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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.
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.
수종 생약재의 간염 B형 바이러스 증식 억제 활성 검색
김태균,한형미,강석연,정기경,김승희,Kim, Tae-Gyun,Han, Hyung-Mee,Kang, Seog-Youn,Jung, Ki-Kyung,Kim, Seung-Hee 한국생약학회 1999 생약학회지 Vol.30 No.3
This study was undertaken to test for anti-hepatitis B virus (HBV) activity of the aqueous extracts prepared from 9 medicinal plants of Korea (Cornus officinalis, Caesalpinia sappan, Rubus coreanus, Lycium chinense, Artemisia capillaris, Isatis tinctoria, Phyllanthus urinaria, Lysimachia christinae, Lonicera japonica). Aqueous extracts were tested for cytotoxicity and assayed for inhibition of HBV replication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium f HepG2 2.2.15 cells. The extract from Rubus coreanus, Artemisia capillaris, Phyllanthus urinaria decreased the levels of extracellular HBV virion DNA at concentrations ranging from 128 to $256\;{\mu}g/ml$ and inhibited the production fo HBsAg dose-dependently without showing cytotoxicity. Our findings suggest that these three hebal medicinal plants may have potential to develop as specific anti-HBV drugs in the future.
기니픽과 마우스에서 CFC-101 ( 녹농균 백신 ) 의 항원성시험
선우연(Woo Yearn Sun),한형미(Hyung Mee Han),김현수(Hyun Su Kim),백남진(Nam Jin Baek),김달현(Dal Hyun Kim),이동억(Dong Eok Lee),정승태(Seung Tae Chung),김필선(Pil Sun Kim) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.4
As a part of the safety evaluation of Pseudomonas vaccine(CFC-101), antigenicity tests were carried out in guinea pigs and mice. In active systemic anaphylaxis(ASA) test, guinea pigs showed no sign or only moderate sign(1/5) when sensitized and challenged with up to 200 ㎍/㎏. In homologous passive cutaneous anaphylaxis(PCA) test using guinea pigs, inoculation of CFC-101 alone did not produce CFC-101-specific antibody. When inoculated with 200 ㎍/㎏ plus adjuvant, challenge of 200 ㎍/㎏ produced PCA titer of 32(5/5) but challenge of 20 ㎍/㎏ did not produce CFC-101-specific antibody. In heterologous PCA test using mice, CFC-101-specific antibody was not detected when sensitized with CFC-101 alone. Some animals(3/12) showed positive PCA response when inoculated with 200 ㎍/㎏ plus alum. In passive hemagglutination (PHA) test, although no antibody was detected at 20 ㎍/㎏, inoculation of 200 ㎍/㎏ alone or with alum produced positive response in all animals. This result has already been predicted because CFC-101 is a vaccine developed for the purpose of immunization. From the above results, it can be concluded that there is no adverse antigenic potential up to 10 times clinical dose of 200 ㎍/㎏.
Methamphetamine 이 면역장기 및 항체생성능에 미치는 영향
선우연(Woo Yearn Sun),한형미(Hyung Mee Han),윤은이(Eun Yi Yoon),신전수(Jeon Soo Shin),박현애(Hyeon Ae Park),김미영(Mi Young Kim) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.1
BALB/c mice were intraperitoneally injected with methamphetamine (5 mg/kg) to observe the effect of methamphetamine on the immune system. Body weights were decreased in both acutely treated group (twice for 2 weeks with 7 days interval) and subchronically treated group (daily injection for 14 days). The relative spleen weights and the numbers of splenocytes were unexpectedly increased (p<0.05) in acutely treated group, but subchronically treated group showed the trend of decrease without significance. But there was no significant effect on antibody formation to hen egg lysozyme which was immunized during the treatment of methamphetamine and on plaque forming cell number. The relative thymus weights of both groups were significantly decreased by the treatment of methamphetamine (acutely treated group, p<0.05; subchronically treated group, p<0.01). These results suggest that the effect of methamphetamine on the immune system may be caused by thymic dysfunction.
기니픽과 마우스에서 신규 퀴놀론 항균제 DW-116 의 항원성 시험
권현진(Hyun Jin Kwon),한형미(Hyung Mee Han),김필선(Pil Sun Kim),이흠숙(Heum Sook Lee),정용호(Yong Ho Chung),윤성준(Sung June Yoon),이문선(Moon Sun Lee),이덕근(Dug Keun Lee) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.2
Antigenic potential of DW-116, a newly synthesized fluoroquinolone, was examined by conducting active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. In ASA test, mild to moderate signs of anaphylactic responses were observed in the groups sensitized with low (2 mg/body) and high (10 mg/body) doses of DW-116 alone and the group sensitized with DW-116 plus adjuvant. Some moderate to severe anaphylactic reactions were observed in the group sensitized with a DW-116-bovine serum albumin (BSA) conjugate plus adjuvant when challenged with a DW116-guinea pig serum albumin (GSA) conjugate. However these reactions were considered to be a cross-reaction between BSA and GSA since similar reactions were induced when challenged by GSA alone. In heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In PHA test, positive responses were observed in the groups sensitized with low and high doses of DW-116 alone and the group sensitized with DW-116 plus adjuvant. However, these responses were not considered to be drug-specific because some positive responses were also seen in the negative control group. From these results, it was concluded that DW-116 is not likely to have specific antigenic potential in clinical use.
Methamphetamine 이 B16 악성 흑색종 세포 전이에 미치는 영향
선우연(Woo Yearn Sun),한형미(Hyung Mee Han),신전수(Jeon Soo Shin),박현애(Hyeon Ae Park),정승태(Seung Tae Chung),김필선(Pil Sun Kim),손경희(Kyung Hee Sohn) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.4
The effect of methamphetamine on the pulmonary metastasis was investigated in C57BL/6 mice injected with B16 melanoma cells. B16 melanoma cells (2x10^5 cells) were injected intravenously into 5∼7 weeks old C57BL/6 mice. Mice were then treated intraperitoneally with methamphetamine either acutely (two times with one week interval) or subchronically (daily for 14 days). Degree of pulmonary metastasis was investigated and specific immunologic parameters such as natural killer cell cytotoxicity(NKCC), antibody-dependent cellular cytotoxicity(ADCC) and blastogenic responses of splenocytes were examined. Mice which had been subchronically treated with methamphetamine showed significant decreases in the number of pulmonary metastasis of B16 melanoma cells, NKCC and ADCC without a significant change in blastogenic responses. In the acutely-treated group, slight trends of decrease in the numbers of pulmonary metastasis, NKCC and ADCC were observed without statistical significances whereas there was a significant increase in blastogenic responses. The mechanism underlying the decrease in the degree of metastasis despite diminished NKCC and ADCC after methamphetamine treatment and the relationship between the degree of pulmonary metastasis and duration of methamphetamine treatment remain to be investigated.
동맥경화유발 토끼와 형질전환 마우스에서 산마늘 추출물의 항동맥경화 효과
김태균,김승희,강석연,정기경,최돈하,박용복,류종훈,한형미,Kim, Tae-Gyun,Kim, Seung-Hee,Kang, Soeg-Youn,Jung, Ki-Kyung,Choi, Don-Ha,Park, Yong-Bok,Ryu, Jong-Hoon,Han, Hyung-Mee 한국생약학회 2000 생약학회지 Vol.31 No.2
Atherosclerosis is emerging as one of the major causes of death in Korea as well as Western societies. In the present study; hypocholesterolemic and antiatherogenic effects of the ethanol extract of Allium victorialis Makino was investigated using the conventional rabbit and the cholesteryl ester transfer protein (CETP)-transgenic mouse model. Hypercholesterolemia was induced by feeding high cholesterol diet to the animals for 30 days and they were then fed with high cholesterol diet containing 0.5% of the A. victorialis extract for additional 30 (or 40) days. In the experiment using rabbits, treatment with the A. victorialis extract significantly decreased plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride levels and lipid peroxidation compared to those in the control group. Total cholesterol contents in the liver and the heart were also significantly decreased. Lipid staining of the aorta isolated from the rabbits showed that treatment with the A. victorialis extract decreased formation of atheromatous plaques on the intima of the aorta. In the experiment employing CETP transgenic mouse model, treatment with the A. victorialis extract decreased the levels of plasma total cholesterol and the tissue triglyceride levels in the heart. These results demonstrated that the ethanol extract of A. victorialis lowered serum cholesterol levels, tissue lipid contents and accumulation of cholesterol in the artery.
정향 , 마황 , 계피의 간염 B 형 바이러스 증식 억제 효과
강석연(Seog Youn Kang),김태균(Tae Gyun Kim),박민수(Min Su Park),한형미(Hyung Mee Han),정기경(Ki Kyung Jung),강주혜(Ju Hye Kang),문애리(A Ree Moon),김승희(Seung Hee Kim) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.2
This study was undertaken to test for anti-Hepatitis B virus (HBV) activity of the aqueous extracts prepared from Eugenic caryophyllate, Ephedra sinica, Cinnamomum cassia. Aqueous extracts were assayed for the inhibition of HBV replication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells. All extracts decreased the levels of extracellular HBV virion DNA at concentrations ranging from 128 to 256 ㎍/㎖ and inhibited the production of HBsAg dose-dependently. Our findings suggest that these three hebal medicinal plants may have potential to develop as specific anti-HBV drugs in the future.