• Bulletin of the Korean Chemical Society
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• 제30권10호
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• pp.2309-2317
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• 2009

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

• 생명과학회지
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• 제20권3호
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• pp.453-456
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• 2010

백혈병은 조혈모세포의 비정상적인 증식에 의해 일어나서 질환이고, adenosine deaminase (ADA) 유전자는 백혈병의 약물 작용점으로 중요하다. 이러한 연구의 일환으로 한국인 백혈병 환자 20명의 ADA 유전자의 변이를 조사하기 위해 혈액 genomice DNA를 추출하여 염기서열을 결정하였다. 그 결과 nonsense 변이인 F101F 하나, missense 변이 E260K, D8Y 각각 하나, 그리고 외국에서는 보고되지 않은 것으로 정상인에서 IVS6-52 에 GC가 도입된 것을 확인하였다. 백혈병 환자와 유전자 변이간에 통계학적인 차이점은 없지만 이러한 연구는 앞으로 백혈병의 진단 마크 개발에 도움이 될 것으로 사료된다.

• IMMUNE NETWORK
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• 제11권2호
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• pp.100-106
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• 2011

Background: Disparities of Minor H antigens can induce graft rejection after MHC-matched transplantation. H60 has been characterized as a dominant antigen expressed on hematopoietic cells and considered to be an ideal model antigen for study on graft-versus-leukemia effect. Methods: Splenocytes from C57BL/6 mice immunized with H60 congenic splenocytes were used for establishment of H60-specific CTL clones. Then the clones were characterized for proliferation capacity and cytotoxicity after stimulation with H60. Clone #14, #15, and #23 were tested for the TCR binding avidity to H60-peptide/$H-2K^b$ and analyzed for TCR sequences. Results: H60-specific CTL clones showed different levels of proliferation capacity and cytotoxic activity to H60-stimulation. Clones #14, #15, and #23 showed high proliferation activity, high cytotoxicity, and low activities on both aspects, respectively, and have TCRs with different binding avidities to H60-peptide/$H-2K^b$ with $t_{1/2}$ values of 4.87, 6.92, and 13.03 minutes, respectively. The TCR usages were $V{\alpha}12D-3-01+J{\alpha}11-01$ and $V{\beta}12-1-01+D{\beta}1-01+J2-7-01$ for clone #14, $V{\alpha}13D-1-02+J{\alpha}34-02$ and $V{\beta}13-1-02+D{\beta}2-01+J{\beta}2-7-01$ for clone #15, and $V{\alpha}16D+J{\alpha}45-01$ and $V{\beta}12-1-01+D{\beta}1-01+J{\beta}2-5-01$ for clone #23. Conclusion: The results will be useful for modeling GVL and generation TCR transgenic mouse.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제18권1호
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• pp.153-163
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• 1996

Macrophage inflammatory protein $(MIP)-1{\alpha}$ is a cytokine which produces wide range of bioactivities such as proinflammatory, immunomodulatory, and hematopoietic modulatory actions. To determine whether $MIP-1{\alpha}$ acts as a negative regulator on the functions of lymphocyte, $[^3H]$-thymidine incorporation test and flow cytometric analysis were performed by using human tonsil T cell, human peripheral blood T cell, and murine cytolytic T lymphocyte (CTL) line CTLL-2, The results were as follow. 1. When human tonsil T lymphocytes were stimulated with anti-CD3 monoclonal antibody (mAb), rate of T cell proliferation was about four times increased. 200ng/ml of $MIP-1{\alpha}$ inhibited anti-CD3 mAb-mediated T cell growth as much as 60% (P<0.05). 2. The suppression of human peripheral T cell proliferation produced by $MIP-1{\alpha}$ was dramatic, but variable among T cells derived from different individuals $(40%{\sim}90%)$. 3. $MIP-1{\alpha}$inhibited the proliferation of murine CTL line CTLL-2 as much as 75%(P<0.001). 4. When the $MIP-1{\alpha}$ was added to human peripheral T cell, cell proporation of $CD4^+$ helper T cell and $CD8^+$ CTL were not noticeably affected. The expression level of CD4, not of Cd8, however, was down regulated by $MIP-1{\alpha}$ treatment $(27%{\sim}82%)$.

• 한국약용작물학회지
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• 제19권4호
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• pp.287-299
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• 2011

Pharmacological effects of Panax ginseng have been demonstrated in cardiovascular system, endocrine secretion and immune system, together with antitumor, anti-stress and anti-oxidant activities. Modern scientific data show protective effect of ginseng against bone marrow cell death, increased survival rate of experimental animals, recovery of hematopoietic injury, immunopotentiation, reduction of damaged intestinal epithelial cells, inhibition of mutagenesis and effective protection against testicular damages, caused by radiation exposure. And also, ginseng acts in indirect fashion to protect radical processes by inhibition of initiation of free radical processes and thus reduces the radiation damages. The research has made much progress, but still insufficient to fully uncover the action mechanism of ginseng components on the molecule level. This review provides the usefulness of natural product, showing no toxic effects, as an radioprotective agent. Furthermore, the further clinical trials on radioprotection of ginseng need to be highly done to clarify its scientific application. The effective components of ginseng has been known as ginsenosides. Considering that each of these ginsenosides has pharmacological effect, it seems likely that non-saponin components might have radioprotective effects superior to those of ginsenosides, suggesting its active ingredients to be non-saponin series. These results also show that the combined effects of saponin and non-saponin components play an important role in the radioprotective effects of ginseng.

• 한국방사선학회논문지
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• 제13권3호
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• pp.439-444
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• 2019

본 연구에서는 강력한 항산화제로 알려진 셀레늄의 방사선방호효과를 연구하였다. 렛드에 셀레늄을 14일간 경구투여 후 10 Gy의 방사선을 전신조사하였다. 그리고 1일, 3.5일, 7일, 21일 후에 혈구 성분 및 SOD(Superoxide Dismutase)와 소장의 변화를 관찰하였다. 방사선조사군에 비해 셀레늄 투여 후 방사선조사군에서 조혈면역계의 손상을 경감시키는 유의한 방호 효과가 있었다(p<0.05). 그리고 셀레늄이 항산화 효소인 Superoxide Dismutase(SOD)의 활성을 증가시키는 유효한 성분이며, 방사선 조사에 의한 소장움 세포의 apoptosis 발현을 억제하는 효과가 있음을 확인하였다. 이 결과를 바탕으로 셀레늄은 방사선으로부터 생명체를 보호하는 필수 성분이라 생각한다.

• 생명과학회지
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• 제30권9호
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• pp.826-833
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• 2020

Phospholipase C gamma (PLCγ)는 phosphatidylinositol을 가수분해하여 신호전달 과정에 참여하는 PLC의 주요한 isotype으로 γ-specific array의 특징적인 구조를 바탕으로 receptor tyrosine kinases 및 non-receptor tyrosine kinase 신호를 주로 매개한다. PLCγ1과 PLCγ2의 두 isozyme이 존재하며 다양한 세포에서 발현하여 cell proliferation, migration 및 differentiation 등 여러 세포작용을 조절하고 있다. 최근의 연구들에서 PLCγ 돌연변이가 cancer와 immune disease 및 brain disorder 등에 연관된다는 것이 밝혀지고 있으며 genetic model을 통해 PLCγ의 생리적·병리적 기능이 제시되었다. 본 리뷰에서는 최신의 연구 결과들을 바탕으로 PLCγ의 구조와 활성 조절 기전에 대해 기술하고 나아가 여러 질병의 발병과 진행에서 보고된 PLCγ의 돌연변이와 knockout 마우스를 활용한 연구 결과를 바탕으로 생리적·병리적 관점에서 PLCγ의 역할에 대해 고찰하였다.

• 한국어병학회지
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• 제32권2호
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• pp.59-67
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• 2019

본 연구에서는 넙치(Paralichthys olivaceus)로부터 분리한 바이러스성출혈성패혈증바이러스(viral hemorrhagic septicemia virus, VHSV, genotype IVa)에 대한 단클론 항체(monoclonal antibody, MAb)를 개발하였다. VHSV에 대한 항체를 생산하는 총 5개의 hybridoma clone을 생산하였다. 4개의 MAbs (2C10, 18H4, 23H6, 30B7)는 glycoprotein을 인식하였고, MAb 15E10은 nucleocapsid protein을 인식하였다. 5개의 MAbs는 western blot 상에서 VHSV에 감염된 세포와 넙치시료에 반응하였으나, 정상 세포와 넙치시료에는 반응하지 않았다. 또한 ELISA상에서 VHSV에만 반응하였고 6종의 어류바이러스(IHNV, HIRRV, SVCV, IPNV, MABV, NNV)에는 반응하지 않았다. 이상의 결과, 본 연구에서 제작된 MAbs는 VHSV에만 특이적으로 반응하는 것이 확인되어 VHSV를 검사하는데 사용될 수 있을 것으로 사료된다.

• Reproductive and Developmental Biology
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• 제29권2호
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• pp.69-73
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• 2005

The hematopoietic growth factor erythropoietin (EPO) is required for the maintenance, proliferation, and differentiation of the stem cells that produce erythrocytes. To analyse the biological activity of the recombinant human EPO (rec-hEPO), we have cloned the EPO cDNA and genomic DNA and produced rec-hEPO in the CHO cell lines. The growth and differentiation of EPO-dependent human leukemic cell line (F36E) were used to measure cytokine dependency and in vitro bioactivity of rec-hEPO. MIT assay values were increased by survival of F36E cells at 24h or 72h. The hematocrit and RBC values were increased by subcutaneous injection of 20 IU (in mice) and 100IU(in rats) rec-hEPO. Hematocrit values remarkably increased at $13.2\%$ (in mice) and $12.2\%$ (in rats). The pharmacokinetic behavior with injection of 6 IU of rec-hEPO remained detectable after 24 h in all mice tested. The highest peat appeared at 2h after injection. The long half-life of rec-hEPO is likely to confer clinical advantages by allowing less frequent dosing in patients treated for anemia. These data demonstratethat ree-hEPO produced in this study has a potent activity in vivo and in vitro. The results also suggest that biological activity of ree-hEPO could be remarkably enhanced by genetic engineering that affects the potential activity, including mutants with added oligosaccharide chain and designed to produce EPO-EPO fusion protein.

• Journal of Periodontal and Implant Science
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• 제24권3호
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• pp.472-482
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• 1994

Cytokines expressed specifically in leukocytes subsets and in activated cells, which are involved in chemotaxis and activation of leukocytes, are recently defined as chemokines. Macrophage inflammatory $protein-1{\alpha}(MIP-1{\alpha})$ and $MIP-1{\beta}$ are members of C-C chemokine subfamily which produces wide immunomodulatory, proinflammatory, and hematopoietic modulatory actions. We have studied their gene expression by using Northern blot analysis in various blood cells such as cytolytic T lymphocyte(CTL), helper T lymphocyte(HTL), macrophage, and B lymphocyte. Resting CTL line CTLL-R8 expressed $MIP-1{\alpha}$ mRNA which was downregulated by ConA stimulation. Both of resting and ConA stimulated HTL line Hut78 and Jurkat did not express $MIP-1{\alpha}$ mRNA. There was detectable $MIP-1{\alpha}$ transcript in HTL hybridoma 2B4.11 which was a little upstimulated by ConA stimulation. B cell line 230, and macrophage cell line RAW264.7 and WR19M.1 showed distinct $MIP-1{\alpha}$ message which were induced after LPS stimulation. Expression pattern of $MIP-1{\beta}$ in all cell lines or cell were almost identical to that of $MIP-1{\alpha}$. Also strategies employed to identify and characterize the biological functions was preceded by receptor cloning to trace the shorcut to the final goal of cytokine research. For the cloning of $MIP-1{\alpha}$ receptor(R), we used synthetic oligonucleotides of transmembrane(T) conserved sequences of already cloned human(h) IL-8-R, and performed reverse transcription-polymerase chain reaction(RT-PCR) amplification using murine(m) macrophage cell line mRNA. Among 5RT-PCR products, we isolated a homologous cDNA with hIL-8-R which were shown to be putative mIL-8-R cDNA.