자가면역질환(Autoimmune Disease)의 실체와 치료

韓馨美 약사공론 1993 대한약사회지 Vol.1993 No.2

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.

제 36차 EUROTOX ( 유럽독성학회 ) 에 다녀 와서

한형미 한국독성학회 1998 한국독성학회보 Vol.12 No.1

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.

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.

동맥경화질환 동물모델을 이용한 약효검색 연구

김태균,한형미,박민수,강석연,정기경,강주혜,최돈하,김승희,류항묵 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

동맥경화증은 미국, 유럽뿐만 아니라 우리나라에서도 죽요 사망원인으로 대두되고 있으며 심혈관계 질환의 대툰분 즉 뇌혈관 질환, 판상동맥 질환,고혈압 및 말초혈관의 홉착 둥이 동맥경화증의 진챙에 의해 발병한다. 본 연구에서는 토끼와 CETP 형질전환 동물모질을 이용하여 느릅나무 수괴의 에탄을 추출물(0.5%), 산마늘의 탄을 추출물(0.5%』과 curcumin(0.1%, 0.5%)의 콜레스테를 저하 및 항동맥경화 효과를 관찰하였다. 토끼 실험결과,느릅나무 수펴 투여군은 혈중 촌 콜레스테롤과 LDL-콜궤스테롤의 농도가 감소 되었으며 간과 심장 조직에서 콜궤스데롤과 TG지질의 함량이 감소히는 것으로 나타났다. 산마늘 투여군에서 혈중 총 콜레스데를 농도는 20.8%(p(0.05) 감소하였교,LDL-콜레스데를 농도의 21-8% (p(0.01) 감소하였다. 간과 심장 조직의 충 걸궤스데를 함량은 각각 45.1% (p(0.05),66.4% (p(0.01) 감소하였다. 0.5% curcumin 투여군은 혈중 총 콜궤스데를 농도, LBL-콜레스데를 농도, 과살화지 질 농도가 유의하게 감소되었고 간파 심장 조직의 TG 함량이 감소되었다. 식험동물의 대동맥을 oil red 0로 염색한 결과, 산마늘과 curcumin 투여군의 대동맥에서 지방반과 아테로마의 형성이 감소되었음이 관찰되었다. CETP 형질 전환 마우스 실험결과,산마늘은 혈중 총 콜레스테를 농도를 9.4% 낮추며 심장의 TG 함량을 낮추는 것으로 나타났다. 본 연구결과에서 느릅나무 수피, 산마늘과 curcumin은 혈액과 조직에서 동맥경화의 병인인 지질과 과산화지질의 농도를 낮추는 갓으로 나타났으며, 산마늘과 curcumin은 동맥의 지질침착을 감소시켰다. 이러한 작용을 나타칙는 약리활성 물질의 꽉인과 기전을 밝히기 위한 좀더 싱도있는 연구가 수쳉되어야 할 것이다. Atheroscler(osis is emerging as one of the majrlr causes of death in Korea as well as Western societies. Most of cardiouascular diseases such as cerebi·ovascular diseases, coronary artery dieeases, hypertension and gangrene result from progress of atherosclerosis. In the present studf,hypocholesteremic and ant:j-atherogenic effect of curcumin(0.1%, 0.5% ) ffmus cravitridna (ethanot eE-tract, 0.5% ) and fffiurt vicforiaff (ethanol extract, 0.5% ) was investigated using conventional rabbitmodel snf cholesteryl ester transfer protein(CETP ) transgenic mouse model. In the experimeot usingthe rabbit model, treatment, with tl daoidiana extract decreased total serum cholesterol and LDL-choles-terol levels as well as tissue chotesterol and triglyceride levels in the heart and the liver. In the rt.oicforiafig-treated group, serum total cholesterol was decreased 13y 20.8% (P <0.05) and LDL-chotesterol by 21.8% (P <0.01). Totat cholesterol contents in the liver and the heart were also decreased by 45.19(P<0.05)』 66.4% (P<0.01), respectively. Treatment with 0.5:4 curcumin significantly decreased the level of total cholesterol,1,DL-cholesterol and malondialdehrdes in the serum and the level of trigtyc☞rides in the liver and the heart. Oil red 0 staining of the aorta isolated from the experimental animals showed that treatment wit'h rt. oiooridfia extract or curcumin decreased fatty streaks aBd atheroma for-mation -ff the aorta. In thr experiment employing CETP transgenic mouse model, f. ufcforiafis eBtractdecreased the level of total eholesterol by 9.4% and the tissue triglyceride levels in the heart. Theseresults demonstrated that V daoidiana and 4. oicforiafis extracts and curcumin decreased the level ofblood serum cholesterol, tissue cholesterol and triglyceride levels, and f. vidoriafis extracts apdcurcumin decreased the cholesteiol accumulation on th,e aorta. The precise mechanism ofhypocholesteremic effect of these plant extracts and curcumin remains to be elucidated.

Pesticide가 면역계에 미치는 영향에 관한 연구(Ⅱ) : Effects of methidathion and pyridaphenthion on the humoral immunity in mice

김형수,한형미,정혜주,김필선,박재현,김진호,정승태,윤여표,김주일 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

유기인계 농약인 methidathion과 p'fridaphenthion이 면역계에 미채는 영향을 살펴보고자 BALB/C 마우스에 저용량(0.5mg/kg)및 고용량 (5.0mg/kg)의 methidation 또는 저용량(4.6mg/kg) 및 고용량(46mg/kg)pyridaphenthion을 14일간 경구투여후 체중변화및 훙선등 면역관련장기의 무게 변화를 측정하고 면역적혈구에 대한 PFC측정 및 HEL에 대한 IgG항체가를 ELISA를 이용하여 측정하엿으며 조직병리학적 관찰을 행하엿다. 체중의 경우 methidathion 및 pyridaphenthion 고용량투여군에서 유의성있는 짬소를 나타냈으며, 면역관련장기의 경우 비장을 제외한 훙선, 신장, 간장의 상대적 무게를 유의성있게 증가도는 감소기켰으나 일관성있는 변화을 관찰할 수 없었더, PGG의 경우 methidathion및pyridaphenthion모든 투여군에서 비장당 및 비장 세ㅠㅗ당 프랄크형성능을 유의성있게 저하(p<0.001)시켰고, IgG항체가 측정의 경우에는 rnethidathioa 및 pyridapheuthion고용량군에서안 유의적 저하(p<0.05)를 관찰할 수 있었다. 조직병리학적관찰에서는 methidathion 및 pyridaphenthion 고용략틀 여군의 간과 신장조직에서 공히 세포변성이 나타났으며, 신장에서의 충출혈이 관찰되었다. 또한 홍선 및 비장조직에싻는 현저한 임파구 감소와 비장에서 거대핵세포가 관찰되었다. 특히 methidathion 투여군에서는 신장조직에서의 보운 만낭 위축 및 흥선에서의 충출혈 소견이 관찰되었다. 따라서 methidathion 및 pyridaphenthion은 체액성 면역능을 저하시키는 것으로 사료된다. The effects ()』 methidathion and pyridaphenthion on immune system were studied in BALB/C mice by assessment of body and organ weight, immune function tests like plaque forming eells(fFC) assar and engyme-linked immunesorbent assay (ELISA ) anfl histepathological eraminations.Methidathion (0.5,5.Omg/kg) and pyridaphenthioB (4.5,46mg/kg) wel·e given to mice orally for 14 daysand the each parameter waf evaluated on the day 15. Mice were immunized with sheep red blood cells(SRBC) on the day 11 for fFC assay and heE egg Iysozyme (HEL) was injected peritoneally on the day0 aBd 8 for ELTSA. Body we;ights were decreased signi(icantly (p<0.05) both in methidathion (5.Omg/kg) and pyridaphenthien (46mg/kg) treated grovps, but there was no consistency in changes of ralattveorgan weight, even though t;he weights of thymus, kidney and liver were increased or decreased signifi-cantly after treatment. The antibody response to SRBC was inhibited (p <0.001) in all pesticide-treatedgroups, whereas serum fge titer to HEL was only reduced (p<0.05) in methidathion (5.Omg/kg) andryridaphenthioa (46mg/kg) treated groups. Some abnormal changes in spleen, thymus, liver and kidneytissues w?fa: observed in methidathion(5.Omg/kg) and pyridaphenthion(46mg/kg) treated groups byhistopathological examiaations. These results suggest that methidathion and pyridaphenthion may sup-press the humoral immunity in mice.

객체지향방법론을 이용한 프로세스모델링에 대한 연구 - 복수 모형의 인지적 통합과정을 중심으로 -

김진우,한형미 한국경영정보학회 1996 Asia Pacific Journal of Information Systems Vol.6 No.2

수은이 시험관내 사람 다형핵백혈구의 기능에 미치는 영향

김효정,한형미,김순한,김옥연,선우연,윤은이 한국응용약물학회 1993 Biomolecules & Therapeutics(구 응용약물학회지) Vol.1 No.2

In the present study, the effect of HgCl₂ on the function of human peripheral polymorphonuclear leukocytes(PMNs) was examined. PMNs were isolated from human peripheral blood with density centrifugation in Ficoll-Paque. The cells were then incubated with 0.5∼5 μM HgCl₂ and glass adherence, chemotactic activity and erythrocyte-antibody rosette forming activity were measured. HgCl₂ decreased the function of PMNs in all three aspects tested. HgCl₂ significantly diminished glass adherence(0.5 μM: 92±12% (percentage of control, mean±S.D.); 1μM: 46±11%, P<0.01; 3 μM: 35±7%, P<0.01; 5 μM: 49±10%, P<0.01). Similarly, significant differences were observed in chemotactic activity after HgCl₂ treatment compared with control (control: 0.95±0.14 mm; 0.5μM: 0.91±0.11 mm; 1μM: 0.77±0.16 mm, P<0.05; 3μM: 0.61±0.06 mm, P<0.01; 5μM: 0.15±0.03 mm, P<0.01). Also, HgCl₂ decreased the percentage of rosette-forming PMNs, indicating diminished phagocytic activity of PMNs upon HgCl₂ exposure compared with control (control: 58±4%; 1 μM: 53±4%, P<0.05; 3 μM: 49±3%, P<0.01; 5 μM: 46±3%, P<0.01). Cell viability was not altered after HgCl₂ treatment (83±5% viability in control PMNs versus 81±8% viability in 5 μM HgCl₂-treated PMNs), suggesting that the impaired PMN function after HgCl₂ treatment was not due to nonspecific cytotoxicity induced by HgCl₂. HgCl₂-induced decrease in the function of PMNs may have some implications in depressed host susceptibilityupon bacterial challenge after mercury exposure.

노인성치매에 대한 생화학적 연구(Ⅱ) : DHA와 DHEA가 흰쥐에서 Ibotenic acid로 유발된 능동적조건회피반응감소에 미치는 영향에 관한 연구 Effects of DHA and DHEA on active avoidance impaired rats induced by ibotenic acid

강석연,한형미,정기경,김태균,안향숙,허인회,김승희 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

Alzheimer's disease(AD) is ass☞ciated wit31 feature of extracellutar deposition of firoos protein aggregation in the form of amyloid plaque and a loss of choliBergic neurons. This study'as designed to evaluate the effects of docosahexaenoir acid(DHA ) and dehydroepiandrosteroneDHEA) in animal models of dementia which wa:T induced by neurotoxin(iboteni acid ) and of alcohot(16) ethanol). Ibotenic acid was injected into the nucleus basalis meynert region of the rat brain byfreotarically. The oral doses of DHA (675mg/kg) and DHEA (130rng/kg) were given respectively dur-lg 24 days daily, and ibotenic acid was injected at 33th day and of alcohol was given during 48 weeks.he effects of DHA and OHEA were tested the active avoidance and activity of acetylcholinesterasetchs), AChB distrib'ution, amyloid protein distribution, synaptophysin distribution and lipidfroxidatfDn in the brfin. There were Bo differences in active avoidance, amyloid distribution,rnaptofsj,sin dist,ibution and lipid pe,oxidation by DHA, DHEA in the rat b.sin. The rats we.e3ministered DHEA only showed decrease body weight significantly. Alcohol had no e(fect on activeroidance. These findinB proposed that DHA and DHEA Irvels may not be related to the memory im-tirment induced by ibotenic acid.