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      • KCI등재

        악하선에서 분리된 NGF에 의해 유도되는 비만세포 활성화에 미치는 상백피의 억제효과

        정홍주,백병주,김대범 大韓小兒齒科學會 1993 大韓小兒齒科學會誌 Vol.20 No.2

        Cortex Mori(Norus alba L), the root bark of mulberry tree has been used as an antiphlogistic, diuretic, and expectorant in herbal medicine. Previous studies have demonstrated that Cortex Mori had inhibitory effects on the compound 48/80-induced degranulation and histamine release from rat peritoneal mast cells(RPMC). The purpose of this study is to determine whether Cortex Mori(CM) could inhibit the nerve growth factor(NGF)-induced activation of RPMC in vivo and in vitro. In vitro, various concentrations of NGF(0.1, 1, 10 and 100㎍/ml) were added into the RPMC suspension(??cells/ml) pretreated with lyso-PS at 37℃ for 10minutes. Cortex Mori pretreatment was performed before or after lyso-PS treatment at 37℃ for 10minutes. Histamine in the supernatants and calcium uptake of RPMC were measured by radioisotope enzymatic histamine assay and radioisotope calcium uptake method. In vivo experiment, to estimate the effect of Cortex Mori on NGF-induced cutaneous reaction, various doses of NGF with or without Co rtex Mori on NGF-induced cutaneous reaction, various doses of NGF with or without Cortex Mori were injected i.d. int the shaved flank of Sprague-Dawley rats, and the blue cutaneous staining induced by Evans’blue injection at the NGF alone Cortex Mori plus NGF injection sites were observed. Results were 1) the NGF-induced degranulation and histamine release of RPMC pretreated with Cortex Mori were significantly inhibited, compared to those of control without Cortex Mori pretreatment,2) Cortex Mori inhibited the NGF-induced cutaneous reaction remarkably. From the above results, it is suggested that Cortex Mori contains some substances with an activity to inhibit the NGF-induced activation of mast cell.

      • KCI등재
      • SCIESCOPUS

        Arterioportal shunt incidental to treatment with oxaliplatin that mimics recurrent gastric cancer

        Kim, Hong-Beum,Park, Sang-Gon WJG Press 2017 WORLD JOURNAL OF GASTROENTEROLOGY Vol.23 No.33

        <P>Arterioportal shunt (APS) is an organic communication between the hepatic arterial system and the portal venous system. The APS is one of the major causes of transient hepatic attenuation differences on dynamic computed tomography (CT) or magnetic resonance imaging (MRI). This condition is usually associated with trauma, liver cirrhosis, and malignancies of the liver. However, there has been no report about oxaliplatin-induced APS. A 41-year-old male was diagnosed with Stage IIIB gastric cancer. The patient initially underwent neoadjuvant chemotherapy with capecitabine and oxaliplatin After 3 cycles of therapy, the mass had markedly decreased, and a total gastrectomy with splenectomy was performed. Since the malignancy was locally invasive, the patient was continued on the same regimen of the adjuvant chemotherapy. After 3 more cycles, a computed tomography revealed a 1 cm sized arterial-enhancing nodule in the right lobe of the liver. An MRI revealed an arterial enhancing lesion, and a positron emission tomography CT scan showed a hypermetabolic lesion in the same portion of the liver. We tried to perform a liver biopsy; however, an ultrasonography could not detect any mass. A presumptive diagnosis of an APS due to a recurred cancer was made. We found a similar but slightly different case report of an oxaliplatin-induced liver injury, mimicking a metastatic tumor on an MRI. Based on a prior report, the patient was continued on treatment with adjuvant chemotherapy following discontinuation of oxaliplatin. After 2 cycles, the arterial enhancing liver mass resolved, supporting the final diagnosis of an APS, related to oxaliplatin-induced sinusoidal injury. The patient has not experienced any a relapse after two years of additional follow up recurrent gastric cancer upon interpretation of multiple imaging modalities.</P>

      • KCI등재

        APEX-1 Regulates Cell Proliferation through GDNF/ GFRα1 Signaling

        Hong-Beum Kim(김홍범),Gurusamy Hariharasudhan(구루사미 하리하라수단),Cha-Kyung Youn(윤차경) 한국생명과학회 2013 생명과학회지 Vol.23 No.10

        APEX-1 (인간 apyrimidinic / apurinic 효소)은 염기성 사이트 및 DNA단일 가닥 결손으로 손상된 DNA을 복구 할 수 있는 다기능 단백질이다. 또한 APEX-1은 많은 전사 인자들의 redox-modifying factor (산화 환원 수정 요소)로서의 역할을 한다고 알려져 있다. 이런 APEX-1의 전사 타겟을 동정하는 것은 APEX-1의 다양한 세포 내 작용 메커니즘을 이해하는데 필수적이다. 따라서 이 논문에서는 먼저 Expression array analysis를 통해 glial cell-derived neurotropic factor receptor α1 (GFRα1)을 동정하였다. GFRα1은 glial cell-derived neurotropic factor (GDNF) family 수용체이며 APEX-1에 의해 발현이 증가된다. APEX-1이 과발현된 세포에서 GDNF처리에 의해GDNF/ GFRα1 시그널 타겟인 c-Src가 Tyr418잔기에서 인산화 됨을 관찰하였다. 또한 APEX-1이 과발현된 세포에 GDNF처리하면, 세포증식이 증가함을 보았다. 반면, APEX-1 발현을 siRNA을 이용하여 감소시키면 GFR α1 발현과 GDNF에 의한 c-Src 인산화 및 세포증식이 감소함을 확인하였다. 이상의 결과는 APEX-1은 GDNF/GFRα1 시그널을 통해 세포 생존과 증식을 조절함을 증명하였다. 따라서 본 연구를 통해 APEX-1의 세포 증식을 조절하는 새로운 기전을 규명하였다. Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor α1 (GFRα1), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/GFRα signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the GFRα1 expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/GFRα signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.

      • Improvement of gas Transfer by Hemosome

        Kim, Gi-Beum,Hong, Chul-Un,Kim, Jin-Shang,Kim, Min-Ho,Kang, Hyung-Sub SAGE Publications 2010 The International journal of artificial organs Vol.33 No.3

        <P>Intravascular oxidation is a respiratory assist method used to treat acute respiratory distress syndrome (ARDS). However, intravascular oxidation through higher gas exchange is needed for successful clinical applications. In this study, an attempt was made to improve the gas exchange of an intravascular lung assist device by decreasing the level of damage to the blood through the microencapsulation of hemoglobin. The results showed that a hemosome 0.8 microm in diameter could be produced by microencapsulating the hemoglobin extracted from fresh bovine blood with the phospholipids extracted from egg yolk. The oxygen saturation curve of hemosome was S-shaped, which is similar to that found in normal blood, and the P50 was 24 mmHg. The oxygen saturation in the mixed solution of hemosome and blood at a 1:4 (v/v%) ratio was similar to that of normal blood. The gas exchange of the blood-hemosome mixed solution was more effective than whole blood. Therefore, the hemosome solution is expected to improve oxygen transfer.</P>

      • SCISCIESCOPUS

        Ape1/Ref-1 Induces Glial Cell-Derived Neurotropic Factor (GDNF) Responsiveness by Upregulating GDNF Receptor α1 Expression

        Kim, Mi-Hwa,Kim, Hong-Beum,Acharya, Samudra,Sohn, Hong-Moon,Jun, Jae Yeoul,Chang, In-Youb,You, Ho Jin American Society for Microbiology 2009 Molecular and cellular biology Vol.29 No.8

        <B>ABSTRACT</B><P>Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) dysregulation has been identified in several human tumors and in patients with a variety of neurodegenerative diseases. However, the function of Ape1/Ref-1 is unclear. We show here that Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor (GDNF) receptor α1 (GFRα1), a key receptor for GDNF. Expression of Ape1/Ref-1 led to an increase in the GDNF responsiveness in human fibroblast. Ape1/Ref-1 induced <I>GFRα1</I> transcription through enhanced binding of NF-κB complexes to the <I>GFRα1</I> promoter. GFRα1 levels correlate proportionally with Ape1/Ref-1 in cancer cells. The knockdown of endogenous Ape1/Ref-1 in pancreatic cancer cells markedly suppressed GFRα1 expression and invasion in response to GNDF, while overexpression of GFRα1 restored invasion. In neuronal cells, the Ape1/Ref-1-mediated increase in GDNF responsiveness not only stimulated neurite outgrowth but also protected the cells from β-amyloid peptide and oxidative stress. Our results show that Ape1/Ref-1 is a novel physiological regulator of GDNF responsiveness, and they also suggest that Ape1/Ref-1-induced GFRα1 expression may play important roles in pancreatic cancer progression and neuronal cell survival.</P>

      • KCI등재

        Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer

        Hong-Beum Kim,Won Jin Cho,Nam Gyu Choi,Sung-Soo Kim,Jun Hee Park,Hee-Jeong Lee,Sang Gon Park 대한외과학회 2017 Annals of Surgical Treatment and Research(ASRT) Vol.92 No.1

        Purpose: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer Methods: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. Results: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC50 of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. Conclusion: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.

      • KCI등재

        A Study of Design of Hollow Fiber Membrane Modules for using in Artificial Lung by the PZT Actuator

        Kim, Gi-Beum,Kim, Seong-Jong,Hong, Chul-Un,Lee, Yong-Chul,Kim, Min-Ho The Korean Society of Medical and Biological Engin 2006 의공학회지 Vol.27 No.4

        The purpose of this work was to assess and quantify the beneficial effects of gas exchange, while testingto the various frequencies of the sinusoidal wave that was excited by the PZT actuator, for patients suffering from acute respiratory distress syndrome (ARDS) or chronic respiratory problems. Also, this paper considered a simulator to design a hollow type artificial lung, and a mathematical model was used to predict a behavior of blood. This simulation was carried out according to the Montecarno's simulation method, anda fourth order Runge-Kutta method was used to solve the equation. The experimental design and procedure are then applied to the construction of a new device to assess the effectiveness of the membrane vibrations. As a result, the vibration method is very effective in the increase of gas transport. The gas exchange efficiency for the vibrating intravascular lung assist device can be increased by emphasizing the following design features: consistent and reproducible fiber geometry, and most importantly, an active means of enhancing convective mixing of water around the hollow fiber membranes. The experimental results showed the effective performance of the vibrating intravascular lung assist device. Also, we concluded that important design parameters were blood flow rates, fiber outer diameter and oxygen pressure drop. Based on the present results, it was believed that the optimal level of blood flow rates was 200$cm^3$/min.

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