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Methylprednisolone 및 Levamisole 투여가 Bovine Gamma-Globulin으로 초래된 생쥐의 IgA 신병증에 미치는 영향
이광도,노은석,고철우,구자훈,송경은,김용진 慶北大學校 醫科大學 1996 慶北醫大誌 Vol.37 No.4
목적 : 본 연구는 생쥐를 대상으로 실험적 IgA 신병을 유발시키고 부신피질제재 및 levamisole 등의 면역제재를 투여하여 이들 약제의 IgA 신병증에 미치는 영향을 알아보고자 시행하였다. 대상 및 방법 : 실험동물은 체중 20-30gm 생쥐로서 암수 구별없이 사용하였다. 실험에 사용한 Bovine Gamma-Globulin (BGG, Sigma, U.S.A.)은 0.1% 농도로 식수에 섞어 매일 섭취시켰으며 제Ⅰ군은 BGG만을 섭취시켰고, 제Ⅱ군은 BGG섭취와 같은 시기부터 methylprednisolone을 격일로 존대를 통하여 경구 투여하였으며, 제Ⅲ군은 BGG 섭취와 같은 시기부터 levamisole을 격일로 존대를 통하여 경구 투여하였다. 실험 제 100일째 실험동물을 도살하고 신장을 적출하여 병리조직학적 검사를 시행하였다. 결과 : 실험개시후 100일째에 채취한 혈액검사상 혈청 BUN과 creatinine치는 각군간에 유의한 차이가 없었다. 병리조직학적 변화는 광학현미경 소견상 세군 모두에서 사구체의 미세한 변화만이 관찰되었다. 전자현미경적 소견은 세군 모두에서 기저막의 비후는 없었으며 족돌기도 잘 유지되어 있었다. 기저막쪽으로 향한 메산지움 영역에서 전자밀도가 높은 침착물이 흔히 관찰되었다. 면역형광현미경적 소견은 형광물질의 강약에 따라 약양성 (+), 중등도 양성 (++) 및 강양성(+++) 으로 구분하였다. 제Ⅰ군에서 형광물질은 IgA에서만 실험동물 9마리 모두에서 관찰되었다. 반면 IgM. IgG및 C_3는 모두 음성이었다. 면역형광물질은 모두 메산지움 및 기저막 일부에서 관찰되었으며 과립형이었다. 특히 강양성으로 보인 경우는 5마리였다. 제Ⅱ군에서도 결과는 같았으나 강양성은 20마리중 8마리였다. 역시 IgG, IgM, C_3는 음성이었다. 제 Ⅲ군에서도 결과는 같았으며 강양성은 20마리중 11마리였다. IgG, IgM은 모두 음성이었으며 단지 1마리에서 C_3가 약양성이었다. 결론 : 본 연구결과에 의하면 BGG투여로 초래되는 생쥐에서의 IgA 신병증의 실험모델에서는 methylprednisolone과 levamisole은 신장조직 소견상 IgA 침착정도나 병변의 경중에는 그 차이를 보이지 않았다. The pathogenesis of IgA nephropathy, first described by Berger and Hinglais in 1968. has not been defined clearly and appropriate treatment modality also not established. Present study has been conducted to induce IgA nephropathy in experimental animal and to see the effectiveness of methylprednisolone and levamisole on the experimentally induced IgA nephropathy. Mice weighing 20-30gm were used as experimental animal and Bovine gamma-globulin (BGG) (Sigma U.S.A.) was given as 0.1% drinking solution (Group Ⅰ). Group Ⅱ received methylprednisolone (5㎎/㎏) and Group Ⅲ levamisole (5㎎/㎏) on alternate day in addition to BGG-containing solution. On the 100th day of experiment, animals were sacrificed and blood chemistries and renal histopathologic examinations were done. Histopathologic examination: In all three groups, light microscopic, electron-microscopic and immunofluorescent microscopic findings were similar. Light microscopy showed mild focal mesangial proliferation and electron microscopy showed electron-dense materials deposited in the mesangial area near the basement membrane. Immuriofluorescent stain using fluorescin isothiocyanate goat anti-mouse IgA (Biodesign, U.S.A.) demonstrated prominent IgA staining in the mesangial area in all three group. Staining with IgG, IgM and C_3 were all negative. In conclusion, present experiment did not show any effectiveness of methylprednisolone nor levamisole on the BGG-induced IgA nephropathy in mice. And the effectiveness and its acting mechanism of methylprednisolone on human IgA nephropathy has to be studied further.
cDNA array 방법을 이용한 망간에 노출된 흰쥐 뇌기저핵의 유전자발현 분석
이채관,노성민,문덕환,,김정호,손병철,김대환,이창희,김휘동,김정원,김종은,안진홍,이채언 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4
Objectives: This study investigated the gene expression profile in basal ganglia of manganese-exposed rats based on cDNA array analysis. Methods: For cDNA array, 25 male Sprague-Dawley rats (250±25 g) were intraperitoneally injected with 25 ㎎/㎏ B. W./day of MnCl2 (0.3 ㎖) for 10 days. For dose-related gene expression analysis, rats were intraperitoneally injected with 0.2, 1.0, and 5.0 ㎎/㎏ B. W/day of MnCl2 for 10 days. Control rats were injected with an equal volume of saline. RNA samples were extracted from brain tissue and reverse-transcribed in the presence of [α^(32)P]-dATP. Membrane sets of the Atlas Rat 1.2 array Ⅱ and Toxicology array 1.2 kit (Clontech, Palo Alto, CA) were hybridized with cDNA probe sets. Northern blot hybridization method was employed to assess the dose-related gene expression. Results: Fifty-two genes showed significant changes in expression of more than two-fold. Twenty-eight were up-regulated and 24 were down-regulated in the manganese-exposed group compared to the control. Among the 52 genes, 28 genes including nuclear factor I-X1 (NF1-X1), neuroligin 2 and 3, mitochondrial stress-70 protein (MTHSP70), neurodegeneration-associated protein 1 (Neurodap 1), multidrug resistance protein (MDR), and endoplasmic reticulum stress protein 72 (ERP72), were reported for the first time related to the manganese-induced neurotoxic-metabolism in the rat basal ganglia. According to the dose-related gene expression analyses, MTHSP70, Neurodap 1 and ERP72 genes were up-regulated compared to the control even in the group exposed to low manganese dose ( 0.2 ㎎/㎏ B.W./day). Conclusions: Twenty-eight genes detected for the first time in this study were closely related to the manganese-induced neurotoxic-metabolism in the rat basal ganglia and further study of these genes can give some more useful information about the manganese metabolism.
Koo, Sun Hoe,Jeong, Tae Eun,Kang, Ji Un,Kwon, Kye Chul,Park, Jong Woo,Noh, Seung Moo 충남대학교 형질전환복제돼지연구센터 2004 논문집 Vol. No.8
In this study we used polymorphic DNA markers to examine 38 patients with gastric carcinoma for loss of heterozygosity(LOH) on five chromosomal arms. The aims were to compare LOH genotyping with the clinicopathologic variables and to identify some genetic differences between early (EGC) and advanced gastric carcinoma (AGC). The frequency of LOH was found in 27 of 38(71.1%) cases with a low-level LOH in 17(44.7%) and a high-level LOH(LOH-H) in 10(26.3%). There was statistical significance found in the differentiation of cells{WD/MD vs. PD[well or moderately differentiated vs. poorly differentiated]), metastasis {absent vs. present), and tumor-node-metastasis stage(Ⅰ/Ⅱ vs Ⅲ/Ⅳ) based on LOH genotyping. The frequency of LOH in the markers of chromosome 6 revealed a significant difference between the early and advanced stages(P=0.043). However, there were no differences in each chromosome or in the number of affected chromosomes with an allelic loss between the histologic types EGC and AGC, except for the frequency of the markers on chromosome 22. These findings suggest that LOH genotyping may be another independent prognostic indicator in gastric carcinoma, that LOH-H, particularly the LOH on chromosome6, could be associated with an unfavorable prognosis, while the LOH on chromosome 22 may be related to the histologic progression of gastric carcinoma.