• Korean Journal of Veterinary Research
• /
• v.41 no.2
• /
• pp.211-218
• /
• 2001

The $M_r$ 63,000 glycoprotein (GP63) and lipophosphoglycan (LPG) of Leishmania donovani were evaluated as vaccine candidates against visceral leishmaniasis. Mice were immunized with liposomeencapsulated GP63 and/or LPG that were purified from the soluble extract of L. donovani promastigotes, and were challenged with virulent amastigotes. Mice immunized with GP63/LPG in liposomes plus BCG resulted in a 27.4% reduction of amastigotes in the liver compared to the control group (liposomes plus BCG), and mice immunized with liposome-GP63 plus BCG failed to induce a protective immune response against the challenge infection. Immunization of mice with GP63 fused to the Schistosoma japonicum glutathione S-transferase (GP63-GST) plus BCG also failed to elicit protective immunity. To analyze the cause of failure to induce protection, cytokine release from the spleen cells of immunized mice and Leishmania-specific serum antibodies were analyzed. Spleen cells from mice immunized with GP63-GST plus BCG that were exposed to soluble extract of L. donovani in vitro produced 10-fold greater quantities of IFN-gamma and 3-fold greater quantities of IL-5 than cells from mice receiving BCG only or saline. Western blot analysis revealed that sera from these mice had Leishmania-specific antibodies recognizing 1 to 3 antigens of L. donovani with M. W. of 60-65 kDa. Although immunization of mice with GP63-GST induced a strong Th1 response, this study indicated that GP63-GST simultaneously elicited the Th2 response of the CD4+ T-cell, which was known to abrogate the protective immune response conferred by the Th1 effector function.

• Korean Journal of Food Science and Technology
• /
• v.33 no.6
• /
• pp.656-663
• /
• 2001

The most representative nitrosamine derived from nicotine, nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), has been reported to cause lung cancer in A/J mice. It has been also demonstrated that NNK-induced lung tumorigenesis involves $O^6-methylguanine(O^6MeG)$ formation, leading to $GC\;{\rightarrow}\;AT$ transitional mispairing during DNA replication. Our in vitro experiment, modified from the method of DBA assay, examined the ability of phyto-extract mixture to inhibit the metabolism of nicotine to nitrosamines. The production of nitromorpholine from morpholine was inhibited about 75% at the concentration of 20 mg/mL of phyto-extract mixture, which was lower than vitamine C and green tea powder. NNK, which is a pro-carcinogen in laboratory animals, is hydroxylated primarily in liver and lung by CYP 1A2, 2A6 and 3A4. A critical phase. of NNK activation is its change to an unstable metabolite methyl-diazohydroxide via CYP-mediated ${\alpha}-hydroxylation$; and then it provides a methyl group to the DNA to form DNA adducts which can easily induce mutations. $Aroclor^R$ 1254 was used to induce CYPs in the liver of a Sprague-Dawley rat. The ability of various test samples to inhibit CYPs that participate in NNK activation was evaluated, following the removal of the liver from the rat. Microsomal CYPlA2 catalyzing the conversion of NNK into strong carcinogenic chemicals was inhibited more efficiently by phyto-extract mixture than green tea powder. These results indicate that phyto-extract mixture can be used to reduce $O^6MeG$ DNA adducts for chemoprevention.

• Korean Journal of Food Science and Technology
• /
• v.30 no.3
• /
• pp.702-708
• /
• 1998

The effects of mushrooms such as Lentinus edodes and Pleurotus ostreatus on anti-cancer activity through in vivo and in vitro experiments were powders of protein-bound polysaccharides in mushrooms were solubilized in 0, 5, 25 mg/kg saline, respectively and were used in vitro experiments. The in vivo experiments were carried out as followed: i) anti-cancer activities on Leukemia $(L_{1210})$, Hepatlicus cancer $(H_{22})$ and Sarcoma180/(S180), and ii) the effect on immune system through changes in intestine weight and the number of hemolytic plague forming cells. Protein-bound polysaccharides of all showed anti-cancer activity on $L_{1210}$ and fruit body of Lentinus edodes 25 mg/kg treatment group showed the highest inhibition rate (86%). Pleurotus ostreatus mycelial in medium of cultivate 25 mg/kg treatment. Fruid body of Lentinus edodes 25 mg/kg treatment group showed the highest inhibition rate (86% and 71%, respectively) on $H_{22}$ among them. The inhibition rates of fruit body and mycelial of Lentinus edodes 25 mg/kg treatment groups on S180 were 33.9% and 30.9%, respectively. Each samples of 50, 100, 200, $400\;{\mu}g/{\mu}L$ on in vitro cell toxicity test did not show significantly different cell death rates at P<0.05. In immune test, weights of liver and spleen were increased according to increase in conc. but were not significantly different at P<0.05. The weights of thymus were heavy in fruit body and mycelial of Lentinus edodes treatment group but were not significantly different at P<0.05. Hemolytic plague forming cells with antibody formation capability were significantly high in fruit body and mycelial of Lentinus edodes treatment samples.

• Journal of Korean Medicine Rehabilitation
• /
• v.25 no.1
• /
• pp.27-44
• /
• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• Archives of Pharmacal Research
• /
• v.20 no.3
• /
• pp.253-258
• /
• 1997

Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

• Journal of Acupuncture Research
• /
• v.25 no.4
• /
• pp.81-94
• /
• 2008

Rheumatoid arthritis(RA) is a general, chronic, inflammatory and auto-immune disease and it can lead to joint edema, pain, stiffness which are caused by an inflammation in synovium covering our joints. Ulmus davidiana Planchon is a traditional herb used for the treatment on various inflammations, gastrointestinal trouble, ENT(ear, nose, and throat) disease, edema, cancer etc. and it works effectively on arthritis as well. In these study to search for the treatment efficacy of Ulmus davidiana Planchon in RA, I measure manifestation of cytokine gene in synoviocyte treated with Ulmus davidiana Planchon herbal acupuncture and in EL-4 cell, manifestation of cytokine gene cell related to T-cell. And after Ulmus davidiana Planchon herbal acupuncture treatment in Collagen induced arthritis(CIA) which has been known by a general model of RA, DBA mice, I observed foot thickness, general shape of synovium, early cytokine induce CIA and, generation and mutation of cytokine related to the control of T-cell specialization. It comes to conclusion as belows. 1. In synovium treated with Ulmus davidiana Planchon herbal acupuncture, there was the decrease in MIF mRNA does-dependently. Incase of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in the damage in synovium and generation of the MIF which is related to induction of the early RA cytokine and IL-6 proinflammatory cytokine. 2. In case of EL-4 treated with Ulmus davidiana Planchon herbal acupuncture, there were decrease in the manifestation of the IL-2 mRNA, but the increase in the manifestation of the IL-4 does-dependently. 3. In the synovium of CIA mice treated with Ulmus davidiana Planchon herbal acupuncture, there were the decrease in generation of IL-2, IL-12 and CD-28, but the increase in generation of IL-4. These result suggest that Ulmus davidiana Planchon can block the process of the early RA by Inhibiting MIF activation, and mitigate Rheumatoid Arthritis by controlling Tcell specialization.

• Journal of Acupuncture Research
• /
• v.26 no.2
• /
• pp.159-170
• /
• 2009

Backgrounds and Objectives: A fracture means a loss of continuity in the substance of bone. Bone differs from other musculoskeletal tissue due to its ability to repair and heal itself without leaving a scar. The cutter head has multinucleated osteoclast cells to resorb the dead bone. The tail, with its conical surface, is lined with osteoblast cells laying down new bone. The conjugation of fracture is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Pyritum, one of the important prescriptions in the oriental medicine, has been used for conjugation fracture. The purpose of this study is to evaluate the effects of administration of Pyritum on activation of osteoblast cells in human body & on tibia bone fracture in mice. Materials and Methods : Four weeks aged 30 female DBA mice were used for this study. They were divided three groups, normal group, control group(fracture elicitate mice: FE group) and experimental group(Pyritum administered mice group after fracture elicitation : PA group). Left tibia bones of mice in FE and PA groups were fractured by bone cutters. MG-63 cells in human body th Pyritum in the ratio of 1 mg/m${\ell}$, and the cells were further incubated for 24 hours. Activation of osteoblast was identified using osteopontin, FGF in vitro test. In vivo test, regeneration of fractured tibia through the morphological changes was observed, and also activation of inflammation through NF-${\kappa}$B p65, iNOS, COX-2, osteoblast through osteopontin, FGF and osteoblast's proliferation in each group was measured. Results and Conclusions : 1. In vitro test for activation of osteoblast cells in human body by Pyritum, osteopontin and FGF production were remarkably increased in Pyritum treated MG-63 cells. 2. In regeneration of fractured tibia by Pyritum, fractured area in external tibia morphology was decreased more in the PA group than that of the FE group. Osteogenesis in fractured area was increased more in the PA group than that of the FE group. Also, endochodrial ossification in central area of fracture and osteoid in lateral area of fracture were increased more in the PA group than those of the FE group. 3. In activation of inflammation by Pyritum administered, activation of NF-${\kappa}$B p65, increase of iNOS and COX-2 production were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher activation and increase than those of the FE group. 4. In activation of osteoblast by Pyritum, increase of osteopontin, FGF and osteoblast's proliferation were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher increase and proliferation than those of the FE group.

• IMMUNE NETWORK
• /
• v.5 no.2
• /
• pp.78-88
• /
• 2005

Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.

• Korean Journal of Animal Reproduction
• /
• v.23 no.3
• /
• pp.247-256
• /
• 1999

The present study was performed to improve the reproductive disturbance as well as the elimination of microbiological contamination for animals bred under conventional conditions followed by in vitro fertilization and embryo transfer techniques including embryo and sperm freezing, using a mouse strain(M. m. molossinus-tt＠Kist) showing the abnormal behavior disorder derived from Korean wild mice (Mus musculus molossinus). Moreover, hematological and serum biochemical analyses were also carried out to obtain the basic data of this mouse strain The results are summarized as follows: 1. In comparison with hematological data, the numbers of RBC and platelet of this mouse strain were appeared as the higher value those that of the same aged inbred strains such as BALB/c, DBA/2, C57BL/6 and C3H /Hen. However, no differences were found in values of WBC, Hb and Ht. Moreover, total cholesterol of this strain showed a low value but triglyceride, total protein and albumin values were similar as in inbred strains. 2. The average numbers of superovulated oocytes treated with 2.5/2.5 IU and 5.0/5.0 IU of PMSG/hCG were 11.6 and 12.7, respectively. The fertilization rates of 2.5/2.5 IU PMSG /hCG treatment(87.9%) was higher than 5.0/5.0 IU treatment(52.0%) (p＜0.05) and the developmental rate of 2 cell stage embryos were 외 so appeared as higher value 99.0% and 90.6%, respectively. 3. The rates of in vitro fertilization treated with frozen sperm(24.8%) was significantly lower than of that fresh sperm(87.9%), (p＜0.05). 4. The five, six and ten heads of offspring were obtained from frozen-thawed 2 cell embryos by in vitro fertilized, 2 cell embryos from in vitro fertilized by frozen-thawed spermatozoa. and 2 cell embryos by in vitro fertilization, respectively. These offspring developed the expected disease about 2 weeks after birth, which was confirmed that the disease character of this mutant mouse strain was reliably reproduced. 5. MHV(Mouse hepatitis virus) and Staphylococcus aureus were successfully eliminated from conventional animals by in vitro fertilization-embryo transfer and the use of SPF recipient animals.

• Proceedings of the Korean Information Science Society Conference
• /
• 2007.06a
• /
• pp.17-18
• /
• 2007

데이터베이스 튜닝은 일반적으로 데이터베이스 어플리케이션을 "좀 더 빠르게" 실행하게 하는 일련의 활동을 뜻한다[1]. 데이터베이스 관리자가 튜닝에 필요한 주먹구구식 룰(Rule of thumb)들을 모두 파악 하고 상황에 맞추어 적용하는 것은 비싼 비용과 오랜 시간을 요구한다. 그렇게 때문에 서로 다른 어플 리케이션들이 맞물려 있는 복잡한 서비스는 필수적으로 자동화된 데이터베이스 성능 관리와 튜닝을 필 요로 한다. 본 논문에서는 이를 해결하기 위하여 지식 도매인(Knowledge Domain)을 기초로 한 자동화 된 데이터베이스 튜닝 원칙(Tuning Principle)을 제시하는 시스템을 제안한다. 각각의 데이터베이스 튜닝 이론들은 지식 도매인의 지식으로 활용되며, 성능에 영향을 미치는 요소들을 개체(Object)와 콘셉트 (Concept)로 구성하고 추론 시스템을 통해 튜닝 원칙을 추론하여 쉽고 빠르게 현재 상황에 맞는 튜닝 방법론을 적용시킬 수 있다. 자동화된 데이터베이스 튜닝에 대해 여러 분야에 걸쳐 학문적인 연구가 이루어지고 있다. 그 예로써 Microsoft의 AutoAdmin Project[2], Oracle의 SQL 튜닝 아키텍처[3], COLT[4], DBA Companion[5], SQUASH[6] 등을 들 수 있다. 이러한 최적화 기법들을 각각의 기능적인 방법론에 따라 다시 분류하면 크게 Design Tuning, Logical Structure Tuning, Sentence Tuning, SQL Tuning, Server Tuning, System/Network Tuning으로 나누어 볼 수 있다. 이 중 SQL Tuning 등은 수치적으로 결정되어 이미 존재하는 정보를 이용하기 때문에 구조화된 모델로 표현하기 쉽고 사용자의 다양한 요구에 의해 변화하는 조건들을 수용하기 쉽기 때문에 이에 중점을 두고 성능 문제를 해결하는 데 초점을 맞추었다. 데이터베이스 시스템의 일련의 처리 과정에 따라 DBMS를 구성하는 개체들과 속성, 그리고 연관 관계들이 모델링된다. 데이터베이스 시스템은 Application / Query / DBMS Level의 3개 레벨에 따라 구조화되며, 본 논문에서는 개체, 속성, 연관 관계 및 데이터베이스 튜닝에 사용되는 Rule of thumb들을 분석하여 튜닝 원칙을 포함한 지식의 형태로 변환하였다. 튜닝 원칙은 데이터베이스 시스템에서 발생하는 문제를 해결할 수 있게 하는 일종의 황금률로써 지식 도매인의 바탕이 되는 사실(Fact)과 룰(Rule) 로써 표현된다. Fact는 모델링된 시스템을 지식 도매인의 하나의 지식 개체로 표현하는 방식이고, Rule 은 Fact에 기반을 두어 튜닝 원칙을 지식의 형태로 표현한 것이다. Rule은 다시 시스템 모델링을 통해 사전에 정의되는 Rule와 튜닝 원칙을 추론하기 위해 사용되는 Rule의 두 가지 타업으로 나뉘며, 대부분의 Rule은 입력되는 값에 따라 다른 솔루션을 취하게 하는 분기의 역할을 수행한다. 사용자는 제한적으로 자동 생성된 Fact와 Rule을 통해 튜닝 원칙을 추론하여 데이터베이스 시스템에 적용할 수 있으며, 요구나 필요에 따라 GUI를 통해 상황에 맞는 Fact와 Rule을 수동으로 추가할 수도 었다. 지식 도매인에서 튜닝 원칙을 추론하기 위해 JAVA 기반의 추론 엔진인 JESS가 사용된다. JESS는 스크립트 언어를 사용하는 전문가 시스템[7]으로 선언적 룰(Declarative Rule)을 이용하여 지식을 표현 하고 추론을 수행하는 추론 엔진의 한 종류이다. JESS의 지식 표현 방식은 튜닝 원칙을 쉽게 표현하고 수용할 수 있는 구조를 가지고 있으며 작은 크기와 빠른 추론 성능을 가지기 때문에 실시간으로 처리 되는 어플리케이션 튜닝에 적합하다. 지식 기반 모률의 가장 큰 역할은 주어진 데이터베이스 시스템의 모델을 통하여 필요한 새로운 지식을 생성하고 저장하는 것이다. 이를 위하여 Fact와 Rule은 지식 표현 의 기본 단위인 트리플(Triple)의 형태로 표현된다, 트리플은 Subject, Property, Object의 3가지 요소로 구성되며, 대부분의 Fact와 Rule들은 트리플의 기본 형태 또는 트리플의 조합으로 이루어진 C Condition과 Action의 두 부분의 결합으로 구성된다. 이와 같이 데이터베이스 시스템 모델의 개체들과 속성, 그리고 연관 관계들을 표현함으로써 지식들이 추론 엔진의 Fact와 Rule로 기능할 수 있다. 본 시스템에서는 이를 구현 및 실험하기 위하여 웹 기반 서버-클라이언트 시스템을 가정하였다. 서버는 Process Controller, Parser, Rule Database, JESS Reasoning Engine으로 구성 되 어 있으며, 클라이 언트는 Rule Manager Interface와 Result Viewer로 구성되어 었다. 실험을 통해 얻어지는 튜닝 원칙 적용 전후의 실행 시간 측정 등 데이터베이스 시스템 성능 척도를 비교함으로써 시스템의 효용을 판단하였으며, 실험 결과 적용 전에 비하여 튜닝 원칙을 적용한 경우 최대 1초 미만의 전처리에 따른 부하 시간 추가와 최소 약 1.5배에서 최대 약 3배까지의 처리 시간 개선을 확인하였다. 본 논문에서 제안하는 시스템은 튜닝 원칙을 자동으로 생성하고 지식 형태로 변형시킴으로써 새로운 튜닝 원칙을 파생하여 제공하고, 성능에 영향을 미치는 요소와 함께 직접 Fact과 Rule을 추가함으로써 커스터마이정된 튜닝을 수행할 수 있게 하는 장점을 가진다. 추후 쿼리 자체의 튜닝 및 인텍스 최적화 등의 프로세스 자동화와 Rule을 효율적으로 정의하고 추가하는 방법 그리고 시스템 모델링을 효과적으로 구성하는 방법에 대한 연구를 통해 본 연구를 더욱 개선시킬 수 있을 것이다.