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A-Rum Shin,Hosung Sohn,Choul Jae Won,Byungsoo Lee,Woo Sik Kim,Hyun Bae Kang,김화중,신성재,조상래 한국미생물학회 2010 The journal of microbiology Vol.48 No.4
Mycobacterium massiliense is an emerging pathogen and very similar to Mycobacterium abscessus of rapidly growing mycobacteria in the phenotype and genotype. Pathogenic bacteria secrete a diversity of factors into extracellular medium which contribute to the bacterial pathogenicity. In the present study, we performed the comparative proteome analysis of culture filtrate proteins from a clinical isolate of M. massiliense and M. abscessus strains using two-dimensional gel electrophoresis and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). Interestingly, 9 proteins of M. massiliense were distinctly expressed from those of M. abscessus. Bioinformatic analysis of the identified proteins revealed that 3 unique proteins corresponded to serine/arginine rich protein, membrane protein from Streptomyces coelicolor, and one hypothetical protein from Corynebacterium efficiens YS-314, respectively. Culture filtrate proteins from M. massiliense induced the release of pro-inflammatory cytokines from macrophages in a dose-dependent manner but not that from M. abscessus. Taken together, the functional study on the identified proteins uniquely produced from M. massiliense may provide not only the clues for the different pathogensis, but also help develop the diagnostic tools for the differentiation between two mycobacterial species.
Serodiagnostic Potential of Mycobacterium avium MAV2054 and MAV5183 Proteins
Shin, A-Rum,Lee, Kil-Soo,Lee, Kang In,Shim, Tae Sun,Koh, Won-Jung,Jeon, Haet Sal,Son, Yeo-Jin,Shin, Sung-Jae,Kim, Hwa-Jung American Society for Microbiology 2013 CLINICAL AND VACCINE IMMUNOLOGY Vol.20 No.2
<B>ABSTRACT</B><P>TheMycobacterium avium-M. intracellularecomplex (MAC) causes a pulmonary disease (PD) similar to tuberculosis (TB). Diagnosis of MAC-PD is complicated and time-consuming. In this study, the serodiagnostic potential of the newly identified MAV2054 and MAV5183 proteins was evaluated in subjects with MAC-PD, pulmonary TB, or latent TB and in noninfected healthy controls (HC), together with HspX and the 38-kDa antigen, well-known serodiagnosticM. tuberculosisantigens. All four antigens evoked significantly higher IgG responses in MAC-PD and active TB than in latent TB and HC subjects. Among the antigens, MAV2054 elicited the highest antibody responses in pulmonary TB and MAC-PD patients. IgG titers against MAV2054 and MAV5183 were significantly higher in MAC-PD than in pulmonary TB subjects. In addition, the levels of IgG against all antigens in theM. intracellulareand fibrocavitary forms were higher than those in theM. aviumand nodular bronchiectatic forms, respectively. Based on sensitivity and receiver operator characteristic curve analysis, the best candidates for detection of MAC-PD and pulmonary TB were MAV2054 and the 38-kDa antigen, respectively. In total, 76.0% of MAC-PD and 65.0% of active TB patients were reactive to at least two antigens. In contrast, only 2.8% of HC subjects were reactive with two or more antigens. Our findings suggest that an enzyme-linked immunosorbent assay (ELISA) using the four antigens would be valuable for screening for mycobacterial lung disease, including MAC-PD and pulmonary TB, although it does not provide good discrimination of the disease-causing pathogens.</P>
Byun, Eui-Hong,Kim, Woo Sik,Shin, A-Rum,Kim, Jong-Seok,Whang, Jake,Won, Choul-Jae,Choi, Yohan,Kim, Su-Young,Koh, Won Jung,Kim, Hwa-Jung,Shin, Sung Jae Springer 2012 Journal of molecular medicine Vol.90 No.3
<P>Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most deadly infectious diseases, with approximately two million people dying of TB annually. An effective therapeutic method for activating dendritic cells (DCs) and driving Th1 immune responses would improve host defenses and further the development of a TB vaccine. Given the importance of DC maturation in eliciting protective immunity against TB, we investigated whether Rv0315, a newly identified Mtb antigen, can prompt DC maturation. We found that Rv0315 functionally activated DCs by augmenting the expression of the co-stimulatory molecules CD80 and CD86 as well as MHC class I/II molecules. Moreover, it increased DC secretion of the pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha. Unlike LPS, however, Rv0315 induced the secretion of IL-12p70, but not IL-10. In addition, Rv0315-treated DCs accelerated the proliferation of CD4(+) and CD8(+) splenic T cells from Mtb-infected mice, with increased levels of IFN-gamma, in syngeneic and allogeneic mixed lymphocyte reactions, indicating that Rv0315 contributes to Th1 polarization of the immune response. Importantly, both mitogen-activated protein kinases and nuclear factor kappa B signaling mediated the expression of DC surface markers and cytokines. Taken together, our results indicate that Rv0315 is a novel DC maturation-inducing antigen that drives T cell immune responses toward Th1 polarization, suggesting that Rv0315 plays a key role in determining the nature of the immune response to TB.</P>
CysA2: A candidate serodiagnostic marker for <i>Mycobacterium tuberculosis</i> infection
CHOI, Go-Eun,EOM, Sun-Ho,JUNG, Ki-Hwan,SON, Ji-Woong,SHIN, A-Rum,SHIN, Sung-Jae,KIM, Ki-Hye,CHANG, Chulhun L.,KIM, Hwa-Jung Blackwell Publishing Asia 2010 RESPIROLOGY Vol.15 No.4
<P>ABSTRACT</P><P>Background and objective: </P><P>It is important to identify and test serologically active antigens in order to devise a mixture of antigens or peptides that is most useful for serodiagnosis. This study evaluated the serodiagnostic potential of CysA2, which has not previously been described as a serological antigen, together with those of PstS1, HspX, antigen 85 complex and CFP-10 proteins.</P><P>Methods: </P><P>Serum IgG antibody titres against each antigen and a mixture of the antigens were measured by ELISA, in subjects with pulmonary tuberculosis and in healthy control subjects.</P><P>Results: </P><P>CysA2 showed diagnostic value comparable to that of PstS1 and HspX. Mixtures of these three proteins provided the highest diagnostic sensitivity. CysA2 was useful for identifying patients who did not react to HspX or PstS1, and was most valuable in increasing the sensitivity of testing. Furthermore, CysA2 efficiently overcame the limitation associated with use of PstS1, that is, significantly lower sensitivity for subjects who are negative for acid-fast bacilli.</P><P>Conclusions: </P><P>These findings suggest that CysA2 can be used in combination with HspX and/or PstS1 to increase the accuracy of tuberculosis diagnoses.</P>
Characterization of Immune Responses to Mycobacterium tuberculosis Rv2041c Protein
Kim, Su-Young,Shin, A-Rum,Lee, Byung-Soo,Kim, Hwa-Jung,Jeon, Bo-Young,Cho, Sang-Nae,Park, Jeong-Kyu,Shin, Sung-Jae The Korean Society for Microbiology 2009 Journal of Bacteriology and Virology Vol.39 No.3
Tuberculosis, which is caused by Mycobacterium tuberculosis (M. tb), is one of the most important infectious diseases in the world. Although many functional studies have been conducted on M. tb proteins in the post-genomic era, little is known about the function of many proteins expressed specifically during latency. Previously, we reported that Rv2041c from M. tb H37Rv is highly expressed under conditions of low pH and hypoxia, which represent the in vitro mimicry of latent tuberculosis. In the present study, increased expression levels of Rv2041c under hypoxia and low pH in vitro culture was confirmed by RT-PCR. Interestingly, Rv2041c showed significantly increased expression among genes of the same operon and genes belonging to the same functional group. Finally, the immune responses elicited by the recombinant (r) Rv2041c protein were investigated using ex vivo and in vivo models of M. tb infection. A significantly high level of pro-inflammatory cytokines such as TNF-$\alpha$, IL-6, and IL-12p40 was detected in a dose-dependent manner by treatment of murine bone marrow-derived macrophages with rRv2041c protein. In addition, IFN-$\gamma$ and TNF-$\alpha$ secretion increased after stimulation with purified Rv2041c protein to lymphocytes from latent and active TB mice in a modified Cornell model. In conclusion, our findings suggest that Rv2041c is a new T-cell antigen and could be a potential vaccine candidate against M. tb infection by inducing a strong cellular immune response.
Kim, Jae-Ryoung,Cho, Jung Min,Lee, A-Rum,Chae, Eun Ah,Park, Jin-Uk,Byun, Won-Bae,Lee, Sang Kyu,Lee, Jong-Cheol,So, Won-Wook,Yoo, Seunghyup,Moon, Sang-Jin,Shin, Won Suk Elsevier 2011 CURRENT APPLIED PHYSICS Vol.11 No.1
<P><B>Abstract</B></P><P>We prepared the inverted polymer solar cells (PSCs) with a fluorine-doped tin oxide (FTO) as a transparent electrode and with TiO<SUB>2</SUB>, WO<SUB>3</SUB> and WO<SUB><I>x</I></SUB> as selective charge transport layers. An adequately thick TiO<SUB>2</SUB> nanoparticles layer was employed for covering a very rough FTO surface. Using a solution-based WO<SUB><I>x</I></SUB> film instead of a vacuum deposited WO<SUB>3</SUB> layer in inverted polymer solar cells showed comparable device performance. A self-assembled molecular (SAM) layer of PCBA and N719 on top of TiO<SUB>2</SUB> improves the device performance by reducing the series resistance at the interface between the active layer and the TiO<SUB>2</SUB> film. The power conversion efficiency (PCE) was improved by 16%, especially in the case of [6,6]-phenyl-C<SUB>61</SUB>-butyric acid (PCBA).</P> <P><B>Highlights</B></P><P>► Inverted polymer solar cells on FTO electrode with various buffer and SAM layers. ► TiO<SUB>2</SUB>, WO<SUB>3</SUB>, and WO<SUB>x</SUB> films were used as selective charge transport layers. ► WO<SUB>x</SUB> film is good for low cost, easy fabrication and large area solar cells. ► The self-assembled molecular layer of PCBA and N719 on top of TiO<SUB>2</SUB> improves the PCE.</P>
Lee, Kil-Soo,Dubey, Vinod S.,Kolattukudy, Pappachan E.,Song, Chang-Hwa,Shin, A-Rum,Jung, Saet-Byel,Yang, Chul-Su,Kim, Su-Young,Jo, Eun-Kyeong,Park, Jeong-Kyu,Kim, Hwa-Jung Published by Elsevier/North Holland on behalf of t 2007 FEMS microbiology letters Vol.267 No.1
<P>The lipids located in the outer layer of Mycobacterium tuberculosis, which include sulfolipid, phthiocerol dimycocerosate (PDIM), diacyltrehalose, and polyacyltrehalose, may play a role in host-pathogen interactions. These lipids were purified using thin-layer chromatography, and their ability to induce proinflammatory cytokines in human monocytes and in a human acute monocytic leukemia cell line (THP-1) was examined. None of the lipids tested induced significant interleukin (IL)-12p40 or tumor necrosis factor (TNF)-alpha production in monocytic cells. Diacyltrehalose significantly inhibited lipopolysaccharide- and M. tuberculosis-induced IL-12p40, TNF-alpha, and IL-6 productions in human monocytes, whereas other lipids had no effect. However, diacyltrehalose was unable to inhibit peptidoglycan-induced IL-12p40 production. These results suggest that diacyltrehalose is a mycobacterial factor capable of modulating host immune responses.</P>
Kwon, Yu-Mi,Jung, Ki-Hwan,Choi, Go-Eun,Shin, A-Rum,Lee, Byung-Su,Won, Choul-Jae,Kim, Woo-Sik,Shin, Sung-Jae,Park, Jeong-Kyu,Chang, Chul-Hun L.,Kim, Hwa-Jung 대한미생물학회 2009 Journal of Bacteriology and Virology Vol.39 No.4
It is important to identify and to test serologically active antigens, so as to devise a cocktail of the best antigens or peptides. We searched for antigens that have serodiagnostic utility using two-dimensional fractionation of sonic extracts from Mycobacterium tuberculosis and probing with pools of sera from healthy subjects and patients with tuberculosis (TB). Reactive protein spots with patient sera were identified by tandem mass spectrometry. Three proteins, Rv0652, Rv2626c, and Rv3418c, which have not previously been described as serologic targets, were identified. Rv0652 protein among them was expressed in Escherichia coli and serum IgG antibodies against this antigen were measured in 150 patients with pulmonary TB and in 115 healthy subjects. The sensitivity and specificity were 39% and 92%, respectively. These results suggest that a newly identified protein, Rv0652 may be a valuable candidate to be included in a cocktail test kit for TB diagnosis.