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An SIV/Macaque model of HIV-induced ...

Laast, Victoria.

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An SIV/Macaque model of HIV-induced peripheral nerve disease.

Record Type:	Electronic resources : Monograph/item
Title/Author:	An SIV/Macaque model of HIV-induced peripheral nerve disease./
Author:	Laast, Victoria.
Description:	114 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6186.
Contained By:	Dissertation Abstracts International67-11B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3240751
ISBN:	9780542955990

An SIV/Macaque model of HIV-induced peripheral nerve disease.
Laast, Victoria.

An SIV/Macaque model of HIV-induced peripheral nerve disease. - 114 p.

Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6186.

Thesis (Ph.D.)--The Johns Hopkins University, 2007.

HIV-1 infection is the causative agent of acquired immune deficiency syndrome (AIDS). Even with the introduction of highly active retroviral therapy (HAART) 3.1 million people infected with HIV-1 died in 2005, according to the WHO/UNAIDS AIDS epidemic update. The peripheral neuropathies are currently the most common neurological complication associated with HIV-1 infection, and distal sensory neuropathy (DSP) is the most common clinically significant form.

ISBN: 9780542955990Subjects--Topical Terms:

1017734
Biology, Microbiology.

An SIV/Macaque model of HIV-induced peripheral nerve disease.
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100 1 $a Laast, Victoria. $3 1917379
245 1 3 $a An SIV/Macaque model of HIV-induced peripheral nerve disease.
300 $a 114 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6186.
500 $a Advisers: Joseph Mankowski; M. Chris Zink.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2007.
520 $a HIV-1 infection is the causative agent of acquired immune deficiency syndrome (AIDS). Even with the introduction of highly active retroviral therapy (HAART) 3.1 million people infected with HIV-1 died in 2005, according to the WHO/UNAIDS AIDS epidemic update. The peripheral neuropathies are currently the most common neurological complication associated with HIV-1 infection, and distal sensory neuropathy (DSP) is the most common clinically significant form.
520 $a The pathogenesis of HIV-induced sensory neuropathy is not well defined. The lack of suitable animal models to study the underlying mechanisms of HIV-induced sensory neuropathy has been a major limitation. In this dissertation, I demonstrate that the SIV/macaque model is well suited to study the pathogenesis of HIV-induced peripheral nerve disease. I hypothesized that the pathological changes observed in the DRG would result in functional alterations in the conduction properties of peripheral sensory nerves. In these studies, I present evidence that the pathological changes that develop in the dorsal root ganglia (DRG) of SIV-infected macaques parallels alterations described in patients with DSP. This constitutes the first non-human primate model of HIV-induced peripheral nerve disease.
520 $a Skin biopsies have emerged as a valuable tool to diagnose small fiber sensory neuropathies including HIV-induced sensory neuropathy and diabetic neuropathy. In this dissertation, I demonstrate that epidermal nerve fiber density is reduced in SIV-induced peripheral neuropathy and that this reduction is associated with dorsal root ganglionitis severity. The uniqueness of this study was the implementation of a new method to quantitate epidermal nerve fiber density. I further show that slowing of conduction velocity in small sensory C-fibers develops in SIV-infected macaques and that this reduction in conduction velocity correlates strongly with extent of macrophage infiltration in the DRG and DRG neuronal density. Together these data on DRG and peripheral nerves suggest that the initiating event in HIV-induced peripheral neuropathy is in the DRG.
520 $a Finally, I show that minocycline in combination with an antiretroviral drug, 9-[(R)-2-phosphonylmethoxy) propyl] adenine (PMPA, Tenofovir), substantially lessens the severity of PNS disease in SIV-infected macaques.
520 $a In total, work in this dissertation identifies and characterizes an excellent animal model to study the pathogenesis of HIV-induced PNS disease.
590 $a School code: 0098.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Health Sciences, Pathology. $3 1017854
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0410
690 $a 0571
690 $a 0982
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 67-11B.
790 1 0 $a Mankowski, Joseph, $e advisor
790 1 0 $a Zink, M. Chris, $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3240751