• 제목/요약/키워드: blockade

검색결과 461건 처리시간 0.024초

Blockade of Vascular Endothelial Growth Factor (VEGF) Aggravates the Severity of Acute Graft-versus-host Disease (GVHD) after Experimental Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

  • Kim, Ai-Ran;Lim, Ji-Young;Jeong, Dae-Chul;Park, Gyeong-Sin;Lee, Byung-Churl;Min, Chang-Ki
    • IMMUNE NETWORK
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    • 제11권6호
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    • pp.368-375
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    • 2011
  • Background: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. Methods: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of $B6\;(H-2^b)\;{\rightarrow}B6D2F1\;(H-2^{b/d})$. Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 ($50{\mu}g/dose$) or control diluent every other day for 2 weeks (total 7 doses). Results: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor $CD3^+$ T cells on day +7 compared to control treated animals. The donor $CD4^+$ and $CD8^+$ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. Conclusion: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.

회야강 하구방사제 건설에 따른 진하해수욕장 해안선 변화분석 및 예측 (Coastline Evolution Analysis and Forecast due to the Construction of Groin at Heoya-River Mouth Area)

  • 김성득;강경호;박해성
    • 한국해양공학회지
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    • 제22권2호
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    • pp.28-33
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    • 2008
  • From the 1997 to January, 2004, a groin 156m long was constructed at the mouth of the Heoya river-mouth as a protection and barrier. To understand the changes to Jinha beach from the blockade of the river mouth, several aerial photographs, etc., were compared, which showed that the changes were significant. Comparing these results to the state of the area before construction of the groin, the blockade of the river was relaxed, but the formation of the tombolo, in the middle groin area was accelerated and the total Jinha beach erosion and especially the erosion of the southern part of Jinha beach was developed. But according to statements by residents and some current documents, the blockade of the Heoya-river mouth is still underway at the surrounding areas of the groin and chronic dredged sand has been used for littoral nourishment at the northern part of the middle groin and on Jinha beach. The result of numerical simulation based on the present state shows that if this sort of dredging is stopped, the sand accumulation will progress near the river mouth groin and the existing tombolo at the middle groin will progress to the north and severe erosion will occur at the southern coastline near the middle groin and the farthest southern part of Jinha beach, and Jinha beach itself will experience a gradual erosion. The main reason for these erosions should be the typhoons that are happening during the summer season. To provide protection from these kinds of undesirable erosions, a total of 23 numerical simulations have been done. It has been shown that submerged breakwaters at the front area of the beach will be efficient to protect from main beach erosion, but there should be alternative proposals for the influence of the river mouth blockade.

Repression of the F-box protein Skp2 is essential for actin damage-induced tetraploid G1 arrest

  • Jo, Yongsam;Shin, Deug Y.
    • BMB Reports
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    • 제50권7호
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    • pp.379-383
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    • 2017
  • We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was reduced, but p27/Kip1 was increased, after actin damage-induced cytokinesis blockade. The role of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and ultimately, induction of apoptosis. These results suggest that Skp2 repression is important for sustaining tetraploid G1 arrest after cytokinesis blockade and is required to prevent uncoupled DNA replication and nuclear division without cytokinesis.

Optimising IL-2 for Cancer Immunotherapy

  • Jonathan Sprent;Onur Boyman
    • IMMUNE NETWORK
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    • 제24권1호
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    • pp.5.1-5.19
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    • 2024
  • The key role of T cells in cancer immunotherapy is well established and is highlighted by the remarkable capacity of Ab-mediated checkpoint blockade to overcome T-cell exhaustion and amplify anti-tumor responses. However, total or partial tumor remission following checkpoint blockade is still limited to only a few types of tumors. Hence, concerted attempts are being made to devise new methods for improving tumor immunity. Currently, much attention is being focused on therapy with IL-2. This cytokine is a powerful growth factor for T cells and optimises their effector functions. When used at therapeutic doses for cancer treatment, however, IL-2 is highly toxic. Nevertheless, recent work has shown that modifying the structure or presentation of IL-2 can reduce toxicity and lead to effective anti-tumor responses in synergy with checkpoint blockade. Here, we review the complex interaction of IL-2 with T cells: first during normal homeostasis, then during responses to pathogens, and finally in anti-tumor responses.

척추경막외 병용마취시 경막외강으로 주입된 생리식염수와 부피바카인의 감각차단 범위에 대한 효과 (Effects of Saline and Bupivacaine for Epidural Top-up on Sensory Blockade Level during Combined Spinal Epidural Anesthesia)

  • 김동연;한종인
    • The Korean Journal of Pain
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    • 제13권1호
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    • pp.84-88
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    • 2000
  • Background: An increase in the maximum level of sensory blockade (MLSB) following an epidural top-up in combined spinal epidural anesthesia (CSE) may be achieved by a volume effect as the volume of local anesthetic compresses the dural sac, by a local anesthetic effect, or by a combination of both effects. This study was conducted to investigate the contribution of each of these effects. Methods: Sixty patients scheduled for lower limb surgery under CSE were randomly allocated to one of three groups of twenty patients each. Using the needle-through needle technique, all patients received a subarachnoid dose of 10 mg hyperbaric 0.5% bupivacaine. At 30 min after subarachnoid injection, an epidural top-up with saline 10 ml (group II) or 0.5% bupivacaine 10 ml (group III) was administered; patients in group I received no epidural top-up. The level of sensory blockade was assessed at 5, 10, 15, 20, 25, 30 min after subarachnoid injection and at 5, 10, 15, 20, 25, 30 min after epidural top-up. Results: There was no significant difference in the MLSB and the onset time of MLSB among group I-III. Conclusions: We concluded that the epidural top-up with saline 10 ml or 0.5% bupivacaine 10 ml which injected at 30 min after subarachnoid injection did not significantly increase the level of subarachnoid block in lower extremity surgical patients.

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Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

  • Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Jacob, Omar;Orellana, Nelson
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6615-6619
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    • 2015
  • Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

봉쇄와 보안장비 수준 기반 정보보호 위험관리 수준 측정 연구 (A study for Cybersecurity Risk Management by Blockade and Defense Level Analysis)

  • 한충희;한창희
    • 정보보호학회논문지
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    • 제31권6호
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    • pp.1261-1266
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    • 2021
  • 기존의 정보보호 위험평가 방법은 정보자산의 취약성을 평가하는데 중점을 둔다. 그러나 정보자산의 형태가 바뀌고 새로운 유형의 정보자산이 나오면 그에 대한 평가기준도 추가하거나 삭제하는 등의 보완을 거쳐야 하는 한계가 있다. 기존 방법들은 사이버 위협이 유입되는 경로에 연구가 미흡하다. 특히, 공인 IP를 가지고 있는 웹기반 정보시스템을 대상으로 유입되는 유입경로의 봉쇄를 위한 연구가 매우 부족한 상황이다. 이에 본 논문에서는 BDLA (Blockade and Defense Level Analysis) 기반 정보보호 위험평가 모델의 주요 연구내용을 소개 한다. 또한, BDLA기반 정보보호 위험평가 모델을 적용하여 17개 공공기관의 봉쇄수준과 보안장비 수준 측정을 통하여 정보보호 위험 수준을 연구하였다.

Zooplankton and Phytoplankton Dynamics with the Construction of River Mouth Dam in Kum River Estuary, Korea

  • Kim, Say-Wa;Han, Myung-Soo;Lee, Kyung;Choi, Young-Kil;Yoo, Kwang-Il
    • 생태와환경
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    • 제35권2호통권98호
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    • pp.141-144
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    • 2002
  • The construction of river mouth dam has prevented seawater from backwarding to upstream in Kum river estuary since 1990. Field observation on environmental factors, and zooplankton and phytoplankton dynamics have been carried out three times with two month interval in the summer and autumn in 2000 at three selected stations in Kum river estuary. Blockade of seawater flowing backward to upstream caused sharp contrast of zooplankton fauna and phytoplankton flora between upstream and downstream of the river mouth dam. Freshwater cladocerans i.e., Bosmina longisrostris and Daphnia galeata dominated in the upstream, and marine copepods of Acartia omorii and Paracalanus crassirostris occurred abundantly in downstream of the dam. Freshwater diatoms did not distributed in the downstream of the dam except Melosira varians, while marine diatom of Cylidrotheca closterium occurred in benthic waters bath in upstream and downstream of the dam. The construction of the river mouth dam seems to play an ecological role to blockade the input of marine organism into the upstream in Kum river estuary.

Scopolamine으로 유도된 콜린성 신경계 차단 동물모델에서 포공영(Taraxacum platycarpum) 추출물의 기억력 개선효과 (Ameliorating Effect of Taraxacum platycarpum Extract in the Scopolamine-induced Cholinergic Blockade Mouse Model)

  • 권유빈;박호재;신범영;류종훈
    • 생약학회지
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    • 제48권2호
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    • pp.119-124
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    • 2017
  • Taraxacum platycarpum H. Dahl. (Compositae) has been used as an anti-inflammatory or anti-cancer agent in the clinic. Although its antidepressant effect has been reported, however, its cognitive function is not investigated until yet. In the present study, we investigated whether the water extract of T. platycarpum (WETP) could improve cognitive function in cholinergic blockade-induced amnesia mouse model using the passive avoidance or Y-maze task. WETP (12.5, 25 or 50 mg/kg) significantly ameliorated the scopolamine-induced cognitive impairment both in the passive avoidance test and the Y-maze test. In addition, WETP significantly inhibited acetylcholinesterase (AChE) activity measured by an ex vivo study using the mouse whole brain. These results suggest that WETP alleviates the cognitive dysfunction caused by the cholinergic blockade, in part, via AChE inhibition, and that it may be a useful for treating cognitive dysfunction.

봉쇄-탐지-대응 기반 보안관제 대시보드 설계 (Security Operation Dashboard Design by Blockade-Detection-Response)

  • 한충희
    • 융합보안논문지
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    • 제21권3호
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    • pp.39-47
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    • 2021
  • 효율적인 보안관제센터 운영을 위해서는 보안관제 대시보드의 표준화가 반드시 필요하다. 보안관제 대시보드는 24시간 365일 내내 함께 생활해야 하는 보안관제근무자들에게 많이 활용되도록 구성해야 한다. 또한 보안관제센터의 업무활동을 종합적으로 표출할 수 있어야 한다. 추가적으로 보안관제센터의 업무활동들을 쉽게 설명할 수 있어야 할 것이다. 이에 본 논문에서 사례기관에 실제 적용한 봉쇄·탐지·대응 기반의 보안관제 대시보드 디자인을 설명하고자 한다. 이를 통해 불필요한 귀빈 맞춤형 대시보드 구성작업에 대한 노력과 시간을 줄이고 보안관제센터의 효율적인 운영에 이바지하고자 한다.