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고위험군의 원발성 전신성 유전분증 1례 보고 및 조혈모세포이식에 대한 문헌고찰
심준,박수정,엄현석,김기영,박은정,강인중,조병식,이안희,한치화 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2
저자 등은 클론성 형질세포질환과 동반된 젊은 연령의 원발성 전신성 유전분증 환자를 진단하였기에 다발성 골수종과의 감별 진단, 치료 , 예후 및 고용량 항암화학요법과 조혈모세포이식에 관하여 문헌고찰과 함께 보고하는 바이다. Primary systemic amyloidosis (AL) is a rapidly fatal disorder related to plasma cell dyscrasia. Conventional dose of melphalan, which prolongs the duration of survival by about 10 months, does not improve the functions of impaired organs in most cases. The high dose chemotherapy followed by autologous hematopoietic stem cell rescue for AL, in spite of its high treatment-related mortality, is a new approach to achieve high response rate and better survival. We experienced a 35-year old man with AL(involving heart, liver, stomach, kidneys, peripheral nerve, and rectum) who did not respond to the standard schedule of melphalan plus prednisone and had rapidly fatal course with organ failure. Hence, we evaluate its availability by reviewing the recent reports of high dose chemotherapy in AL.
Quantitative analysis of anthraquinone compounds from Senna tora seeds at different ripening stages
Joon-Soo Sim,Soo-Ji Choi,Ji-Seon Kim,In-Jin Ha,Chang-Muk Lee,Bum-Soo Hahn 한국당과학회 2016 한국당과학회 학술대회 Vol.2016 No.07
Senna tora (Cassia tora), a member of Leguminosae, is widely distributed in south-east Asian countries. The dried or roasted seed of Senna tora has been used as one of Oriental medicines for centuries for vision-improving, anti-asthenia and diuretic. Furthermore, many reports related to various biological and pharmacological activities of Senna tora have been published such as anti-inflammatory, anti-hepatotoxic, radical scavenging, anti-allergic, anti-mutagenic, antipyretic, hypoglycemic, anti-fungal and anti-bacterial effects. In this study, we have focused on characterizing and quantifying of anthraquinone compounds from Senna tora seeds during different ripening stages. Ultra-high performance liquid chromatography coupled with diode array detector and electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-DAD-ESI-Q-TOF-MS) was used to investigate the compositional changes of anthraquinone compounds that were involved in ripening of Senna tora seeds. Furthermore, non-targeted UHPLC-ESI-Q-TOF-MS data were subjected to principal component analysis and discriminant analysis to find the potential characteristic components from different ripening stages of Senna tora seeds.
Lee, Soo Ok,Cheong, Hyun Sub,Park, Byung Lae,Bae, Joon Seol,Sim, Won Chul,Chun, Ji-Yong,Isbat, Mohammad,Uh, Soo-Taek,Kim, Yong Hooun,Jang, An-Soo,Park, Choon-Sik,Shin, Hyoung Doo Springer-Verlag 2009 Molecules and cells Vol.27 No.2
<P>The myosin light chain kinase (MYLK) gene encodes both smooth muscle and nonmuscle cell isoforms. Recently, polymorphisms in MYLK have been reported to be associated with several diseases. To examine the genetic effects of polymorphisms on the risk of asthma and related phenotypes, we scrutinized MYLK by re-sequencing/genotyping and statistical analysis in Korean population (n = 1,015). Seventeen common polymorphisms located in or near exons, having pairwise r ( 2 ) values less than 0.25, were genotyped. Our statistical analysis did not replicate the associations with the risk of asthma and log-transformed total IgE levels observed among African descendant populations. However, two SNPs in intron 16 (+89872C > G and +92263T >C), which were in tight LD (|D'| = 0.99), revealed significant association with log-transformed blood eosinophil level even after correction multiple testing (P = 0.002/P( corr )= 0.01 and P = 0.002/P( corr ) = 0.01, respectively). The log-transformed blood eosinophil levels were higher in individuals bearing the minor alleles for +89872C > G and +92263T > C, than in those bearing other allele. In additional subgroup analysis, the genetic effects of both SNPs were much more apparent among asthmatic patients and atopic asthma patients. Among atopic asthma patients, the log-transformed blood eosinophil levels were proportionally increased by gene-dose dependent manner of in both +89872C > G and +92263T > C (P = 0.0002 and P = 0.00007, respectively). These findings suggest that MYLK polymorphisms might be among the genetic factors underlying differential increases of blood eosinophil levels among asthmatic patients. Further biological and/or functional studies are needed to confirm our results.</P>
Park, Soo Hwan,Jeong, Myung Ho,Park, In Hyae,Choi, Jin Soo,Rhee, Jung Ae,Kim, In Soo,Kim, Min Cheol,Cho, Jae Yeong,Sim, Doo Sun,Hong, Young Joon,Park, Hyung Wook,Kim, Ju Han,Ahn, Youngkeun,Cho, Jeong Elsevier 2016 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.212 No.-
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Acute myocardial infarction (AMI) is a risk factor for contrast-induced nephropathy (CIN). We investigated whether pretreatment with statin, N-acetylcysteine (NAC) and sodium bicarbonate (NaHCO<SUB>3</SUB>) reduces the risk of CIN.</P> <P><B>Methods</B></P> <P>We conducted a prospective trial and enrolled a total of 334 ST-segment elevation myocardial infarction (STEMI) patients. Patients were divided into four groups: Group I (statin 40mg), Group II (statin 80mg), Group III (statin 80mg plus NAC 1200mg) and Group IV (regimen of group III plus NaHCO<SUB>3</SUB> 154mEq/L). CIN was defined as ≥25% or ≥0.5mg/dL increase in serum creatinine from the baseline within the 72h after PCI.</P> <P><B>Results</B></P> <P>CIN occurred in 72 (21.6%) patients. The incidence of CIN was the lowest in the group III (14.3%), and multivariate analysis showed the lower incidence of CIN in group III compared to Group I [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.13–0.64, p=0.002]. Admission hyperglycemia [(AHG)>198mg/dL] (OR 2.20, 95% Cl 1.20–3.68, p=0.011) and the use of intra-aortic balloon pump (IABP) (OR 4.20, 95% CI 1.38–12.78, p=0.016) were independent predictors for CIN. The CIN (OR 9.00, 95% CI 1.30–62.06, p=0.026) was an independent predictor for in-hospital mortality.</P> <P><B>Conclusions</B></P> <P>Combination of high-dose statin plus NAC was associated with lower incidence of CIN in patients with STEMI who underwent primary PCI compared to statin only.</P>
연구보문 : 식물에서 인체와 유사한 N-glycan 구조를 가진 당단백질 생산에 대한 최근 연구동향
심준수 ( Joon Soo Sim ),신동진 ( Dong Jin Shin ),한범수 ( Bum Soo Hahn ) 한국국제농업개발학회 2011 韓國國際農業開發學會誌 Vol.23 No.3
Several host systems including mammalian cells, yeasts, plants, bacteria, insects and transgenic animals have been employed to produce recombinant therapeutic glycoproteins. Among them, plant system has many advantages such as the low cost, animal pathogens-free, eco-friendly production, and ease of scale up. However, plants are unable to perfectly synthesize human-type N-glycans of therapeutic glycoproteins. It could represent a severe limitation on the use of therapeutic glycoproteins produced from transgenic plants. In this article, we focus on the importance of N-glycosylation, the advantage of molecular farming and its progress strategies, the difference of N-glycan structure between animals and plants, the risk of potential immunogenicity of plant glycoproteins, the strategies to reduce the potential immunogenicity by N-glycosylation engineering including endoplasmic reticulum (ER) targeting of therapeutic glycoproteins, the inhibition of plant-specific glycosyltransferases, and the expression of human specific glycosyltransferases to synthesis galactosylated and sialylated N-glycans in plants.
연구보문 : 코돈최적화를 통한 합성 조직형 플라스미노겐 활성화인자의 형질전환 담배 내 발현
심준수 ( Joon Soo Sim ),차소영 ( So Young Cha ),한정순 ( Jeong Soon Han ),강솔 ( Sol Kang ),헤마바티 ( He Ma Va Thi ),김용환 ( Yong Hwan Kim ),한범수 ( Bum Soo Hahn ) 한국국제농업개발학회 2010 韓國國際農業開發學會誌 Vol.22 No.4
본 연구에서는 현재 전 세계적으로 혈전용해제로서 널리 사용되어지고 있는 t-PA를 담배에서 생산하기 위해 t-PA 유전자를 코돈최적화를 통해 합성하여 담배 rbcS 프로모터하에서 발현을 유도하였다. 합성된 t-PA 유전자는 발현 벡터를 이용하여 담배 형질전환을 실시하였고, 동물세포 유래 t-PA와의 인공 혈 전용해 활성 및 분자량의 동등성 등의 특성을 규명하였다. 1. 담배의 codon usage에 맞게 t-PA 유전자를 합성하였고, 담배 형질전환체 잎에서 피브린 분해 활성이 있는 효소학적으로 안정된 재조합 t-PA의 발현을 확인하였다. 2. 합성 t-PA 유전자의 담배 genomic DNA내의 삽입과 전사는 PCR과 RT-PCR법으로 측정하였고, t-PA 유전자의 PCR 산물(1.6 kb)을 관찰하여 담배 염색체내에 삽입되어 있음을 확인하였다. 또한 t-PA의 전사체 크기에 해당하는 1.6 kb의 PCR 산물을 관찰하여 담배 잎 내에서 정상적인 전사가 이뤄지고 있음을 확인하였다. 3. 담배 형질전환체 잎의 전체 수용성 단백질 중 합성 t-PA 의 평균 발현양은 0.03 μg/TSP mg으로 측정되었고, 가장 높은 발현양은 0.0903 μg/TSP mg로 관찰하였다. 4. 담배 잎 추출물 내에 존재하는 합성 t-PA 단백질의 피브린 분해 활성은 상업적으로 판매되는 재조합의 t-PA 단백질과 동등한 활성을 나타냈고, 담배 형질전환체들의 피브린 용해 활성의 평균값은 0.2589 cm2 lysis zone을 나타냈고, 피브린 용해 활성의 최대치는 0.9 cm2 lysis zone이었다. 5. 형질전환 담배 잎에서 발현된 재조합 합성 t-PA의 분자량을 분석한 결과 동물세포 유래 t-PA와 유사한 크기의 65 kDa으로 확인하였다. 6. T-PA 단백질을 발현하는 담배 형질전환체들은 식물체의 키, 색깔, 모양, 잎의 개수, 성장속도, 종자의 생산량 등과 같은 표현형에 있어 야생종 담배와 별 다른 차이를 보이지 않았으며 후대에도 안정적인 t-PA 활성을 나타내었다. Human tissue-type plasminogen activator(t-PA) which is found in blood and tissues is one of the proteolytic enzyme. T-PA causes fibrin-specific plasminogen activation that can dissolve blood clots in the vasculature. In order to produce recombinant t-PA(st-PA) proteins in transgenic tobacco plants, the t-PA gene was codon-optimized and cloned into a plant binary vector(p221a-rbcS-st-PA) harboring a tobacco rbcS promoter, a tobacco etch virus leader sequence, an N-terminal signal peptide of the alfala glucose-regulated endoplasmic recticular protein and a 35S terminator. The plasmid was transformed into Agrobacterium tumefaciens EHA105 and then the Agrobacterium-mediated transformation of tobacco leaf discs was performed. The insertion of the st-PA gene in genomic DNA of transgenic tobacco plants and the presence of its transcript were verified by PCR and RT-PCR, respectively. We investigated the fibrinolytic activity of recombinant st-PA proteins and quantified their amount to determine the expression level of st-PA proteins in transgenic tobacco leaves. Enzyme-linked immunosorbent assay determined that the highest level of recombinant st-PA expression was 0.09 μg/total soluble protein(mg) in transgenic tobacco plants. The amount of recombinant st-PA proteins in transgenic plants was estimated to range from 0.001 to 0.009% of total soluble proteins. Immuno-blot analysis of transgenic tobacco leaves revealed a single band of approximately 68 kDa recombinant st-PA proteins. These results demonstrated the expression and in vitro activity of recombinant st-PA in transgenic tobacco plants. Thus it provides the information for the additional production of recombinant pharmaceutical proteins using plant system.