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      • 백혈병 마우스 모델의 동종골수이식에서 활성화된 자연살해세포들의 보충이 이식편대백혈병효과와 이식편대숙주반응에 미치는 영향

        엄현석,한치화,박수정,김소연,정낙균,정대철,진종률,최일봉,양형모,서영훈,송현근,최인표,민우성,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

        배경: 백혈병에서 동종골수이식 (allogeneic bone marrow transplantation)의 성공적 치료 효과를 얻기 위해서는 이식편대숙주반응 (graft-versus-host disease, GVHD) 발생의 극복과 재발의 방지가 중요한 과제이다. 골수를 역류원심성 세포분리 (counterflow centrifugal elutriation, CCE) 방법으로 분리하여 얻은 rotor off (R/O) 세포분획은 T 세포의 수는 적지만 조혈모세포들을 다량 포함하고 있어 동종골수이식에서 주조직적합복합체 (major histocompatibility complex, MHC) 차이를 극복할 수 있고, 이식편의 생착 성공과 GVHD 발생 예방에 효과적이다. 그러나 골수로부터 T 세포를 제거하면 백혈병세포를 공격하는 이식편대백혈병 (graft-versus-leukemia, GVL) 효과가 감소되기 때문에 백혈병 재발의 빈도가 높다. 자연살해세포 (natural killer cell, NK cell)의 보충 첨가는 동종골수이식 후 GVHD 발생을 줄이면서 충분한 GVL 효과를 얻을 수가 있다. 따라서 저자는 분리 후 IL-2로 활성화시킨 NK 세포들을 골수 R/O 세포분획과 함께 백혈병 마우스 모델에 동종이식함으로써 GVHD와 GVL에 미치는 효과를 관찰하였다. 방법: Balb/c (H-2^(d)) 마우스에서 유래된 A20 (murine B-lymphoma/leukemia cell line, H-2^(d)) 백혈병 세포를 이식 2 일 전에 Balb/c 마우스에 주입하고, 치사량의 전신 방사선을 조사한 직후에 Balb/c 또는 C57BL/6 (H-2^(b)) 마우스의 골수 R/O 세포분획을 꼬리정맥을 통하여 주입하였다. 이들은 모두 이식 후 6-8 주 이내에 사망하였다. 동종이식의 대조군 (n=9)에는 1 × 10^(7)의 R/O 세포분획만을 주입하였고, 실험군 (n=9)에는 C57BL/6 마우스의 비장세포들로부터 단클론항체들을 이용한 negative selection방법으로 분리한 후 IL-2로 활성화된 5 × 10^(5)의 NK 세포분획을 1 × 10^(7)의 R/O 세포분획과 함께 주입하였다. GVL 효과의 판정은 이식 후 14 일과 28 일 째 되는 날 마우스에서 골수, 비장, 간 등을 얻어 백혈병 세포들의 침윤을 조직학적으로 관찰하였으며, GVHD의 정도는 육안적 관찰법으로 평가하였다. 결과: R/O 세포분획만을 이식한 대조군의 골수, 비장, 그리고 간 조직에서는 A20 백혈병 세포의 침윤이 각각 89% (8/9), 78% (7/9)와 22% (2/9)에서 관찰되었고, R/O 세포분획과 NK 세포분획을 함께 이식한 실험군에서는 비장과 간을 제외한 골수에서만 89% (8/9)에서 A20 백혈병 세포의 침윤이 관찰되어 두 군 사이에 장기별 분포의 차이를 볼 수 있었다 (P= 0.0001). 한편 GVHD는 두 군 모두에서 경하게 나타나서 유의한 차이는 없었다. 또한 생착 부전으로 사망한 마우스는 없었다. 결론: CCE를 이용하여 T 세포를 제거한 동종골수이식에서 NK 세포의 보충은 GVHD의 악화는 일으키지 않으면서, 백혈병의 진행을 억제하는 GVL 효과를 얻을 수 있었다. Background: Allogeneic bone marrow transplantation (BMT) with T cell-depleted marrow accompanies engraftment failure and relapse of leukemia by a loss of the graft-versus-leukemia (GVL) effect frequently, while it can prevent GVHD. Supplement of NK cells could prevent GVHD and enhance GVL effect in several murine allogeneis BMT models Roter off (R/O) cell fraction obtained by counterflow centriation elutriatio (CCO) contains small number of T cells and many hematopoietic stem cells. The aim of this study was to determine the effect of R/O cell fraction supplemented with IL-2 activated NK cells on GVL and GVHD within the leukemic mouse BMT model. Methods: Inoculation of A20 (H-2d, murine B-lymphoma/leukemia, Balb/c origin) cells into Balb/c mice via the tail vein 2 days prior to lethal total body irradiation (TBI) and infusion of the Balb/c BM or C57BL/6 (H-2b) R/O fraction were performed. It resulted in 100% mortality within 6 to 8 weeks. The irradiated mice in the control group were injected with 1 × 107 R/O cell fraction alone (n=9) and in the experimental group mice were injected with 1 × 107 R/O cell fraction plus 5 × 105 negatively selected IL-2 activated NK cell fractions of the spleens via the tail vein (n=9). On day 14 and 28 after BMT, the bone marrows, spleens, and livers of mice were harvested for histopathologic analysis of the infiltrations of leukemic cells. We then evaluated the GVHD within the mice. Results: A histopathologic study of the recipients receiving R/O fraction alone showed infiltration of leukemic cells, 89% (8/9) in bone marrows, 78% (7/8) in spleens, and 22% (2/9) in livers. The experimental group of mice showed only the infiltration of leukemic cells 89% (8/9) in bone marrows, not in spleens and livers. There were the organ differences of the leukemic cells infiltrations between the two groups (P=0.0001). There were no obvious differences in the GVHD scores between these two groups, and severe GVHD was not observed. There was no engraftment failure among groups. Conclusion: Thus, our findings suggest that R/O cell fraction obtained by CCE and supplemented with NK cells can promote GVL effect without mediating clinically overt GVHD in allogeneic BMT of mouse leukemia.

      • KCI등재

        Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells

        Lee, Young-Sun,Yi, Hyon-Seung,Suh, Yang-Gun,Byun, Jin-Seok,Eun, Hyuk Soo,Kim, So Yeon,Seo, Wonhyo,Jeong, Jong-Min,Choi, Won-Mook,Kim, Myung-Ho,Kim, Ji Hoon,Park, Keun-Gyu,Jeong, Won-Il Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.11

        Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

      • SCISCIESCOPUS

        Adiponectin is a negative regulator of NK cell cytotoxicity.

        Kim, Kun-Yong,Kim, Jae Kwang,Han, Seung Hyun,Lim, Jong-Seok,Kim, Keun Il,Cho, Dae Ho,Lee, Myeong-Sok,Lee, Jeong-Hyung,Yoon, Do-Young,Yoon, Suk Ran,Chung, Jin Woong,Choi, Inpyo,Kim, Eunjoon,Yang, Young American Association of Immunologists 2006 Journal of Immunology Vol.176 No.10

        <P>NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-kappaB activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.</P>

      • KCI등재

        심혈관계질환으로 사망한 성인형다낭신 3예 보고

        양경무,권일훈,조갑래,서중석 大韓法醫學會 1999 대한법의학회지 Vol.23 No.1

        Adult polycystic kidney disease is a genetic disease characterized by bilateral multiple renal cysts and is transmitted as an autosomal dominant traits. The disease usually manifests in the fourth decade of life. The affected patients usually die with end stage renal failure, cardiovascular assaults and infection etc. Cardiovascular assaults include ruptured berry aneurysm, spontaneous intracranial hemorrhage, acute myocardial infarction, dissecting aortic aneurysm and hypertensive heart failure. Fatal intracranial hemorrhage and hypertensive heart failure occur in 15% and 2% of patients, respectively. Genetically-dater-mined structural weakness in the arterial wall have been suggested as a possible factor in the genesis of berry aneurysm. We have experienced three autopsy cases with cardiovascular causes of sudden death. Two cases have intracranial hemorrahage (1 berry aneurysm and 1 intracerebral hemorrhage) and the remaining one is dead with hypertensive cardiomyopathy. All of them are aged over 40 years and associated with polycystic liver disease. Histologically, myriad cysts of enlarged bilateral kidney are lined by single layer of cuboidal cells with focal hyperplastic epithelial configuration. Diffusely scattered liver cysts are also lined by flat to cuboidal epithelium and often associated with portal fibrosis.

      • KCI등재

        기계적 합금화에 의해 제조된 고규소 Al-Si 합금 나노 결정의 특성

        이정일,김일호,홍태환,어순철,양계준,석현광,한만갑,최국선,김준수 대한금속재료학회 2003 대한금속·재료학회지 Vol.41 No.7

        High silicon Al-Si alloys with nanocrystalline structures have been produced by mechanical alloying process. Microstructural changes of the Al-Si alloys were investigated by scanning electron microscopy and the transmission electron microscopy. X-ray diffraction analysis was also made to characterize the lattice constant, crystallite size and misfit strain. It was found that the effective milling time by attrition milling was about 12hours for Al-70 wt%Si alloy system. The Al and Si crystallites were reduced to about 30 nm and 70 nm, respectively, by the mechanical alloying for more than 12hours. The misfit strains increased with milling time UD to 240 hours, and saturated to 5.73×10^(-3) for Al and Si crystallites, respectively.

      • DNA回復에 미치는 Poly(ADP-ribose)의 影響에 관한 硏究

        金碩煥,鮮于洋一 東亞大學校 1990 東亞論叢 Vol.27 No.1

        Effects of 3-aminobenzamide(3-AB), a potent inhibitor of poly(ADP-ribose) polymerase, on DNA replication was determined in CHO cells treated with methyl methanesulfonate(MMS) or UV-light by alkaline s ucrose gradient sedimentation analysis. MMS has been thought to inhibit the replication intitiation in mammalian cells, but we could also observe the inhibitory effect on chain elongation in CHO cells. At low concentration of 3-AB, the rate of DNA replication was not inbibited but at high concentration was shown in dose dependent manner. When MMS-treated cells were subsquently exposed to 3-AB, additive ingibitory effects were brought out. this result may be due to increases of single stand breaks by 3-AB. In the case of treatment with UV-light and 3-AB, hihg concentration of 3-AB induced the additive inhibitory effect on DNA replication, but low concentration of 3-AB alleviated unexpectedly the inhibitory effects of UV-light alone.

      • 육우 비선호 부위를 활용한 육우햄의 품질특성

        이주호, 최정석, 정준영, 최양일 忠北大學校 農業科學硏究所 2012 農業科學硏究 Vol.28 No.3

        This study was undertaken to compare the quality characteristics of dairy beef ham. Dairy beef hams were manufactured using non-preferred portion (top round). 5 treatments were prepared: T1(beef 50% + pork emulsion 50%), T2(beef 65%emulsion 35%), T3(beef 80%emulsion 20%), T4(beef 90%emulsion 10%), T5(beef 100%emulsion 0%). In chemical composition, dairy beef content increases, moisture content was increased, fat content was decreased. In the meat quality characteristics, T5 showed higher (p<0.05) water holding capacity value than the others. Dairy beef content increases, product loss and cooking loss were decreased. In hunter color, dairy beef content increases, redness was increased. In texture profile analysis, T4 and T5 were significantly higher than the others. As a result, dairy beef ham with 80~90% dairy beef and 10~20% pork emulsion has low fat content, high product yield and superior texture profile, which could be developed as a dairy beef hams using non-preferred portion.

      • 송아지고기 소시지와 시중에 판매되는 우육과 돈육 소시지 제품의 저장특성 비교

        이주호, 최정석, 이현진, 정구용, 최양일 忠北大學校 農業科學硏究所 2013 農業科學硏究 Vol.29 No.1

        This study was undertaken to compare the storage characteristics between veal sausage and commercial pork and beef sausages in Korean domestic market. We manufactured 3_types of sausages and purchased 2_types of sausages in the market: T1(B-company product), T2(O-company product) and we made T3(smoked veal sausage), T4(smoked veal sausage with pepper) and T5(cooked veal sausage) products. During 20 days of storage at 4oC, T5 showed significantly higher in TBA value and VBN value (p<0.05). But TBA and VBN values showed normal range in all products. T3, T4, and T5 showed higher total microbial count than T1 and T2 (p<0.05). According to the result, beef and pork sausages in the market showed different total microbial count and VBN values from those made in laboratory. This result could be come from the different additives used and manufacturing processes. However, all products can be stored up to 20 days in the cooler.

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