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정병천,배호상,곽동훈,김영태,배용학,황종현,임현주,류재근,조용근,채성철,전재은,박의현 慶北大學校 醫科大學 1997 慶北醫大誌 Vol.38 No.2
목적 : 급성하벽심근경색증 환자에서 심전도상 흔히 동반되는 전흉부유도 ST절 하강의 의의를 알아보았다. 방법 : 심근경색후 24시간에서 48시간에 얻은 심전도를 기준으로 52명의 급성하벽심근경색증 환자를 전흉부유도에서 ST절의 하강이 있는 군과 없는 군으로 나누었으며 심도자, 관상동맥조영술, 심초음파도 및 방사성 핵종을 이용한 좌심구혈율 측정 등을 시행하였다. 결과 : 1) 좌심실확장기말압은 전흉부유도에서 ST절의 하강이 있는 경우에서 16.9±5.33mmHg로 없는 경우의 11.0±4.02mmHg보다 유의하게 높았다(p<0.05). 그러나 운동량 및 좌심구혈을은 흥부 유도상 ST절의 하강이 있는 경우 7.6±3.0 METs 및 53.9±9.1%로 없는 경우의 9.1±2.7 METs 및 54.6±9.5%보다 낮았으나 통계적 유의성은 없었다(p=0.180, p=0.823). 2) 관상동맥조영술상 전흉부 ST절의 하강이 동반된 군에서는 유의한 좌전하행지나 좌회선지의 협착이 있는 경우가 60.9% 및 57.9%로 ST절의 하강이 없는 군에서의 34.5% 및 7.7%와 비교해 좌관상동맥에 협착이 동반된 경우가 많았다(p=0.050, p=0.001). 3) 관상동맥조영술상 세 혈관질환의 빈도는 흉부유도상 ST절의 하강을 보인 23예에서 10예로 ST절 하강이 없었던 29예중 2예에 비하여 유의하게 많았고(P=0.007), 단 혈관질환의 빈도는 ST절의 하강을 보인 군에서 23예중 5예로 ST절 하강이 없었던 29예중 17예에 비하여 유의하게 적었다(P=0.002). 두 혈관질환의 경우에는 각각 8예와 10예로 양군간에 유의한 차이가 없었다. 4) 흉부유도상 ST절 하강의 빈도는 단 혈관질환 22예 중 5예에서, 두 혈관질환 18예중 8예, 세 혈관질환 12예 중 10예에서 관찰되어 협착이 있는 관상동맥의 수가 많을수록 ST절의 하강이 나타나는 빈도가 많음을 보였다(p=0.00308). 그러나 흉부유도상 나타난 ST절의 하강을 모두 합하여 구한 ST절 하강의 합은 협착이 있는 관상동맥의 수와 통계적인 유의성이 없었다. 5) 심초음파도상 좌심실 하벽의 벽운동은 ST절 하강을 보인 군에서는 akinesia가 83.3%, hypokinesia가 11.1%, 정상 벽운동이 5.6%로, ST절 하강이 없었던 군에서의 dyskinesia가 3.6%, akinesia가 39.3%, hypokinesia가 25.0%, 정상 벽운동이 32.1%와 비교하여 ST절의 하강이 있는 군에서 유의하게 벽운동의 장애가 빈번함을 보였다(p=0.03891). 그러나 좌심실전벽, 측벽 및 중격부위에서는 유의한 벽운동의 차이가 없었다. 결론 : 급성하벽심근경색증 환자의 전흉부유도에서 ST절의 하강이 동반되는 경우 다혈관 질환의 가능성이 높으며 좌심실확장기말압이 상승되었고 운동능력은 감소되어 있었다. 또한 심초음파도상 좌심실하벽의 벽운동장애도 심하였다. 따라서 전흉부 ST절의 하강을 동반한 급성하벽심근경색증 환자는 전흉부유도에 ST절 하강이 없는 경우보다 예후가 불량할 것으로 생각되며, 보다 적극적인 치료가 필요할 것으로 생각된다. The purpose of this study was to determine the significance of precordial ST segment depression appearing during acute inferior myocardial infarction and to assess the correlation of that with angiographic finding. 52 patients were allocated into two groups based on the existence of precordial ST segment depression : 23 patients with ST segment depression and 29 patients without ST segment depression. The extent of coronary artery disease as well as the prevalence of significant stenosis (≥70%) in left anterior descending artery were more frequent in patients showing precordial ST segment depression than in patients not showing them (p=0.050) and the result were similar in cases of left circumplex artery (p=0.001). On echocrdiographic examination of left ventricular (LV) wall motion, it showed more severely decreased inferior LV wall motion in patients showing precordial ST segment depression than in patients not showing them (p=0.03891) even though the other segment of LV wall motion didn't show the statistical difference between both groups. The other cardiac parameters such as LVEDP, exercise amount (METs) and ejection fraction were tend to showing bad profile in patients with precordial ST segment depression. From the above results, we could deduce that patients with precordial ST segment depression have relatively large infarction or concomitant left coronary artery disease, so they need more caution and intensive theraphy.
Chemical inhibitors destabilize HuR binding to the AU-rich element of TNF-α mRNA
Min-Ju Chae,Hye Youn Sung,Eun-Hye Kim,Mira Lee,Hojoong Kwak,Chong Hak Chae,Sunwoo Kim,Woong-Yang Park 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.11
Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-α mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-α mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC50) below 10 μM. The IC50 of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 μM, respectively, for binding of HuR protein to TNF-α mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-α mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-α mRNA and decreased levels of secreted TNF-α. From these results, we could find inhibitors for the TNF-α mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs. Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-α mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-α mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC50) below 10 μM. The IC50 of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 μM, respectively, for binding of HuR protein to TNF-α mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-α mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-α mRNA and decreased levels of secreted TNF-α. From these results, we could find inhibitors for the TNF-α mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs.
Helix foldamers of γ-peptides based on 2-aminocyclohexylacetic acid: a computational study
Lee, Joo Yun,Chae, Chong Hak,Kang, Young Kee The Royal Society of Chemistry 2014 NEW JOURNAL OF CHEMISTRY Vol.38 No.3
<P>The conformational preferences of helix foldamers have been studied for oligo-γ-peptides of 2-aminocyclohexylacetic acid (γAc<SUB>6</SUB>a) with a cyclohexyl constraint on the C<SUP>β</SUP>–C<SUP>γ</SUP> bond using density functional methods. For the di-γAc<SUB>6</SUB>a peptide with the homochiral (1<I>S</I>,2<I>S</I>) configurations, the right-handed (<I>P</I>) 9-helical structure is found to be the most preferred in the gas phase, whereas the (<I>P</I>) 14-helical structure is favored by ∼0.2 kcal mol<SUP>−1</SUP> over the former in water. As the peptide sequence becomes longer, the (<I>P</I>)-2.5<SUB>14</SUB>-helices are the most preferred for tetra- to octa-γAc<SUB>6</SUB>a peptides both in the gas phase and in water, which is due to the favored conformational energies. The calculated mean backbone torsion angles and helical parameters of the 14-helix foldamers of oligo-γAc<SUB>6</SUB>a peptides are consistent with those of the X-ray structures of C<SUP>α</SUP>-ethyl-γAc<SUB>6</SUB>a peptides. Although the 14-helix foldamers of γAc<SUB>6</SUB>a and 2-(aminomethyl)cyclohexanecarboxylic acid (γAmc<SUB>6</SUB>) oligopeptides have similar mean backbone torsion angles and helical parameters, there are some differences in structure and/or helix handedness for other helix foldamers, which can be ascribed to the different substitutions of the cyclohexyl constraint on C<SUP>β</SUP>–C<SUP>γ</SUP> or C<SUP>α</SUP>–C<SUP>β</SUP> bonds. Therefore, the conformational preferences of the oligo-γAc<SUB>6</SUB>a peptides obtained here are expected to provide useful information for structure-based designs of biologically active γ-peptides with specific functions.</P> <P>Graphic Abstract</P><P>The oligo-γ-peptides based on 2-aminocyclohexylacetic acid (γAc<SUB>6</SUB>a) with a cyclohexyl constraint on the C<SUP>β</SUP>–C<SUP>γ</SUP> bond and the homochiral (1<I>S</I>,2<I>S</I>) configurations adopt preferentially the right-handed 14-helix foldamers in the gas phase and in water. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3nj01217d'> </P>
The Predictive QSAR Model for hERG Inhibitors Using Bayesian and Random Forest Classification Method
Kim, Jun-Hyoung,Chae, Chong-Hak,Kang, Shin-Myung,Lee, Joo-Yon,Lee, Gil-Nam,Hwang, Soon-Hee,Kang, Nam-Sook Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.4
In this study, we have developed a ligand-based in-silico prediction model to classify chemical structures into hERG blockers using Bayesian and random forest modeling methods. These models were built based on patch clamp experimental results. The findings presented in this work indicate that Laplacian-modified naive Bayesian classification with diverse selection is useful for predicting hERG inhibitors when a large data set is not obtained.