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Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease
Kim, B.K.,Cho, J.H.,Jeong, P.,Lee, Y.,Lim, J.J.,Park, K.R.,Eom, S.H.,Kim, Y.C. North-Holland Pub ; Elsevier Science Ltd 2015 FEBS letters Vol.589 No.15
Coxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3C<SUP>pro</SUP>) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3C<SUP>pro</SUP> using a FRET-based enzyme assay. Benserazide, whose chemical structure has no electrophilic functional groups, was characterized as a non-competitive inhibitor by enzyme kinetic studies. A molecular docking study with benserazide and its analogs indicated that a novel putative allosteric binding site was involved. Specifically, a 2,3,4-trihydroxybenzyl moiety was determined to be a key pharmacophore for the enzyme's inhibitory activity. We suggest that the putative allosteric binding site may be a novel target for future therapeutic strategies.
한하나 ( H N Han ),엄광문 ( G M Eom ),송은범 ( E B Song ),김철승 ( C S Kim ),허지운 ( J U Heo ) 한국감성과학회 2004 추계학술대회 Vol.2004 No.-
본 연구에서는 교통사고나 뇌졸중 등에 의해 상지의 장애를 가지는 장애인을 대상으로 하여, 인터넷의 브라우저와 같은 소프트웨어를 사용 할 수 있는 컴퓨터 인터페이스로 개발된 Gyro mouse의 성능을 향상시키는 것을 목표로 한다. 그 첫 번째로, 장애인의 경우 휠체어나 침대에 누워서 마우스 조작을 할 수 있도록 시스템의 무선화를 구현하였다. 두 번째로 착탈의 용이성을 위하여 안경 대신 헤드 밴드로 교체하였다. 세 번째로 C5-C6환자들을 위해 클릭 스위치를 구현하였다. 그리고 이 시스랩의 성능 평가를 실제 장애인을 대상으로 실시하였다. 그 결과 정상인에 미치지는 못하지만 시행횟수가 증가할수록 상하/좌우 이동의 오차가 감소하고 분당 클력율이 증가하는 경향을 보였다.
Yoon, J.H.,Kim, H.J.,Park, S.S.,Jeon, Y.W.,Lee, S.E.,Cho, B.S.,Eom, K.S.,Kim, Y.J.,Lee, S.,Min, C.K.,Cho, S.G.,Kim, D.W.,Lee, J.W.,Min, W.S. AMERICAN SOCIETY FOR BLOOD AND MARROW 2017 BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Vol.23 No.4
The role of autologous hematopoietic cell transplantation (auto-HCT) for postremission therapy of acute myeloid leukemia is yet to be elucidated. We retrospectively analyzed 240 patients treated with auto-HCT in first remission. All patients were treated with standard induction chemotherapy, and CD34<SUP>+</SUP>@?stem cells were collected at each cycle of consolidation. Stem cells were infused after total body irradiation (1200 cGy), cytarabine (9 g/m<SUP>2</SUP>), and melphalan (100@?mg/m<SUP>2</SUP>). Estimated 5-year overall survival, disease-free survival (DFS), cumulative incidence of relapse (CIR), and nonrelapse mortality were 58.4%, 55.3%, 38.8%, and 5.9%, respectively. We identified that poor-risk karyotype showed very poor outcome after auto-HCT, and then analyzed 85 patients with good to intermediate-risk molecular cytogenetics with available molecular study results and markers for minimal residual disease (MRD) such as WT1 and core-binding factor (CBF) associated MRD (ie, AML1/ETO and CBFβ/MYH11). Our data identified that old age, pre-HCT markers for MRD, and high post-HCT WT1, high dose of CD34<SUP>+</SUP>@?stem cell (≥4.5 x 10<SUP>6</SUP>/kg) infusion, and c-kit or FLT3-ITD mutations were associated with higher relapse rate and poor DFS. Using pre-HCT parameters, except for post-HCT WT1, multivariate analysis revealed that patients with young age (<40 years old), no adverse mutations, and limited dose of CD34<SUP>+</SUP>@?stem cells might be good candidate for auto-HCT (3-year DFS and CIR were 83.4% and 16.6%, respectively). Young patients with good- to intermediate-risk molecular cytogenetics may benefit from auto-HCT if stem cell dose is limited.
Park, H. M.,Han, S.‐,S.,Lee, E. C.,Lee, S. D.,Yoon, H. M.,Eom, B. W.,Kim, S. H.,Ryu, K. W.,Park, S.‐,J.,Kim, Y. W.,Park, B. John Wiley Sons, Ltd 2017 British journal of surgery Vol.104 No.2
<P><B>Background</B></P><P>Skin antiseptic agents are used to prevent surgical‐site infection (SSI); few trials have reported the superiority of any specific agent in clean‐contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone–iodine.</P><P><B>Methods</B></P><P>Consecutive patients who underwent clean‐contaminated upper gastrointestinal or hepatobiliary–pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone–iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI.</P><P><B>Results</B></P><P>A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone–iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (<I>P</I> = 0·853). The most common causative organism was <I>Enterococcus faecalis</I>. In subgroup analysis, biliary–pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI.</P><P><B>Conclusion</B></P><P>No difference was detected between chlorhexidine gluconate and povidone–iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (<url href='http://www.clinicaltrials.gov'>http://www.clinicaltrials.gov</url>).</P>
Influence of wavelength-shifting films on multianode PMTs with UV-extended windows
Adamczewski-Musch, J.,Becker, K.-H.,Belogurov, S.,Boldyreva, N.,Chernogorov, A.,Deveaux, C.,Dobyrn, V.,Dü,rr, M.,Eom, J.,Eschke, J.,Hö,hne, C.,Kampert, K.-H.,Kleipa, V.,Kochenda, L.,Kolb, B.,K Elsevier 2015 Nuclear Instruments & Methods in Physics Research. Vol.783 No.-
<P><B>Abstract</B></P> <P>Wavelength-shifting (WLS) films were applied on UV-extended front windows of multianode photomultiplier tubes (MAPMTs) in order to increase the sensitivity of the MAPMTs at shorter wavelengths. The WLS material contained p-Terphenyl as photoactive component, which absorbs shorter wavelength photons ( < 300 nm ) and re-emits fluorescence photons around 350nm, i.e., at the maximum of the PMTs׳ sensitivity. The films were applied by means of dip-coating and the film performance was studied with respect to quantum efficiency, film homogeneity, and crosstalk on the MAPMTs. Using WLS-film-covered MAPMTs in a gaseous Ring Imaging Cherenkov detector, the number of detected photoelectrons per ring increased by up to 21% in an in-beam test.</P>
Gu, G.J.,Lim, S.J.,Ahn, S.i.,Lee, S.C.,Chang, Y.T.,Choi, T.H.,Kim, B.S.,Eom, Y.B.,Lee, N.K.,Youn, H.S. North-Holland ; Elsevier Science Ltd 2014 european journal of pharmacology Vol.742 No.-
The pathophysiological processes of inflammation can lead to a host of diseases, such as periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. The dysregulated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activation play important roles in the development of certain inflammatory diseases. Here, we investigated the effects of CDr10b which is originally developed for a microglia staining probe on inflammation, by modulating NF-κB activation and iNOS and COX-2 expression induced by lipopolysaccharide (LPS) in murine macrophages. The CDr10b suppressed NF-κB activation and iNOS and COX-2 expression induced by LPS. All the results suggest that CDr10b is a promising novel agent for the treatment of inflammatory diseases.
Cho, B S,Eom, K S,Kim, Y J,Kim, H J,Lee, S,Min, C K,Cho, S G,Min, W S,Park, C W,Kim, C C,Lee, J W Macmillan Publishers Limited 2010 BONE MARROW TRANSPLANTATION -BASINGSTOKE- Vol.45 No.10
The transplantation of a large number of stem cells can overcome graft rejection but with the increased risk of GVHD. In this study, we analyzed the outcome of 32 adult patients with acquired severe aplastic anemia (SAA) who were at a high risk for graft rejection, including multiple transfusions (median 147 units, range 20–680) and long disease duration (median 67 months, range 3–347), and who had received both BM and CD34<SUP>+</SUP>-purified PBSCs from an HLA-matched sibling donor to reduce graft rejection. T cells in PBSCs were depleted using a magnetic-activated cell sorting method (CliniMACS system). Conditioning regimens consisted largely of CY and antithymocyte globulin (ATG) with fludarabine (FLU) or procarbazine (PCB). With a median follow-up of 89 months, the 8-year probability of survival was 87.5%. Neutrophils and plts promptly recovered, and none of the patients developed graft failure. The cumulative incidences of acute and chronic GVHD were 9.4 and 18.0%, respectively. Sustained engraftment and excellent survival without an apparent increase in the rate of GVHD in high-risk patients using the current approach showed that high-dose SCT with both BM and CD34<SUP>+</SUP>-purified PBSCs may yield better outcomes in heavily transfused and/or allo-immunized patients with SAA.
Cho, B-S,Lee, S,Kim, Y-J,Chung, N-G,Eom, K-S,Kim, H-J,Min, C-K,Cho, S-G,Kim, D-W,Lee, J-W,Min, W-S,Kim, C-C Macmillan Publishers Limited 2009 Leukemia Vol.23 No.10
The aim of this prospective study was to investigate the feasibility of reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) in 37 adults with high-risk acute lymphoblastic leukemia (ALL) in first (n=30) or second (n=7) complete remission (CR). All patients were treated with fludarabine (150 mg/m<SUP>2</SUP>) and melphalan (140 mg/m<SUP>2</SUP>) followed by transplantation from matched sibling (n=27) or unrelated (n=10) donors. The indications for reduced-intensity conditioning allogeneic SCT (RIC-SCT) were as follows: (1) 50 years, 16 (43.2%) and (2) decreased organ function or active infections, 21 (56.8%). Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor (cyclosporine for sibling and tacrolimus for unrelated transplants) and methotrexate. The cumulative incidence of acute (grades II–IV) and chronic GVHD was 43.2 and 65.6%, respectively. After a median follow-up of 36 months for surviving transplants, the 3-year relapse, non-relapse mortality, disease-free survival and overall survival rates were 19.7, 17.7, 62.6 and 64.1%, respectively. Transplants in first CR showed better transplantation outcomes than those in second CR. The potential of antileukemic activity of chronic GVHD was also found. This study suggests that RIC-SCT is a potential therapeutic approach for adults with high-risk ALL in remission who are ineligible for myeloablative transplantation.