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Durable Response to Pazopanib in a Patient with Metastatic Alveolar Soft Part Sarcoma
Jimin Han,Im Il Na,Min Woo Jung,Su Heui Lee,Jae Woon An,Jae Soo Koh Ewha Womans University School of Medicine 2016 EMJ (Ewha medical journal) Vol.39 No.3
Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma, and frequently, metastases are found at diagnosis. In patients with metastatic or unresected ASPS, systemic treatment is extremely limited, because conventional chemotherapeutic agents have not been effective in most cases. A novel agent inhibiting angiogenesis, pazopanib, has been proven to be effective for metastatic soft tissue sarcoma in a second-line setting. However, the efficacy of pazopanib in ASPS has not yet been reported. A 22-yearold man presented with right calf ASPS and multiple lung metastases. Pazopanib as a second-line treatment showed significant tumor response. To the best of our knowledge, this is the first report of the effectiveness of pazopanib in ASPS.
Yunn Na-Oh,Lee Jimin,Lee Hye Sun,Oh Eun Ju,Park Mangeun,Park Seongeun,진서연,Shin Euisu,Lee Jo woon yi,Kim Youndong,배순식,Ryu Sung Ho 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Aptamers are widely used as binders that interact with targets with high affinity or as inhibitors of the function of target molecules. However, they have also been used to modulate target protein function, which they achieve by activating the target or stabilizing its conformation. Here, we report a unique aptamer modulator of the insulin receptor (IR), IR-A62. Alone, IR-A62 acts as a biased agonist that preferentially induces Y1150 monophosphorylation of IR. However, when administered alongside insulin, IR-A62 shows variable binding cooperativity depending on the ligand concentration. At low concentrations, IR-A62 acts as a positive allosteric modulator (PAM) agonist that enhances insulin binding, but at high concentrations, it acts as a negative allosteric modulator (NAM) agonist that competes with insulin for IR. Moreover, the concentration of insulin affects the binding of IR-A62 to IR. Finally, the subcutaneous administration of IR-A62 to diabetic mice reduces blood glucose levels with a longer-lasting effect than insulin administration. These findings imply that aptamers can elicit various responses from receptors beyond those of a simple agonist or inhibitor. We expect further studies of IR-A62 to help reveal the mechanism of IR activation and greatly expand the range of therapeutic applications of aptamers.
한국인에서 개정된 눈 사르코이도시스 진단 기준의 임상적 효용성에 대한 분석
박지민(Jimin Park),김유나(You Na Kim),김윤전(Yoon Jeon Kim),김중곤(June Gone Kim),윤영희(Young Hee Yoon),이주용(Joo Yong Lee) 대한안과학회 2021 대한안과학회지 Vol.62 No.9
목적: 2017년 6차 International Workshop for Ocular Sarcoidosis (IWOS)에서 개정 발표된 눈 사르코이도시스 진단 기준을 2009년 발표된 1차 IWOS 진단 기준과 비교 분석하고, 이를 한국인 눈 사르코이도시스 진단에 활용했을 때의 임상적 효용성을 알아보고자 한다. 대상과 방법: 2007년부터 2018년까지 서울아산병원 안과에서 포도막염으로 진단받은 환자들 중 호흡기내과 및 안과 정밀검진을 시행 후 눈 사르코이도시스로 진단된 환자들의 의무기록을 후향적으로 분석하였다. 내과에서 시행한 혈액검사, 영상학적 검사 및 조직검사 결과와 안과 검진 시 시행한 세극등현미경검사, 안저검사, 형광안저 혈관조영술 결과를 종합하여 2009년 및 2017년 IWOS 진단 기준에 따라 눈 사르코이도시스를 진단하였다. 결과: 눈 사르코이도시스로 진단된 총 34명의 의무기록을 분석하고 두 진단 기준을 활용하여 분류하였다. 조직검사를 시행한 32명의 환자 중 31명이 조직검사상 사르코이도시스로 진단되었다(양성률 96.87%). 31명이 definite ocular sarcoidosis (OS), 2명이 presumed OS로 이전 진단 기준과 개정된 진단 기준에서 동일하게 분류되었고, 1명의 환자만 기존 진단 기준에서는 possible OS, 개정된 진단 기준에서는 presumed OS로 분류되었다. 결론: 조직검사 양성률이 높고, 영상학적 검사의 질이 높은 우리나라의 임상상황에서는 이전 진단 기준과 비교하여 개정된 진단 기준을 활용하였을 때 진단 결과에 큰 차이는 없을 것으로 사료된다. Purpose: To compare differences between the original criteria for diagnosis of ocular sarcoidosis (OS) (first International Workshop for OS [IWOS] 2009) and the revised criteria (sixth IWOS 2017), and their clinical usefulness when assessing OS in Korean patients. Methods: We analyzed patients with suspected OS who visited our tertiary referral ophthalmological and pulmonary clinic from 2007 to 2018. We diagnosed patients using both sets of criteria. Blood test and biopsy data (collected by physicians) and slit-lamp, fundus, and fluorescein angiography data (collected by ophthalmologists) were reviewed. Results: Thirty-four patients were diagnosed using both criteria. Of 32 patients who underwent biopsies, 31 had OS (96.87%). Using either set of criteria, 31 patients were diagnosed with definite OS and two with presumed OS. One patient diagnosed with possible OS using the previous criteria was diagnosed with presumed OS using the revised criteria. The new criteria add the lysozyme level, the CD4/CD8 ratio, and positron emission tomography imaging data to the old criteria and add the descriptors “presumed OS” and “probable OS”. There is no need to use the revised criteria in Korea; the biopsy and imaging data are adequately diagnostic. Conclusions: IWOS revised the OS diagnostic criteria by adding new parameters. However, this was unnecessary for Korea, where the biopsy and imaging data are adequately diagnostic.
Park, Jimin,Yang, Ki Dong,Kim, Na-Young,Jung, Kang-Won,Le, Viet-Duc,Lim, Hee-Jin,An, Junghyun,Jin, Kyoungsuk,Kim, Yong-Hyun,Nam, Ki Tae,Moon, DaeWon American Chemical Society 2018 ACS central science Vol.4 No.9
<▼1><P/><P>One of the remaining challenges in material chemistry is to unveil the quantitative compositional/structural information and thermodynamic nature of inorganic materials especially in the initial nucleation and growth step. In this report, we adopted newly developed time-of-flight medium-energy-ion-scattering (TOF-MEIS) spectroscopy to address this challenge and explored heterogeneously grown nanometer-sized calcium phosphate as a model system. With TOF-MEIS, we discovered the existence of calcium-rich nanoclusters (Ca/P ∼ 3) in the presence of the non-collagenous-protein-mimicking passivating ligands. Over the reaction, these clusters progressively changed their compositional ratio toward that of a bulk phase (Ca/P ∼ 1.67) with a concurrent increase in their size to ∼2 nm. First-principles studies suggested that the calcium-rich nanoclusters can be stabilized through specific interactions between the ligands and clusters, emphasizing the important role of template on guiding the chemical and thermodynamic nature of inorganic materials at the nanoscale.</P></▼1><▼2><P>A new spectroscopy, TOF-MEIS, was utilized to understand templated nucleation of calcium phosphate with sub-nm resolution. The existence of calcium-rich nanoclusters and their growth were discovered.</P></▼2>
Choi, Hyun-Jung,Kim, Na-Eun,Kim, Jayoung,An, Sunho,Yang, Seung-Hee,Ha, Jimin,Cho, Sunghee,Kwon, Il,Kim, Young Dae,Nam, Hyo Suk,Heo, Ji Hoe Pergamon Press 2018 Thrombosis research Vol.167 No.-
<P><B>Abstract</B></P> <P>Dabigatran etexilate (DE), a new oral anti-coagulant, is a direct thrombin inhibitor. Clinical trials showed the favorable benefit-to-risk profile of DE compared to warfarin for the prevention of ischemic stroke in patients with atrial fibrillation. Remarkably, patients treated with dabigatran showed reduced rates of intracerebral hemorrhage compared to warfarin. As the breakdown of endothelial barrier integrity is associated with hemorrhagic events and as thrombin increases endothelial permeability, we hypothesized that dabigatran preserves the endothelial barrier by inhibiting thrombin-induced permeability. We assessed leakage of fluorescein isothiocyanate (FITC)-dextran through the endothelial monolayer and measured trans-endothelial electrical resistance of the endothelial monolayer after treatment of thrombin or thrombin pre-incubated with dabigatran. Thrombin increased the permeability of endothelial cells. Dabigatran effectively blocked the ability of thrombin to increase permeability. Dabigatran inhibited the formation of actin stress fibers induced by thrombin and inhibited consequent destabilization of junctional protein complexes and intercellular gap formation. The interaction of thrombin with protease activated receptor-1 activates the Rho A guanosine triphosphate (GTP)ase-myosin light chain (MLC) phosphorylation signaling axis, leading to actin cytoskeleton changes. This signaling pathway was effectively inhibited by dabigatran in endothelial cells. Consistently, the number of phosphorylated MLC-positive cells was significantly decreased in ischemic tissue of rat brains. These results indicate dabigatran blocks the ability of thrombin to induce vascular permeability and the resulting underlying signaling cascade in endothelial cells. Our findings provide evidence that dabigatran may confer a lower risk of intracerebral hemorrhage by preserving endothelial barrier integrity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Dabigatran inhibits the effect of thrombin to increase endothelial permeability and to change endothelial actin cytoskeleton. </LI> <LI> Dabigatran inhibits thrombin-induced phosphorylation of a regulatory myosin light chain and activation of Rho A. </LI> <LI> Dabigatran may contribute to a lower risk of intracerebral hemorrhage by preserving endothelial barrier integrity. </LI> </UL> </P>