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Amelioration of sepsis by TIE2 activation–induced vascular protection
Han, Sangyeul,Lee, Seung-Jun,Kim, Kyung Eun,Lee, Hyo Seon,Oh, Nuri,Park, Inwon,Ko, Eun,Oh, Seung Ja,Lee, Yoon-Sook,Kim, David,Lee, Seungjoo,Lee, Dae Hyun,Lee, Kwang-Hoon,Chae, Su Young,Lee, Jung-Hoon American Association for the Advancement of Scienc 2016 Science translational medicine Vol.8 No.335
<P>Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsisspecific treatment.</P>
Nuri Tchah(Nuri Tchah ),Donghwa Yang(Donghwa Yang),Heung Dong Kim(Heung Dong Kim),Joon Soo Lee(Joon Soo Lee),Se Hee Kim(Se Hee Kim),Hoon-Chul Kang(Hoon-Chul Kang) 대한소아신경학회 2022 대한소아신경학회지 Vol.30 No.4
Purpose: Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS) is a spectrum of conditions characterized by various phenotypes of cognitive, linguistic, and behavioral regression associated with spike-and-wave activation in sleep. We aimed to investigate the phenotypic spectrum and treatment outcomes of pediatric patients with D/EE-SWAS. Methods: We retrospectively analyzed the medical records of pediatric patients diagnosed with D/EE-SWAS and treated at Severance Children’s Hospital from 2006 to 2022. We extracted information from their medical records on electroencephalography before and after treatment, types of treatment, seizure frequency, and developmental profiles. The primary outcome was reduction of the spike-wave index on electroencephalography after treatment. Results: Twenty-one patients with a median age of 5.3 years (interquartile range, 4.1 to 6.6) at diagnosis were included. Ten patients had delayed development. The patients received various anti-seizure medications. Fourteen received long-term, high-dose steroid therapy, 10 were placed on a ketogenic diet, four received intravenous steroid pulse therapy, and one each was treated with intravenous immunoglobulin and cannabidiol. The most effective treatments were steroid therapy and a ketogenic diet, which were also effective in reducing seizures and improving cognition. Side effects during treatment were transient and treatable. Conclusion: We described the clinical spectrum of pediatric patients with D/EE-SWAS. Steroid therapy and a ketogenic diet can be considered effective therapeutic options for patients with D/EE SWAS.
Effect of annealing temperature on the optical properties of a bulk GaN substrate
Hee Ae Lee,Joo Hyung Lee,Seung Hoon Lee,강효상,Seong Kuk Lee,Nuri Oh,Won Il Park,박재화 한양대학교 세라믹연구소 2020 Journal of Ceramic Processing Research Vol.21 No.5
Variation of optical properties in a bulk GaN substrate have experimentally investigated with respect to different annealingconditions of 700 - 1,000 oC. As-annealed GaN was characterized by scanning electron microscopy, photoluminescence, andRaman spectroscopy. The experimental results demonstrated that the crystallinity and internal residual compressive stress ofGaN are most effectively improved when heat-treated at 900 oC for three hours. The optical characteristics were also improvedby enhancing the quality of the GaN substrate by decreasing both the defect density and the residual stress. It was alsoconfirmed that the effect of the heat treatment was excellent given that impurities were effectively removed by this process.
Encapsulating peritoneal sclerosis in liver transplant recipients
Kyo Won Lee,Chan Woo Cho,Nuri Lee,Sanghoon Lee,Jong Man Kim,Gyu-Seong Choi,Choon Hyuck David Kwon,Jae-Won Joh,Suk-Koo Lee 대한외과학회 2017 Annals of Surgical Treatment and Research(ASRT) Vol.92 No.3
Encapsulating peritoneal sclerosis (EPS) is a rare cause of intestinal obstruction by a thick fibrous membrane wrapping around the small intestine. It is a possible complication after liver transplantation (LT) that can be fatal. This report describes 2 cases of EPS after LT that were successfully treated with surgery, corticosteroids, tamoxifen, and mammalian target of rapamycin inhibitor. After treatment in both cases, the patients were able to start oral feeding and have been symptom free for more than 1 year. These cases suggests that for the management of EPS, surgical treatment is mandatory when the patients present with symptoms of intestinal obstruction or if there are findings suggestive of decreased mural perfusion. Surgery should be accompanied with medical treatment to prevent the relapse of EPS.
Lee, Jung-Eun,Kim, Chan,Yang, Hannah,Park, Intae,Oh, Nuri,Hua, Serenus,Jeong, Haneul,An, Hyun Joo,Kim, Sun Chang,Lee, Gyun Min,Koh, Gou Young,Kim, Ho Min American Association for Cancer Research 2015 Molecular Cancer Therapeutics Vol.14 No.2
<P>Antiangiogenic therapies targeting VEGFA have been commonly used in clinics to treat cancers over the past decade. However, their clinical efficacy has been limited, with drawbacks including acquisition of resistance and activation of compensatory pathways resulting from elevated circulating VEGFB and placental growth factor (PlGF). To bypass these disadvantages, we developed a novel glycosylated soluble decoy receptor fusion protein, VEGF-Grab, that can neutralize VEGFA, VEGFB, and PlGF. VEGF-Grab has the second and third immunoglobulin (Ig)-like domains of VEGF receptor 1 (VEGFR1) fused to IgG1 Fc, with three potential glycosylation sites introduced into the third Ig-like domain of VEGF-Grab by mutagenesis. Compared with VEGF-Trap, VEGF-Grab showed more potent decoy activity against VEGF and PlGF, mainly attributed to the VEGFR1 backbone. Most importantly, the negatively charged <I>O</I>-glycans attached to the third Ig-like domain of VEGFR1 counterbalanced the originally positively charged VEGFR1 backbone, minimizing nonspecific binding of VEGF-Grab to the extracellular matrix, and resulting in greatly improved pharmacokinetic profile. These advancements led to stronger and more durable antiangiogenic, antitumor, and antimetastatic efficacy in both implanted and spontaneous tumor models as compared with VEGF-Trap, while toxicity profiles were comparable with VEGF-Trap. Collectively, our results highlight VEGF-Grab as a promising therapeutic candidate for further clinical drug development. <I>Mol Cancer Ther; 14(2); 470–9. ©2014 AACR</I>.</P>
Nuri Lee,Chan Woo Cho,Jong Man Kim,Gyu-Seong Choi,Choon Hyuck David Kwon,Jae-Won Joh 대한외과학회 2017 Annals of Surgical Treatment and Research(ASRT) Vol.92 No.5
The Glissonian approach, due to its simplicity of procedure, is a technical procedure widely used in open hepatectomy. However, it is not easily applicable in the setting of the total laparoscopic approach because of movement restriction. We herein propose a new and simple method of performing hemihepatectomy by Glissonian approach called temporary inflow control of the Glissonian pedicle (TICGL) technique. Dissection of the Glisson pedicle from the liver parenchyma is done until the posterior margin of the pedicle is visualized, and is clamped with bulldog clamps. Encircling the pedicle is not necessary. Resection of the liver parenchyma is performed under inflow control of the resected side liver providing less bleeding. After sufficient resection is done so that the whole Glissonian pedicle structures are visualized, the pedicle is encircled, often very easily without the fear of bleeding from the posterior side of the pedicle, which is a common problem when encircling is done before parenchymal resection. The staplers may then be applied safely without injuring the major hepatic veins since they have been already exposed. Stapling is done while the tape is retracted toward the contralateral side. This retraction prevents injury or stricture of the contralateral Glissonian pedicle branch. The remnant liver parenchyma is resected and hepatectomy finalized. The TICGL technique provides a safe and easy way of performing major hemihepatectomies, not only by expert laparoscopic surgeons but by less experienced surgeons. It can therefore become a standard method of performing hemihepatectomy by Glissonian approach.
Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma
Lee, Nuri,Lee, Hyewon,Moon, Soo Young,Sohn, Ji Yeon,Hwang, Sang Mee,Yoon, Ok Jin,Youn, Hye Sun,Eom, Hyeon-Seok,Kong, Sun-Young The Korean Society for Laboratory Medicine 2015 Annals of Laboratory Medicine Vol.35 No.6
<P><B>Background</B></P><P>Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM.</P><P><B>Methods</B></P><P>The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR).</P><P><B>Results</B></P><P>Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; <I>P</I>=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (<I>P</I>=0.025). However, no difference was observed in the OS (<I>P</I>=0.428).</P><P><B>Conclusions</B></P><P>Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM.</P>
Lee, Nuri,Kim, Ji-Eun,Gu, Ja-Yoon,Yoo, Hyun Ju,Kim, Inho,Yoon, Sung-Soo,Park, Seonyang,Han, Kyou-Sup,Kim, Hyun Kyung YEAR Wolters Kluwer Health, Inc. All rights reserv 2016 Blood coagulation & fibrinolysis Vol.27 No.1
<P>Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC. Blood Coagul Fibrinolysis 27: 84-89 Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.</P>