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새로운 간염치료제인 수용성 DDB 유도체 (DDB-S)의 항원성 평가
한형미,김진호,최경백,김형수,정승태,문전옥,이치호,김주일,Han, Hyung-Mee,Kim, Jin-Ho,Choi, Kyoung-Baek,Kim, Hyung-Soo,Chung, Seung-Tae,Moon, Jeon-Ok,Lee, Chi-Ho,Kim, Joo-Il 한국독성학회 1998 Toxicological Research Vol.14 No.3
Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.
M3S Tumor Necrosis Factor-$\alpha$(M3S TNF)의 항원성
한형미,손경희,오현정,최경백,정승태,선우연,신남규,신항철 한국독성학회 1997 Toxicological Research Vol.13 No.3
The antigenic potential of M3S tumor necrosis factor-$\alpha$(M3S TNF), which is a mutated form of TNF(TNF mutein) designed to reduce adverse effects of wild type human TNF, was investigated in the present study. The antigenicity of M3S TNF was examined by conducting active systemic anaphylaxis (ASA) test in guinea pigs, heterologous(mouse-rat) passive cutaneous anaphylaxis(PCA) test and passive hemagglutination(PHA) test. The experimental animals were divided into low, medium, high and the highest dose groups and the groups with or without immunoadjuvant, sensitized according to the appropriate schedule and challenged. In ASA test, when challenged with 120 $\mu\textrm{g}$ /animal, moderate to severe positive anaphylactic responses were observed in groups sensitized with 12 $\mu\textrm{g}$ /animal, 120 $\mu\textrm{g}$ /animal and 120 $\mu\textrm{g}$ /animal+Freund's complete adjuvant. In PCA test, positive responses were observed in the group sensitized with the highest dose emulsified with an alum(12 $\mu\textrm{g}$ /animal+alum). In PHA test, positive responses were observed in the group sensitized with 3 $\mu\textrm{g}$ /animal emulsified with an alum. All the other groups in each experiment showed negative responses. Based on these results, M3S TNF is considered to have some antigenic potential.
Sodium arsenite가 골수세포의 분화에 미치는 영향(Ⅰ)
정혜주,박재현,김영옥,정승태,김진호,한성수,최경백,이미옥,조대현 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-
비소화할물의 골수독성 여부를 알아보기 위하여 골수세포의 분화 준간단계에서 생성되는 myeloid계 colony인 CfU-GM(gianulocytejmacrophage-colony forming unit)의 형성 정도를 관찰하였다.BALB/c 마우스에 NaAs02(2.5 또는 10 rg/mouse/day)를 각각 14일간 경구투여한 후 체중변화율 및 말초혈액의 혈액학적 검사를 실시귀였으며 투옥종료 24시간 후 마우스 대퇴골로부터 분리한 골수세포를 7일간 배양하여 생성된 CFU-GM을 계수하몄다. 비소화함물의 투여는 체중변화율 및 혈액학적 지표에 별다른 영향을 주지 않았으나 CFU-GM은 10μg NaA302/day 투여군에서 대의군에 비괘 140%의 형성 증가를 나타내펐다. 마우스 대퇴골로부터 분리한 골수세포에 NaAs02(0.03,0.3,0.6,1,3,5,10 #M)를 처리하고 T일간 배양 후 CFU-GM 형성 정도를 측정한 결과 0.6μM이하의 농도에서는 대조군에 비해 별다른 변화가 없었으나 그 이상의 농도애서는 점차 감소되어 10μM 농도에서는 거의 100% 저해되었다. 세포생쫀율 시헴결과 10μM에서의 CFU-GM 형성을 억제는 세포독성에 의한 것으로 사료되며 NaAsO₂는 1-5μM에서 특이적 CFU-GM 형성을 억제하엿다. 이상의 결과를 종합할때 비소는 골수세포가 myeloid 계열로의 분화함에 영향을 미칠 수 있으며 이러한 영향은 비소의 노출 농도와 상관성이 있는바 비소의 위해 가능성에 대한 포괄적 연구가 필요함을 시사하고 있다. To evatuate toxic potentiat of arsenic compound on proliferation of bone marrow sodivm arsenite(0.125 and 0.5 mg/kg/day) were administered orally to Balb/c mice forrow cell changesin blood001) atin oifro, no changes occurred in numbers ofM, however, the numbers of CFU-GM werecytotoxicitf. These results indicate thaa sodium arsenite could affect rnyeloid profhematopoietic progenitor cells.
종양괴사인자(TNF)가 ME-180 사람 경부 암종세포에서 종양 발생 유전자의 발현에 미치는 영향
한형미(Hyung Mee Han),김형수(Hyung Soo Kim),손경희(Kyung Hee Sohn),최경백(Kyoung Baek Choi),정승태(Seung Tae Chung),김진호(Jin Ho Kim),이병무(Byung Moo Lee),김주일(Joo Il Kim) 大韓藥學會 1997 약학회지 Vol.41 No.5
Tumor necrosis factor-alpha (TNF) induced a cytotoxic response in ME-180 cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of mitogenic stimuli : increased c-fos, c-jun and jun-B expression. Depletion of protein kinase C (PKC) by exposure of ME-180 cells to 100ng/ml phorbol myristate acetate (PMA) for 24hours almost completely abolished TNF-mediated increase in these signals, indicating that a PKC-dependent pathway is involved in TNF-mediated increases in the expression of c-fos, c-jun and jun-B. Characteristics of TNF receptors after exposure to 100ng/ml PMA or 24hours were not altered, suggesting that diminished induction of these oncogenes by TNF after PMA treatment is not due to any changes at the receptor level. To examine whether a PKC-dependent pathway is involved in TNF-mediated cytotoxicity in ME-180 cells, cytotoxicity was measured after depletion of PKC. No apparent changes in cytototoxicity after PKC depletion suggest that a PKC-dependent pathway is not involved in TNF-mediated cytotoxicity. Furthermore, results from cytotoxicity tests after exposure to staurosporine (PKC inhibitor) did not show any changes in the TNF-mediated cytotoxicity, confirming that a PKC-dependent pathway is not involved in this process. These data indicate that 1) TNF induces expression of c-fos, c-jun and jun-B oncogenes via a PKC-dependent pathway and 2) PKC-dependent expression of these three oncogenes by TNF may not be involved in TNF-mediated cytotoxicity in ME-180 cells.
문설희,김두열,이정민,박희원,이혜영,이용훈,이재성,정지원,김민주,최경백,오유경,김영봉,김수정,오승민 환경독성보건학회 2014 환경독성보건학회지 Vol.29 No.-
Objectives The sub-acute toxic effects following repetitive intramuscular injection of twocervical cancer vaccines newly developed against human papillomaviruse (HPV)16/58/18and HPV16 were investigated in female ICR (CrljOri: CD1) mice, and the no-observedadverse-effect-level (NOAEL) of the cervical cancer vaccines was estimated. Methods Female ICR mice (n=15 in each group) were exposed to a 1:1 mixture of two cervicalcancer vaccines by repetitive intramuscular injection (once a week, 5 times) for 5weeks. Mortality, body weight, organ weight, hematological/biochemical parameters, andhistopathological effects were examined at different concentrations (0, 1×108, 5×108, and2.5×109 copies/animal) of the cervical cancer vaccines. Results The cervical cancer vaccines did not show toxic responses for body weight, absolute/relative organ weight, hematological/biochemical parameters, or histopathologicalparameters. Conclusions Female ICR mice exposed to vaccines for cervical cancer did not show anytoxic response. We suggest that a NOAEL of the vaccine following repetitive intramuscularinjection for 5 weeks is >2.5×109 copies/animal.