 생각된다. The purpose of this study was to assess the intra-rater, inter-rater and test-retest reliability and validity of frontal plane lower extremity alignment estimated from a rasterstereographic method using ABW-Mapper. Eighteen subjects participated in this study. The S angle (stereographic angle-frontal plane lower extremity alignment estimated from a rasterstereographic method) in standing was measured throughout the two sessions with one week interval by two different readers. In the first session, a reader measured S angle twice per subject with a short break in-between. The Q-angle (quadriceps angle) was measured using a standard goniometer from a photography taken through digital camera with the participant standing in the same position as in the S angle measurement. The HKA(hip-knee-ankle) angle was measured from a computer based digital radiograph with the computerized measurement software. Reliability was tested using intraclass correlation coefficients(ICC). Validity was tested using a Pearson’s correlation coefficient. Excellent intra-rater(ICC=0.956~0.974), inter-rater(ICC=0.962), test-retest reliability (ICC=0.945) were demonstrated. There were strong negative correlations between S angle and Q-angle (r=-0.739), and between S angle and HKA angle (r=-0.702). Therefore, the S angle measured using a rasterstereographic mapper may be used to as a preliminary or supplementary tool to evaluate and study LE alignment in the frontal plane in relation to HKA angle or Q-angle.

Sphingosine-1-phosphate-induced Flk-1 transactivation stimulates mouse embryonic stem cell proliferation through S1P₁/S1P₃-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.

CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients

Bae, J.S.,Park, S.H.,Jamiyandorj, U.,Kim, K.M.,Noh, S.J.,Kim, J.R.,Park, H.J.,Kwon, K.S.,Jung, S.H.,Park, H.S.,Park, B.H.,Lee, H.,Moon, W.S.,Sylvester, K.G.,Jang, K.Y. American Association of Pathologists and Bacteriol 2016 The American journal of pathology Vol.186 No.12

<P>Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 alpha 1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, beta-catenin, cyclin D1, and NF-kappa B. Especially, SIRT6 expression was associated with the nuclear localization of B-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.</P>

Complete chloroplast genome sequences of Solanum commersonii and its application to chloroplast genotype in somatic hybrids with Solanum tuberosum

Cho, K. S.,Cheon, K. S.,Hong, S. Y.,Cho, J. H.,Im, J. S.,Mekapogu, M.,Yu, Y. S.,Park, T. H. Springer International 2016 Plant cell reports Vol. No.

<P>Chloroplast genome of Solanum commersonii and S olanum tuberosum were completely sequenced, and Indel markers were successfully applied to distinguish chlorotypes demonstrating the chloroplast genome was randomly distributed during protoplast fusion. Somatic hybridization has been widely employed for the introgression of resistance to several diseases from wild Solanum species to overcome sexual barriers in potato breeding. Solanum commersonii is a major resource used as a parent line in somatic hybridization to improve bacterial wilt resistance in interspecies transfer to cultivated potato (S. tuberosum). Here, we sequenced the complete chloroplast genomes of Lz3.2 (S. commersonii) and S. tuberosum (PT56), which were used to develop fusion products, then compared them with those of five members of the Solanaceae family, S. tuberosum, Capsicum annum, S. lycopersicum, S. bulbocastanum and S. nigrum and Coffea arabica as an out-group. We then developed Indel markers for application in chloroplast genotyping. The complete chloroplast genome of Lz3.2 is composed of 155,525 bp, which is larger than the PT56 genome with 155,296 bp. Gene content, order and orientation of the S. commersonii chloroplast genome were highly conserved with those of other Solanaceae species, and the phylogenetic tree revealed that S. commersonii is located within the same node of S. tuberosum. However, sequence alignment revealed nine Indels between S. commersonii and S. tuberosum in their chloroplast genomes, allowing two Indel markers to be developed. The markers could distinguish the two species and were successfully applied to chloroplast genotyping (chlorotype) in somatic hybrids and their progenies. The results obtained in this study confirmed the random distribution of the chloroplast genome during protoplast fusion and its maternal inheritance and can be applied to select proper plastid genotypes in potato breeding program.</P>

Application of genetically engineered Salmonella typhimurium for interferon-gamma-induced therapy against melanoma

Yoon, W.,Park, Y.C.,Kim, J.,Chae, Y.S.,Byeon, J.H.,Min, S.H.,Park, S.,Yoo, Y.,Park, Y.K.,Kim, B.M. Pergamon Press 2017 European journal of cancer Vol.70 No.-

Salmonella have been experimentally used as anti-cancer agents, because they show selective growth in tumours. In this study, we genetically modified attenuated Salmonella typhimurium to express and secrete interferon-gamma (IFN-γ) as a tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-γ was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant IFN-γ (S. typhimurium (IFN-γ)) invaded the melanoma cells and induced cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-γ) also efficiently inhibited tumour growth and prolonged the survival of C57BL/6 mice bearing B16F10 melanoma compared with administration of phosphate-buffered saline (PBS), unmodified S. typhimurium or S. typhimurium expressing empty vector (S. typhimurium [Vec]) in a natural killer (NK) cell-dependent manner. Moreover, genetically modified Salmonella, including S. typhimurium (IFN-γ), showed little toxicity to normal tissues with no observable adverse effects. However, S. typhimurium (IFN-γ)-mediated tumour suppression was attributed to direct killing of tumour cells rather than to stable anti-tumour immunity. Collectively, these results suggest that tumour-targeted therapy using S. typhimurium (IFN-γ) has potential for melanoma treatment.