• Title/Summary/Keyword: 면역 억제 치료

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Thioredoxin Peroxidase Manifestation in Radiation-Induced White Rat Lung Tissues (방사선 조사후 손상된 백서 폐조직에서의 Thioredoxin Peroxidase의 발현)

  • Chong, Seong-Cheoll;Park, Joon-Seong;Park, Jee-Won;Lee, Sun-Min;Park, Kwang-Joo;Hwang, Sung-Chul;Lee, Yi-Hyeong;Hahn, Myung-Ho;Oh, Young-Taek;Kim, Hyung-Joong
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.5
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    • pp.650-659
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    • 1999
  • Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

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Clinical Manifestation and Treatment Outcome of Lupus Nephritis in Children (소아 루프스 신염의 임상양상 및 치료결과)

  • Park Jee-Min;Shin Jae-Il;Kim Pyung-Kil;Lee Jae-Seung
    • Childhood Kidney Diseases
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    • v.6 no.2
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    • pp.155-168
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    • 2002
  • Purpose; Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-system involvement and renal damage is a major cause of morbidity and mortality in children. Renal involvement is more common and severe in children than in adults. Therefore, renal biopsy plays a crucial role in planning effective therapy. In this study, we investigated the clinical and pathological findings of lupus nephritis in children to aid clinical care of the disease. Methods: The clinical and pathological data of 40 patients who were diagnosed as SLE with renal involvement in Shinchon Severance Hospital from Jan. 1990 to Sep. 2002 were analyzed retrospectively. Results: The ratio of male to female patients was 1:3 and the median age at diagnosis was 12.1(2-18) years old. FANA(95.0%), anti-ds DNA antibody(87.5%), malar rash(80.0%) were the most common findings among the classification criteria by ARA. Microscopic hematuria with proteinuria(75.0%), nephrotic syndrome(55.0%), and microscopic hematuria alone(15.0%) were the most common renal presentations in the respective order at diagnosis. There were 27 cases with WHO class IV lupus nephritis confirmed by renal biopsy and 3 cases with pathological changes of WHO class type. Different treatment modalities were carried out : prednisolone only in 5 cases, prednisol-one+azat-hioprine in 9 cases, prednisolone+azathioprine+intravenous cyclophosphamide in 14 cases, prednisolone+cyclosporine A+intravenous cyclophosphamide in 12 cases, plasma exchange in 9 cases and intravenous gamma-globulin in 2 cases. The average follow-up period was $51.8{\pm}40.5$ months. During $51.8{\pm}40.5$ months. During follow-up, 4 patients expired. The risk factors associated with mortality were male, WHO class IV and acute renal failure at diagnosis. Conclusion: Renal involvement was noted in 63.5% of childhood SLE, and 67.5% of renal lesion was WHO class IV lupus nephritis which is known to be associated with a poor prognosis. Therefore aggressive treatment employing immunosuppressant during the early stages of disease could be helpful in improving long-term prognosis. But careful attention should be given to optimize the treatment due to unique problems associated with growth, psychosocial development and gonadal toxicity, especially in children.

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Effect of Flavopiridol on Radiation-induced Apoptosis of Human Laryngeal and Lung Cancer Cells (후두암 및 폐암 세포주에서 Flavopiridol이 방사선에 의한 아포토시스에 미치는 영향)

  • Kim, Su-Zy;Kwon, Eun-Kyung;Lee, Seung-Hee;Park, Hye-Jin;Wu, Hong-Gyun
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.227-232
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    • 2007
  • Purpose: To investigate the flavopiridol effect on radiation-induced apoptosis and expression of apoptosisrelated genes of human laryngeal and lung cancer cells. Materials and Methods: A human laryngeal cancer cell line, AMC-HN3 and a human lung cancer cell line, NCI-H460, were used in the study. The cells were divided into four groups according to the type of treatment: 1) control groups; 2) cells that were only irradiated; 3) cells treated only with flavopiridol; 4) cells treated with flavopiridol and radiation simultaneously. The cells were irradiated with 10 Gy of X-rays using a 4 MV linear accelerator. Flavopiridol was administered to the media at a concentration of 100 nM for 24 hours. We compared the fraction of apoptotic cells of each group 24 hours after the initiation of treatment. The fraction of apoptotic cells was detected by measurement of the sub-G1 fractions from a flow cytometric analysis. The expression of apoptosis-regulating genes, including cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), p53, p21, cyclin D1, and phosphorylated Akt (protein kinase B) were analyzed by Western blotting. Results: The sub-G1 fraction of cells was significantly increased in the combination treatment group, as compared to cells exposed to radiation alone or flavopiridol alone. Western blotting also showed an increased expression of cleaved caspase-3 and cleaved PARP expression in cells of the combination treatment group, as compared with cells exposed to radiation alone or flavopiridol alone. Treatment with flavopiridol down regulated cyclin 01 expression of both cell lines but its effect on p53 and p21 expression was different according to each individual cell line. Flavopiridol did not affect the expression of phophorylated Akt in both cell lines. Conclusion: Treatment with flavopiridol increased radiation-induced apoptosis of both the human laryngeal and lung cancer cell lines. Flavopiridol effects on p53 and p21 expression were different according to the individual cell line and it did not affect Akt activation of both cell lines.

Effects of Crormakalim on the Release of Mediators in Hypersensitivity of Guinea pig (Cromakalim이 해명의 과민반응 매개체 유리에 미치는 영향)

  • Ro, Jai-Youl;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.263-274
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    • 1993
  • Potassium $(K^+)$ channels are present in airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to hypersensitivity and asthma, we examined the effect of a potassium channel activator, cromakalim (BRL 34915, CK) on the release of mediators from superfused tracheal and parenchymal strips after passive sensitization with $IgG_1$ antibody. Both tissues were superfused with CK $(2{\times}10^{-6}\;M)$ for 30 min and challenged with CK and antigen (Ox-HSA). Using monodispersed, partially purified, highly purified guinea pig lung mast cells, we also examined the effect of CK on mediator release from these cells after passive sensitization with $IgG_{1}$ antibody $({\alpha}-OA)$. Guinea pig lung mast cells were purified using enzyme digestion method, count current elutriation, and discontinuous Percoll density gradient. After CK pretreatment, passively sensitized mast cells were challenged with varying concentration of antigen (OA, immunological stimuli) or with varying concentration of calcium ionophore (CaI, non-immunological stimuli). Histamine (Hist) release was determined by spectrophotofluorometry, and leukotrienes (LT) by radioimmunoassy. CK pretreatment decreased Hist by 35% and LT release by 40% in the antigen-induced tracheal tissue after $IgG_1$ sensitization but did not decrease the contractile response. In the antigen-induced parenchymal tissue CK decreased Hist release by 25% but poorly decreased LT. Both immunologic and non-immunologic stimuli caused a dose-dependent release of Hist and LT from monodispersed, partially purified and highly purified lung mast cells. Verification of LT release was obtained by the use of 5-lipoxygenase inhibitor, A64077 (Zileuton). CK decreased Hist and LT release by 20% respectively in the OA-induced guinea pig lung mast cells after $IgG_1$ sensitization. The inhibitory effects of CK on the Hist and LT release in the Ox-HSA-induced airway smooth muscle tissues or in the OA-induced and CaI-induced mast cells after $IgG_1$ sensitization were completely blocked by TEA and GBC. These studies show that guinea pig lung mast cells seem to be an important contributor to LT release, and that CK (which has been known as an airway smooth muscle relaxant) can in part act to inhibit mediator release in the antigen-induced airway smooth muscle, and that CK may also act to inhibit mediator release in the OA-induced and CaI-induced highly purified mast cells. These results suggest that Hist and LT release evoked by mast cell activation might in part be associated with $K{^+}4 channel activity.

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The Cytotoxic effects of several Herbs against human cancer cell-lines (수종(數種)의 한약재(韓藥材)가 인체(人體) 암세포주(癌細胞柱)에 미치는 세포(細胞) 독성(毒性))

  • Jeong, Hyeon-U
    • The Journal of Internal Korean Medicine
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    • v.18 no.1
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    • pp.231-241
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    • 1997
  • The purpose of this research was to investigate effect of water extract of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of human cancer cell-lines. The effects of Euphorbiae Pekinensis Radix and Moutan Cortex Radicis on the proliferation of A431, HeLa, MOLT-4, K562 cells, Balb/c 3T3 cells, mouse thymocytes, splenocytes and human lymphocytes were estimated by MTT colorimetric assay. The results were as follows; 1. In proliferation of A431, HeLa, MOLT-4 and K562 cell-lines, Euphorbiae Pekinensis Radix and Moutan Cortex Radicis inhibited the proliferation of K562 cells. 2. In the combined effect of Euphorbiae Pekinensis Radix and mitomycin C, Moutan Cortex Radicis and mitomycin C, all herbs stimulated the proliferation of MOL T-4 cells. 3. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis did not inhibited the proliferation of Balb/c 3T3 cells. 4. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse thymocytes. 5. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of mouse splenocytes. 6. Euphorbiae Pekinensis Radix and Moutan Cortex Radicis stimulated the proliferation of human lymphocytes.

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The Effect of Mixed Aroma Oil with Chamomile, Lavender and Sandalwood on Atopic Dermatitis in NC/Nga Mice (NC/Nga 마우스의 아토피 피부염에 미치는 카모마일, 라벤더, 샌달우드 혼합오일 도포의 치유효과)

  • Shin, Gil-Ran;Kim, Yang-Weon
    • Science of Emotion and Sensibility
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    • v.19 no.2
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    • pp.27-34
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    • 2016
  • The effects of aroma mixed oil with Chamomile, Lavender and Sandalwood on atopic dermatitis in NC/Nga mice were examined. The NC/Nga mice were divided into BMAC group, FK 506 Oinment (Tacrolimus Hydrate) group, and CLS group to get curative power of CLS. The amount of total IgE and IgG1 was measured and the severity of atopic dermatitis was assessed by the scoring procedure in NC/Nga mice. Topically applied CLS significantly suppressed the level of serum IgE and IgG1 in NC/Nga mice and FK506, used as reference drugs for atopic dermatitis, also exhibited suppressive effects against level of IgE and IgG1. The level of IgE was lower in the CLS group than in the FK506 group while the serum IgG1 level in the FK506 group was lower than in the CLS group. The treatment with FK506 and CLS reduced the skin inflammation index, especially the severity degree of atopic dermatitis in the skin lesioned NC/Nga mice by naked eyes was improved by treatment of FK506 and CLS. The results suggest that treatment of CLS in NC/Nga mice with atopic dermatitis have an beneficial therapeutic effects on reducing the level of IgE and IgG1 and accelerating repair of skin lesion.

Evaluation of the Radioimmunotherapy Using I-131 labeled Vascular Endothelial Growth Factor Receptor2 Antibody in Melanoma Xenograft Murine Model (흑색종에서의 I-131표지 혈관내피세포성장인자 수용체2항체를 이용한 방사면역치료 평가)

  • Kim, Eun-Mi;Jeong, Hwan-Jeong;Park, Eun-Hye;Cheong, Su-Jin;Lee, Chang-Moon;Jang, Kyu-Yun;Kim, Dong-Wook;Lim, Seok-Tae;Sohn, Myung-Hee
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.4
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    • pp.307-313
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    • 2008
  • Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

Anti-inflammatory Activity of Crinum asiaticum Linne var. Japonicum Extract and its Application as a Cosmeceutical Ingredient (문주란의 항염효과와 화장료적 특성)

  • Kim, Ki-Ho;Kim, Young-Heui;Kim, Ki-Soo;Park, Sun-Hee;Lee, Soo-Hee;Kim, Young-Jin;Kim, Young-Sil;Kim, Jong-Heon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.1 s.55
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    • pp.59-64
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    • 2006
  • Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

A Formulated Korean Red Ginseng Extract Inhibited Nitric Oxide Production through Akt- and Mitogen Activated Protein Kinase-dependent Heme Oxygenase-1 Upregulation in Lipoteichoic Acid-stimulated Microglial Cells (홍삼추출액은 lipoteichoic acid로 자극된 소교세포에서 Akt 및 MAPK 의존적으로 heme oxygenase-1 발현을 유도함으로써 NO 생성을 억제함)

  • Shin, Ji Eun;Lee, Kyungmin;Kim, Ji-Hee;Madhi, Iskander;Kim, YoungHee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.402-409
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    • 2019
  • Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.

Masticatory Muscle Myositis in a Maltese Dog (말티즈견에서 저작근염 발생례)

  • Kang, Byung-Jae;Rhew, Daeun;Kim, Yongsun;Lee, Seunghoon;Kim, Wan Hee;Kweon, Oh-Kyeong
    • Journal of Veterinary Clinics
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    • v.31 no.3
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    • pp.223-225
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    • 2014
  • A 8-year-old, castrated male Maltese with difficulty in opening his mouth was presented. Masticatory muscle myositis (MMM) was diagnosed by 2M antibody test. After treatment of MMM with corticosteroids, range of jaw motion improved and was almost normal at 5 months. In dogs with MMM, early detection and aggressive immunosuppressive therapy are required to improve the prognosis.