東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁 到查詢結果 [ subject:"Biology, Genetics." ]

切換: 標籤 | MARC模式 | ISBD

Single-nucleotide polymorphisms in t...

The Johns Hopkins University.

FindBook

Google Book

Amazon

博客來

Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease./
作者:	Wright, Edward K., Jr.
面頁冊數:	110 p.
附註:	Adviser: Janice E. Clements.
Contained By:	Dissertation Abstracts International68-11B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3288557
ISBN:	9780549314042

Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease.
Wright, Edward K., Jr.

Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease. - 110 p.

Adviser: Janice E. Clements.

Thesis (Ph.D.)--The Johns Hopkins University, 2008.

Increased expression of CC-chemokine ligand 2 (CCL2) in the cerebrospinal fluid (CSF) and brain is consistently observed in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) central nervous system (CNS) disease. The molecular basis for the correlation between increased expression of CCL2 and HIV neuropathogenesis has been linked to a polymorphism at -2578 in the promoter of human CCL2, which was reported to influence the rate of progression to acquired immune deficiency syndrome (AIDS) and the predisposition of HIV-infected individuals to develop HIV-associated dementia (HIV-D). However, since the rate of neurological deterioration essentially parallels the progression of immunosuppression, it is inherently difficult to uncouple the influence of this polymorphism on increased progression to AIDS from increased propensity to develop CNS complications. Furthermore, no molecular mechanism has been associated with the -2578 polymorphism despite the association with HIV-D pathogenesis.

ISBN: 9780549314042Subjects--Topical Terms:

1017730
Biology, Genetics.

Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease.
LDR:03344nam 2200277 a 45 001 856587
005 20100709
008 100709s2008 ||||||||||||||||| ||eng d
020 $a 9780549314042
035 $a (UMI)AAI3288557
035 $a AAI3288557
040 $a UMI $c UMI
100 1 $a Wright, Edward K., Jr. $3 1023413
245 1 0 $a Single-nucleotide polymorphisms in the CCL2 promoter: Contribution to SIV/HIV central nervous system disease.
300 $a 110 p.
500 $a Adviser: Janice E. Clements.
500 $a Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7094.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2008.
520 $a Increased expression of CC-chemokine ligand 2 (CCL2) in the cerebrospinal fluid (CSF) and brain is consistently observed in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) central nervous system (CNS) disease. The molecular basis for the correlation between increased expression of CCL2 and HIV neuropathogenesis has been linked to a polymorphism at -2578 in the promoter of human CCL2, which was reported to influence the rate of progression to acquired immune deficiency syndrome (AIDS) and the predisposition of HIV-infected individuals to develop HIV-associated dementia (HIV-D). However, since the rate of neurological deterioration essentially parallels the progression of immunosuppression, it is inherently difficult to uncouple the influence of this polymorphism on increased progression to AIDS from increased propensity to develop CNS complications. Furthermore, no molecular mechanism has been associated with the -2578 polymorphism despite the association with HIV-D pathogenesis.
520 $a In this dissertation, we utilize our SIV macaque model and in vitro experiments with human U87-MG cells to examine the influence of variation in the CCL2 promoter on SIV/HIV CNS disease. First, we investigated variation in the CCL2 promoter of 29 pigtailed macaques examined in our SIV model and found that no variation correlated with the incidence or severity of CNS lesions or with levels of CCL2 in plasma or CSF, suggesting that the determinants of neuropathogenesis in this SIV model are distinct from variation in the CCL2 promoter/enhancer. Second, we investigated the relatedness of three species of macaque obtained from primate facilities that exhibit variable susceptibility to CNS disease in our model. Sequence analysis of the CCL2 promoter region and the gamma-globin-1 and gamma-globin-2 regions indicated that these three species of macaque are more closely related than previously appreciated. Finally, we propose a mechanism by which the -2578 human polymorphism regulates CCL2 expression, a finding significant to all studies investigating the role of the -2578 polymorphism to disease. We identified a complex consisting of Prep1 and Pbx2 that binds specifically to the -2578 G allele imposing a repressive phenotype on basal promoter activity. Immune stimulation relieves the repressive phenotype resulting in wild-type promoter activity and hence, a "hyper-responsive" CCL2 state.
590 $a School code: 0098.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 68-11B.
790 $a 0098
790 1 0 $a Clements, Janice E., $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3288557