• Title/Summary/Keyword: NIH

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Decreased Interaction of Raf-1 with Its Negative Regulator Spry2 as a Mechanism for Acquired Drug Resistance

  • Ahn, Jun-Ho;Kim, Yun-Ki;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.174-180
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    • 2011
  • Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance to paclitaxel in v-H-ras transformed NIH 3T3 fibroblasts (Ras-NIH 3T3). We established a multidrug-resistant cell line (Ras-NIH 3T3/Mdr) from Ras-NIH 3T3 cells by stepwise increases in paclitaxel. Drug sensitivity assays indicated that the $IC_{50}$ value for drug-resistant Ras-NIH 3T3/Mdr cells was more than 1 ${\mu}M$ paclitaxel, 10- or more-fold higher than for the parental Ras-NIH 3T3 cells. Western blot and RT-PCR analysis showed that the drug efflux pump a P-glycoprotein were highly expressed in Ras-NIH 3T3/Mdr cells, while not being detectable in Ras-NIH 3T3 cells. Additionally, verapamil, which appears to inhibit drug efflux by acting as a substrate for P-glycoprotein, completely reversed resistance to paclitaxel in Ras-NIH 3T3/Mdr cell line, indicating that resistance to paclitaxel is associated with overexpression of the multidrug resistance gene. Interestingly, Ras-NIH 3T3/Mdr cells have higher basal Raf-1 activity compared to Ras-NIH 3T3 cells. Unexpectedly, however, the colocalization of Raf-1 and its negative regulator Spry2 was less observed in cytoplasm of Ras-NIH 3T3/Mdr cells due to translocation of Spry2 around the nucleus in the perinuclear zone, implying that Raf-1 may be released from negative feedback inhibition by interacting with Spry2. We also showed that shRNA-mediated knockdown of Raf-1 caused a moderate increase in cell susceptibility to paclitaxel. Thus, the results presented here suggest that a Raf-1-dependent pathway plays an important role in the development of acquired drug-resistance.

A Study on the Improvement Plan of Public Health Official Training (보건분야 공무원 교육훈련 현황 및 발전 방안에 관한 연구)

  • Shin, Young-Hack;Yoon, Young-Hee;Kim, Jee-Hee;Ahn, Chang-Yeoung;Kim, Jeum-Ja;Lee, Jong-Mu;Lee, Soon-Yeon;Kim, Myung-Hyun;Yang, Sook-Ja
    • Research in Community and Public Health Nursing
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    • v.14 no.3
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    • pp.533-545
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    • 2003
  • Purpose: This study investigated the situation of public health official training and suggested a scheme for improving central and local official training institutes, in order to improve the quality and quantity of training programs for central and local public health officials. Methods: This study examined training resources, design processes, content and methods of training programs of the Department of Health and Welfare Training in NIH and the fifteen city and provincial officials training institutes in 2002. Results: The central and the local officials training institutes didn't exchange information on public health training. NIH supplied various specialized training programs for senior and junior officials. However, city and provincial official training institutes supplied a few training programs for local public health officials. Conclusion: A mutually cooperative relationship is needed between central and local official training institutes to exchange information on public health official training. The Department of Health and Welfare Training in NIH as a central training institute has to develop training programs related to new public health policies, supply training programs for senior officials, and support local official training institutes. To satisfy the training demands of public health officials, the city and provincial official training institutes should increase the number of training programs for junior officials.

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Up-regulation of dynamin-2 gene expression in Ras-transformed cells (Ras에 의해 암화된 세포에서 dynamin-2의 발현 촉진)

  • Yoo, Ji-Yun
    • Journal of Life Science
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    • v.17 no.3 s.83
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    • pp.375-380
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    • 2007
  • Dynamin plays a key role in the scission event common to various types of endocytosis. It has been previously reported that the SH3 domain-mediated association of Grb2 with dynamin-2 was dominantly found in Ras transformed cells. However, whether this association results from the increased expression of dynamin-2 and Grb2 in Ras transformed cells or not is still unknown. So in this study we first analyzed the expression levels of dynamin-2 and Grb2 and found that the expression of dynamin-2 protein was dramatically increased in Ras-transformed NIH3T3 (NIH3T3(Ras)) cells. Furthermore competitive PCR data revealed that the mRNA transcripts for dynamin-2 were increased about 100-fold in NIH3T3(Ras) compared to those of NIH3T3 cells. However, the protein level and mRNA transcript of Grb2 were not changed in these two cells. We also examined promoter activity of dynamin-2 in NIH3T3(Ras) cells and suggest the existence of Ras-responsive sequence in promoter region -300 to -200.

Differential expression patterns of gangliosides in the tissues and cells of NIH-mini pig kidneys

  • Cho, Jin-Hyoung;Kim, Ji-Su;Lee, Young-Choon;Oh, Keon-Bong;Kwak, Dong-Hoon;Kim, Won-Sin;Hwang, Seong-Soo;Ko, Ki-Sung;Chang, Kyu-Tae;Choo, Young-Kug
    • Animal cells and systems
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    • v.14 no.2
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    • pp.83-89
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    • 2010
  • Gangliosides are a ubiquitous component of the membranes of mammalian cells that have been suggested to play important roles in various cell functions such as cell-cell interaction, adhesion, cell differentiation, growth control and signaling. However, the role that gangliosides play in the immune rejection response in xenotransplantation is not yet clearly understood. In this study, differential expression patterns of gangliosides in HEK293 (human embryonic kidney cells), PK15 (porcine kidney cells), NIH-kd (NIH-mini pig kidney cells, primary cultured) and the cortex, medulla and calyx of the NIH-mini pig kidney were investigated by high-performance thin-layer chromatography (HPTLC). The results revealed that HEK293, PK15 and NIH-kd contained GM3, GM2 and GD3 as major gangliosides. Moreover, GM3, which are the gangliosides of NIH-kd, were expressed at higher levels than HEK293 and PK15. Especially, GT1b were expressed in HEK293 and NIH-kd but not in PK15. Finally, GM1 and GD1a were expressed in NIH-kd, but not in HEK293 or PK15. These results suggest that differential expression patterns of gangliosides from HEK293, PK15 and NIH-kd are related to the immune rejection response in xenotransplantation.

Dynamin II Expression and Morphological Comparison of NIH3T3 and NIH3T3 (ras) Cells (NIH3T3와 NIH3T3(ras) 세포에서 Dynamin II 발현 및 형태적 비교)

  • Lee, Chul-Woo;Kim, Su-Gwan;Choi, Jeong-Yun;Choi, Baik-Dong;Bae, Chun-Sik;Jeong, Soon-Jeong;Jeong, Moon-Jin
    • Applied Microscopy
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    • v.35 no.3
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    • pp.121-128
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    • 2005
  • It has been known that ras signaling transduction leads to cell proliferation and migration including various adaptor molecules. Dynamin protein has been implicated in the formation of nascent vesicles in both the endocytic and secretory pathways. Dynamin was classified into three isoforms: dynamin I is only expressed in neuronal tissue, dynamin II is expressed ubiquitously in all tissue but that of dynamin III is confined to testis. We have reported in previous study that Grb2, binding to ras, was associated with dynamin II in NIH3T3 cells. Therefore we have tried to identify the relative expression of dynamin II according to overexpressed ras protein in ras oncogene transfected cells (NIH3T3 (ras)). For the detection of differential expression of dynamin II, we have used immunofluorescent staining and western blot methods in NIH3T3 and NIH3T3 (ras) cells. Next we have described the morphological differences between NIH3T3 and NIH3T3 (ras) cells using SEM and TEM. From these experiments dynamin II was highly expressed in NIH3T3 (ras) cells. NIH3T3 cells was transformed to more spindle shape with many cell process by transfection of ras oncogene. Moreover dynamin II was more concentrated in endocytotic membrane of the NIH3T3 (ras) cells compared to that of NIH3T3 cells. The present results suggested that dynamin II may involve the intermediate messenger in Ras signaling transduction pathway.

미국의 국립보건연구원

  • Kim, Heon-Gyu
    • The Science & Technology
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    • v.2 no.3 s.7
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    • pp.65-70
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    • 1969
  • 1.NIH의 사명 2.NIH의 역사 3.NIH의 행정기구 4.직속의학연구소 개황 5.해외보건연구협조처

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