당귀 추출물이 생쥐 유래 대식세포의 일산화질소 생산에 미치는 영향

조성기,하미혜,정영란,이성태,변명우 경산대학교 생명자원개발연구소 1999 생명자원과 산업 Vol.3 No.-

1. 당귀 물추출물 단독으로는 NO생성을 유도하지 못하였다. 2. 당귀 물추출물은 LPS 단독 또는 LPS와 IFN-γ에 의해 유도되는 NO생성을 증가시키지는 못하였다. 3. IFN-γ와 당귀 물추출물을 같이 처리하였을 경우 농도 의존적으로 NO생성을 유도하였다. 4. IFN-γ와 당귀 물추출물로 유도된 NO생성은 NOS 억제제인 ??에 의해 억제되었다. 5. 복강 대식 세포에서도 동일하게 IFN-γ와 당귀 물추출물의 NO생성에 대한 상승효과가 나타났다. In this study, the objective was to determene the effect of Angelica gigantis Radix-water extract on the production of nitric oxide(NO). Angelica gigantis Radix-water extract had no effect on NO synthesis by itself. However the stimulation of mouse macrophage cell line(RAW264.7) with Angelica gigantis Radix-water extract after the treatment of murine interferon-γ(mIFN-γ) resulted in increased NO synthesis. When Angelica gigantis Radix-water extract was used in combination with mIFN-γ, there was a marked co-operative induction of NO synthesis in a dose-dependent manner. The same results were obtained in the mouse peritoneal macrophages used. The optimal concentration of Angelica gigantis Radix-water extract on NO synthesis was shown 100㎍/mL with 100U/mL of mIFN-γ. NO synthesis was inhibited by ??-monomethyl-L-arginine. Angelica gigantis Radix-water extract was endotoxin free. Theses results suggest that Angelica gigantis Radix-water extract can induces NO synthesis of mouse macrophage cell line (RAW264.7) and peritoneal macrophages in combination with mIFN-γ

당귀 물추출물의 면역증강 효과

조성기,이성태,유영법,박혜란 경산대학교 생명자원개발연구소 1999 생명자원과 산업 Vol.3 No.-

천연물로부터 생체의 방어력을 증강시킬 수 있는 면역조절물질을 발굴하기 위한 목적의 일환으로, 한방에서 보혈에 관련하여 널리 사용되고 있는 당귀가 면역계에 미치는 영향을 검토하였다. 당귀추출물은 실험관 내에서 lipopoly-saccharides(LPS), phytohemagglutinin(PHA)와 같은 수준의 lymphcoyte 증식 효과를 보였으며, 그 효과는 LPS보다 오랫동안 지속되었다. LPS가 강력한 B cell mitogen이지만 생체내 독성이 심하여 투여가 어려운 반면, 당귀추출물에 의한 생체내 독성은 거의 없으므로 앞으로 생체내 투여 가능성이 있을 것으로 사료된다. Mouse에 투여하였을 때에도 당귀추출물은 SRBC에 대한 항체를 생성하는 lymphocytes의 수를 증가시켰으며, GVH 반응도 증가시켜 주었다. 따라서 당귀의 면역계에 대한 효과는 B cell의 증식과 그에 따른 항체 생성의 증가 뿐만아니라, T cell 매개 면역반응의 증가에 의한 것으로 생각되며, 앞으로 인체의 면역계에 미치는 효과 및 그 기작에 관한 많은 연구를 통하여 당귀가 면역증강제로 개발될 가능성이 있을 것으로 사료된다. The effects of Angelica gigas Nakai, which has been used as a blood-building decoction for recovery from weakness in the Chinese medicine, were examined for the purpose of screening a new nontoxic immunomodulator. The water extract of Angelica gigas Nakai showed a strong mitogenic effect on splenocytes in vitro to the same level of lipopolysaccharide(LPS) and phytohemagglutinin(PHA). Splenocytes stimulated with the extract in vitro, survived longer than that with lipopolysaccharide(LPS). LPS is a powerful B cell stimulant. However, it is now entirely restricted to only experimental purposes because of the highly toxic nature. Compared with this, the extract of Angelica gigas Nakai did not show any acute toxicity in mice injected intraperitoneally at a dosage of 1g/kg-body weight. It was tested in a hemolytic plaque assay whether in vivo treatment of the extract of Angelica gigas Nakai could influence the secretion of antibodies against sheep red blood cells(SRBC). It turned out that intraperitoneal(i.p.) injection of the extract of Angelica gigas Nakai for 4 days increased the number of antibody-secreting cells remarkably. Splenomegaly, due to graft versus host reaction, was also increased after 7 days i.p. treatment of the extract of Angelica gigas Nakai. These results indicated that the extract of Angelica gigas Nakai might be a useful immunomodulator, especially since it is a relatively nontoxic natural product.

동종 말초혈액 조혈모세포를 이용한 다양한 임상적용에 관한 단일병원 경험보고

채의수,손상균,성우진,서광운,박성원,김종광,정진태,이난영,서장수,이규보 경북대학교 병원 2002 경북대학교병원의학연구소논문집 Vol.6 No.1

배경:동종 말초혈액 조혈모세포 이식은 골수이식에 비해 많은 양의 조혈모세포 및 T―림프구 이식으로 인해 빠른 회복이 가능하며 강력한 이식편대종양반응이 유도될 수 있는 장점이 있어 이를 잘 응용한다면 악성 혈액질환에서 치료율을 높일 수 있을 것으로 사료된다.본 연구에서는 동종 말초혈액 조혈모세포 이식의 장점을 이용한 다양한 임상적용을 소개하고자 한다. 방법:경북대학교병원 조혈모세포 이식센터에서 동종 말초혈액 조혈모세포 이식을 시행한 증례 중에서 동종 골수이식수술에 비해 말초혈액 조혈모세포 이식이 유리할 것으로 생각디는 재발의 가능서이 높은 악성질환에서의 더욱 강력한 이식편대종양반응 유도를 위한 동종 말초혈액 조혈모세포를 이용한 예방적 공여자 림프구주입 등의 임상적용을 시도한 증례 및 결과를 분석하였다. 결과:17례의 재발의 가능성이 높은 고위험군의 악성 혈액질환을 대상으로 한 동종 말초혈액 조혈모세포 이식에서 90일 이내의 치료와 관련된 사망률은 23.5%이었고 중앙 추적기간 563일(범위 120∼926일)간의 무병생존율은 35.3%이었다.CSF로 가동화한 말초혈액 조혈모세포를 추가적으로 수혈받은 환자 7명 중 4명(57.1%)이 중앙 추적기간 538일(범위120∼926일)째에 완전관해 상태로 생존 중에 있다.그 외 말초혈액 조혈모세포를 아용한 미니 이식,동종 말초혈액 조혈모세포를 이용한 예방적 stepwise dose-increment 공여자 림프구주입술 등을 시행한 증례에서 장기 생존의 결과를 보여주고 있다. 결론:동종 말초혈액 조혈모세포 이식은 많은 양의 조혈모세포 및 T-림프구의함유로 인해 높은 생착률과 빠른 회복,강력한 이식편대종양반응 등이 유도되는 장점이 있으므로 기존의 골수이식술에 비해 보다 광범위한 임상적용이 가능하리라 사료된다. Background: It is apparent that more stem cells can be harvested by mobilization treatment with recombinant human G-CSF and/or GM-CSF from normal healthy donors in allogeneic peripheral biood stem celltransplantation(allo-PBSCT) compared to allogeneic bone marrow transplantation(allo-BMT).It is also known to be more effective in inducing the graft-vs-tumor affects than allogeneic BMT because of higher T cell content. Methods: A variety of clinical applications with allo-PBSCT was done for patients with hematoligical malignancies with a high risk of relapse in sigle transplantation center. We reported the preliminary results on trial of allo-PBSCT followed by planned prophyactic G-and/or GM-CSF primed donor lymphyocyte infusion additionally reserved at harvest in hematological malignancies with a high risk of relapse and also presented the successful trial of non-myeloablative transplantation for old aged AML paient in 4th complete remission and cases with 2nd transplantation with allo-PBSCs. Results: Seventeen patients with hematological malignancies with a high risk of relapse were enrolled in trial of allo-PBSCT followed by prophylactic donor lymphocyte infysion.All patients received allogeneic PBSCT from HLA- matched sibling donor.Aeven out of 17 patients recived additional PBSCs with a median number of CD3+ CELLS OF 5.0×10^7/kg(range,3.0 to 9.9×10^7/kg), between day 41 and day 120.Four surving patients(4/7) were free of disease when last assessed(median follow-up duration, 538 days), but were suffering from chronic GVHD(1 limited and 3 extensive). A 56 year old acute myeloid leukemia patient in the 4th complete remission was successfully treated with allo-PBSCT with non-myeloablative conditioning regimen.One of 2 patients who received second transplantation with allo-PBSCT has shown a long term disease free survival. Conclusion: A merit of allo-PBSCT would allow us to design a variety of clinical applications. Allo-PBSCT might be preferable in special clinical setting such as non-myeloablative transplantation, second transplantation,or the situation in need of the strong GVL effect. And also CSF-primed PBSCs can be used for the purpose of donor lymphocyte infusion.(korean J Hematol 2001;36:214~222)

1993년에 유행한 무균성 뇌막염 : 서울지역 소아를 대상으로 The study of pediatric patients in Seoul, with the emphasis on the isolation of causative agent

문형남,고태성,박영서,박윤아,홍창희 울산대학교 의과대학 1994 울산의대학술지 Vol.3 No.1

From May to July 1993, we observed an epidemic of aseptic meningitis. We performed clinical and virological studies on 174 children with aseptic meningitis who had been admitted to the Department of Pediatrics, Asan Medical Center, from May to July, 1993 The results were as follows; 1) This epidemic of aseptic meningitis was most prevalent in June 1993. The most of the patients were 3 to 6 years old and male to female ratio was 1.6 : 1. 2) The most patients suffered from fever, vomiting, headache, and abdominal pain was noticed in 36% of patients, characteristically. 3) In 7 cases among 10 randomly sampled cases, enterovirus was cultured. Among them, we performed serotyping in 3 cases and Echovirus 9 was isolated.

The Radioprotective Effects of Bu-Zhong-Yi-Qi-Tang as a Prescriptions of Traditional Chinese Medicine in Irradiated Mice

( Sung Mo Kim ),( Se Ra Kim ),( Heon Oh ),( Jung Ah Yang ),( Sung Kee Jo ),( Myung Woo Byun ),( Sung Tae Yee ) 한국수의병리학회 2000 학술대회 Vol.2000 No.-

We perfornlecl this stucly to determine the effect of BLI-Zhong-Yi-Qi-Tang, as a prescription of traditional Oriental medicine, and its major ingreclients 011 jejunal crypt s~u-vival, enclogenous spleen colony formation, and apoptosis in jejunal crypt cells of mice irracliatecl with high ancl low close of 7 -racliation. Bu-Zhong-Yi-Qi-Tang aclinii~istration before irradiation protected the jejunal crypts (p<0.0001), increased the formation of endogenous spleen colony (p<0.05) and reduced the frecluency of radiation-ind~~cecal poptosis (p<0.05). In the experiment on the effect of ingreclients of Bu-Zhong-Yi-Qi-Tang, the result indicated that the extract of Rensan (Panax ginseng), Danggui (Radix Angelicae sinensis), Shengma (Rhizoma Cimicifugae) ancl Chaihu (Raclix Bupleuri) might have a major radioprotective effect. Although the mechanisms of this inhihitory effect remain to he elucidated, these results inclicatecl that Bu-Zhong-Yi-Qi-Tang might be a useful radioprotector, especially since it is a relatively nontoxic natural product. Further studies are needed to characterize better the protective nature of Bu-Zhong-Yi-Qi-Tang extract ancl its ingreclients.

[P10-91] A Herbal Composition (HemoHIM) Protects the Sell­Renewal Tissues and Immune System against γ-Irradiation

Sung-Kee Jo,Hae-Ran Park,Uhee Jung,Sung-Ho Kim,Sung-Tae Yee 한국식품영양과학회 2006 한국식품영양과학회 학술대회발표집 Vol.2006 No.10

과산화수소의 산화적 스트레스로 유도된 Apoptosis에 대한 생약복합조성물(HemoHIM)의 방호효과 평가

신성해(Sung-Hae Shin),김도순(Do-Soon Kim),김미정(Mi-Jung Kim),김성호(Sung-Ho Kim),조성기(Sung-Kee Jo),변명우(Mung-Woo Byun),이성태(Sung-Tae Yee) 한국식품영양과학회 2006 한국식품영양과학회지 Vol.35 No.9

본 연구팀에서는 방사선으로부터 위장관과 면역조혈계를 방호하기 위하여 당귀, 천궁, 백작약으로 새로운 생약복합물 HIM-I을 개발하였고, HIM-I을 에탄올 침전하여 에탄올 분획(HIM-I-E)과 조다당 분획(HIM-I-P)을 얻은 후, HIM-I에 조다당 분획을 첨가하여 HemoHIM을 제조하여 실험하였으며, 과산화수소를 이용하여 산화적 스트레스를 유발한 후 HemoHIM의 apoptosis 억제 효과를 측정하였다. 과산화수소를 세포주에 처리한 결과 세포독성 증가, 세포막 파괴, subG1기 세포 증가, DNA 절단 현상 등이 관찰되었다. 이때 HIM-I, HIM-I-P, HemoHIM을 첨가하여 전처리 배양한 다음에 과산화수소로 apoptosis를 유도하였다. 그 결과 과산화수소에 의한 세포독성, 세포막 파괴, subG1기 세포, DNA 절단현상 등이 현저하게 감소하는 것으로 나타났다. 전반적으로 HemoHIM의 방호 효과는 HIM-I-P와 비슷하였으며 HIM-I보다 높은 것으로 나타났다. 이상의 결과로 HemoHIM은 면역기능 방호?회복 물질로서 뿐만 아니라 산화적 스트레스에 대한 항산화제로서 유용하게 활용될 수 있을 것으로 생각된다. In our previous study, a novel herb mixture (HIM-I) of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix was developed to protect the intestinal and immune systems and promote its recovery against radiation damage. A new herbal composition (HemoHIM) with the high immune modulating activity was developed from HIM-I. HIM-I was fractionated into ethanol fraction (HIM-I-E) and polysaccharide fraction (HIM-I-P). And HemoHIM was prepared by adding HIM-I-P to HIM-I. HemoHIM showed more effective than HIM-I in immune modulation as well as radioprotection. The present study is designed to investigate the protective effects of HIM-I, HIM-I-P, and HemoHIM on hydrogen peroxide (H₂O₂)-induced apoptosis of human promyelocytic leukemia (HL-60) cells. It was shown that H₂O₂ treatment reduced the viability of cells, and increased appearance of DNA ladders, hypodiploid (subG1) cells, and phosphatidylserine translocation level. Pretreatment of HemoHIM significantly reduced the cytotoxic effect induced by H₂O₂, associated with reducing the translocation of phosphatidylserine, hypodiploid cells and DNA ladders. HemoHIM appeared to be more protective than HIM-I against H₂O₂-induced apoptosis whereas, it exhibited similar activity to HIM-I-P. These results indicated that HemoHIM might be an useful agent for protection against oxidative stress (H₂O₂)-induced apoptosis as well as immune modulation, especially since it is a relatively nontoxic natural product.

보중익기탕(補中益氣湯)의 B세포 분화 유도 효과

신성해(Sung-Hae Shin),채수연(Su-Yeon Chae),하미혜(Mee-Hye Ha),조성기(Sung-Kee Jo),김성호(Sung-Ho Kim),변명우(Myung-Woo Byun),이성태(Sung-Tae Yee) 한국식품영양과학회 2004 한국식품영양과학회지 Vol.33 No.2

최근에 방사선 조사에 대해 방호효과를 가지는 것으로 알려진 보중익기탕의 골수세포 분화 유도 효과에 대해 관찰하였다. 시험관에서 골수세포를 배양했을 때, 배양시간(5일, 10일)에 따라 대조군의 세포 수는 현저히 감소하였고, 보중익기탕의 total 분획을 첨가하였을 때도 비슷한 결과를 얻었다. 그러나 polysaccaride 분획을 첨가하였을 때는 감소하는 세포수가 일정한 수준에서 유지되며 더 이상 감소하지 않았다. 그리고 이들 세포가 어떤 종류의 세포인지를 유세포분석기로 분석한 결과, Pre-B세포의 특징적인 세포 표면 단백질인 CD19와 CD40을 동시에 발현한 세포인 것이 확인되었다. 또한, 이들 세포는 분화과정이 끝난 B세포가 분비하는 IgM 뿐만 아니라 IgG1, G2a, G3를 분비하였다. 이상의 결과 보중익기탕의 polysaccaride 분획에 골수세포가 B세포로 분화 증식하는 것을 유도하는 성분이 포함되어 있어 방사선 조사로 상해를 입은 조혈계에 대한 방호 효과를 나타내는 것으로 생각된다. This study was designed to evaluate the effect of Bu-Zhong-Yi-Qi-Tang extracts, a prescription of traditional oriental medicine, on development of the B cells. In the bone marrow cell cultures, progenitors viability, expressions of particular cell-surface proteins and production of immunoglobulins were investigated in the presence of Bu-Zhong-Yi-Qi-Tang extracts. The administration of Bu-Zhong-Yi-Qi-Tang polysaccharide fraction increased the viable cell numbers of the precursor B cells, and elevated expression levels of CD19/CD40 specific for pre-B cells after 10 days culture were demonstrated by flow cytometry analysis. The production of immunoglobulin M in the presence of polysaccharide fraction increased progressively in the culture supernatant, and preferentially induced class switching to IgG1, IgG2a and IgG3. These results indicated that Bu-Zhong-Yi-Qi-Tang strongly correlated with the development of precursor B cells in the bone marrow cell culture. Therefore the polysaccharide fraction of Bu-Zhong-Yi-Qi-Tang might be a useful radioprotector, especially since it is a relatively non-toxic natural product. Further studies are needed to better characterize the protective nature of Bu-Zhong-Yi-Qi-Tang extract.

가토 신피질 절편에서 Uric Acid 이동

이성태(Yee, Sung-Tae),임채준(Lim, Chae-Joon),우재석(Woo, Jae-Suk),김용근(Kim, Yong-Keun) 대한생리학회 1987 대한생리학회지 Vol.21 No.2

Uric acid transport across the basolateral membrane of renal proximal tubules was studied in rabbit kidney cortical slices. Uric acid uptake was greater under O₂ atmosphere compared to under N₂ atmosphere, and was increased with Na²⁺} concentration in incubation medium. Uric acid inhibited PAH uptake but not TEA uptake and did trans-stimulated PAH efflux. PAH also inhibited uric acid uptake. Uric acid uptake was inhibited by harmaline, ouabin, SITS, DIDS and pyrazinoic acid. The inhibition of PAH uptake by these inhibitors also was reasonably comparable to that of uric acid uptake. These results suggest that uric acid was transported across the basolateral membrane of renal tubule by a carrier-mediated process which was by a common transport system with PAH in rabbit.

방사선에 대한 생약복합조성물(HemoHIM)의 재생조직 및 면역계 방호ㆍ회복촉진 효과

조성기(Sung-Kee Jo),박혜란(Hae-Ran Park),정우희(Uhee Jung),오헌(Heon Oh),김성호(Sung-Ho Kim),이성태(Sung-Tae Yee) 한국식품영양과학회 2005 한국식품영양과학회지 Vol.34 No.6

본 연구팀에서는 방사선으로부터 위장관과 면역조혈계를 보호하기 위하여 당귀, 천궁, 백작약으로부터 새로운 생약복합물 HIM-I을 개발한 바 있다. 본 연구에서는 방사선 방호뿐 아니라 다양한 생체질환의 예방에 있어 면역조혈기능이 중추적인 역할을 한다는 관점에서, HIM-I로부터 면역조혈 기능을 더욱 증진시킨 생약복합조성물 HemoHIM을 제조하여 그 효능을 검증하였다. HIM-I를 에탄올 침지하여 에탄올 분획(HIM-I-E)과 조다당 분획(HIM-I-P)을 얻은 후, HIM-I에 조다당 분획을 첨가하여 HemoHIM을 제조하였다. 이렇게 얻은 HemoHIM, HIM-I 및 각 분획에 대하여 재생조직 및 면역계 방호와 회복촉진 효과를 비교 검증하였다. HemoHIM과 HIM-I는 시험관내에서 방사선에 의한 DNA 손상을 유의적으로 억제하고 수산화 라디칼을 소거하는 효과가 있음이 관찰되었으며, HemoHIM과 HIM-I는 거의 비슷한 활성을 나타내었다. 시험관내 면역세포 활성화와 골수세포 성장촉진 실험에서는 HemoHIM이 HIM-I에 비하여 높은 활성을 보였으며, 이는 HIM-I에 비해 높은 조다당 함량에 기인한 것으로 보인다. 감마선 조사 마우스를 이용한 생체 보호효과를 살펴본 결과, HemoHIM은 HIM-I와 비슷한 정도의 소장움 생존율 증가효과를 보였으나, 내재성 비장 조혈세포집락 형성시험에서는 HemoHIM은 HIM-I보다 높은 효과를 나타내었다. 또한 방사선조사 마우스에서 HemoHIM의 투여는 방사선 조사후 급격히 감소된 말초 혈액내 백혈구 및 림프구수의 회복을 촉진시키고, 생존율을 증대시키는 효과가 관찰되었다. 이상의 결과들은 생약복합물 HIM-I에 조다당 분획을 첨가하여 개발한 새로운 생약복합조성물 HemoHIM이 방사선에 의해 유발된 위장관 및 면역계 조직의 손상을 감소시켜 생존을 증가시키는 효과가 있음을 제시하였다. 특히 HemoHIM은 HIM-I와 비교하여 재생조직의 산화적 손상억제 효과는 비슷하게 유지되면서도 면역조혈세포 방호 및 회복촉진 효과가 높은 것으로 관찰되어 방사선 방호제로서 뿐만 아니라 면역조혈기능 증진제로서 유용하게 활용될 수 있을 것으로 사료된다. In our previous study, a novel herb mixture (HIM-I) of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix was developed to protect the intestinal and immune systems and promote its recovery against radiation damage. In this study, a new herbal preparation (HemoHIM) with the high immune modulating activity was developed from HIM-I. HIM-I was fractionated into ethanol fraction (HIM-I-E) and polysaccharide fraction (HIM-I-P). And HemoHIM was prepared by adding HIM-I-P to HIM-I. The protective activities against γ-irradiation were compared among HemoHIM, HIM-I and the fractions. HemoHIM and HIM-I significantly decreased the radiation-induced DNA damage in vitro, and scavenged hydroxyl radicals in a dose-dependent manner. HemoHIM showed similar activity to HIM-I. In vitro proliferation assay with mouse lymphocytes and bone marrow cells showed that HIM-I-P was remarkably higher than HIM-I and HIM-I-E in cell proliferating activity. HemoHIM showed higher activity than HIM-I and this might be associated with the higher polysaccharide content. The in vivo protective effects of HemoHIM and HIM-I were investigated in γ-irradiated mice. HemoHIM increased the surviving intestinal crypts to a similar extent compared with HIM-I. In contrast, HemoHIM appeared to be more effective than HIM-I in endogenous spleen colony formation assay. The recovery of white blood cells and lymphocytes in irradiated mice were significantly enhanced by the administration of HemoHIM. Also HemoHIM administration prolonged the survival of irradiated mice. These results showed that the novel herbal preparation, HemoHIM, effectively protected the self-renewal tissues and immune system, and promoted the survival of irradiated mice. Moreover, in comparison with HIM-I, HemoHIM maintained similar activity in the reduction of oxidative damage of self- renewal tissue but exhibited the higher activity in protection and proliferation of immune and hematopoietic cells. These results suggested that HemoHIM might be more effective than HIM-I in immune modulation as well as radioprotection.