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Transcriptional analysis of ex vivo ...

Huang, Li Ting.

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Transcriptional analysis of ex vivo granulocyte (neutrophil) development.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Transcriptional analysis of ex vivo granulocyte (neutrophil) development./
作者:	Huang, Li Ting.
面頁冊數:	260 p.
附註:	Advisers: E. Terry Papoutsakis; William M. Miller.
Contained By:	Dissertation Abstracts International67-10B.
標題:	Engineering, Biomedical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3237009
ISBN:	9780542908613

Transcriptional analysis of ex vivo granulocyte (neutrophil) development.
Huang, Li Ting.

Transcriptional analysis of ex vivo granulocyte (neutrophil) development. - 260 p.

Advisers: E. Terry Papoutsakis; William M. Miller.

Thesis (Ph.D.)--Northwestern University, 2006.

Transplantation of ex vivo expanded (EVE) granulocytic (neutrophil) precursors and progenitor cells can reduce and even eliminate high dose chemotherapy induced neutropenia. However, such therapy depends on the ability to consistently generate the necessary number of cells spanning various differentiation stages, which continues to be difficult to achieve. Although the effects of certain culture parameters, such as cytokines and pO2, are known, little is known about the molecular mechanisms by which they exert their influences, and the various mechanisms underlying the ex vivo granulocytic differentiation program. This has hindered development of effective culture techniques that allow for more effective and reliable control of culture outcomes.

ISBN: 9780542908613Subjects--Topical Terms:

1017684
Engineering, Biomedical.

Transcriptional analysis of ex vivo granulocyte (neutrophil) development.
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245 1 0 $a Transcriptional analysis of ex vivo granulocyte (neutrophil) development.
300 $a 260 p.
500 $a Advisers: E. Terry Papoutsakis; William M. Miller.
500 $a Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5897.
502 $a Thesis (Ph.D.)--Northwestern University, 2006.
520 $a Transplantation of ex vivo expanded (EVE) granulocytic (neutrophil) precursors and progenitor cells can reduce and even eliminate high dose chemotherapy induced neutropenia. However, such therapy depends on the ability to consistently generate the necessary number of cells spanning various differentiation stages, which continues to be difficult to achieve. Although the effects of certain culture parameters, such as cytokines and pO2, are known, little is known about the molecular mechanisms by which they exert their influences, and the various mechanisms underlying the ex vivo granulocytic differentiation program. This has hindered development of effective culture techniques that allow for more effective and reliable control of culture outcomes.
520 $a The transcriptional program of ex vivo granulocyte development was examined using DNA microarrays containing approximately 18,000 genes. Gene expression analysis identified the involvement of several transcription factors not previously associated with granulocytic development. Additionally, 13 candidate granule proteins were identified. The clinical potential of EVE granulocytes was further examined on a functional level. EVE granulocytes exhibited reduced phagocytic activity, which may be due to their expression and upregulation of only some phagocytosis-related genes. The amount of reactive oxygen species (ROS) produced through the process of respiratory burst varied with the stimulant used and the signaling pathway induced. Transcriptional analysis revealed possible explanations for the discrepancy in ROS levels produced by the three stimulants used. The degree of expression and upregulation of genes involved in pathways activated by each of the three stimulants directly corresponded to the level of ROS they induced. Finally, a comparison of the transcriptional programs underlying granulocytic and megakaryocytic development revealed a surprisingly high degree of similarity between the two. Furthermore, committed megakaryocytes at different stages of maturation were reprogrammed into granulcoytes by simply re-culturing them in a medium normally used to induce granulocytic development.
520 $a The findings obtained through this study provide important insights into the mechanisms and regulators of granulocyte commitment and development, as well as the transdifferentiation potential of committed hematopoietic cells. Such knowledge may aid in understanding, diagnosing and treating various granulocytic disorders. Additionally, it can be utilized to develop methods to increase productivity and control of granulocytic cultures.
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