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1.
J Neuropathol Exp Neurol ; 60(9): 885-92, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11556545

ABSTRACT

We employed laser capture microdissection to remove individual pyramidal neurons from the CA1, CA3, and CA4 regions of formalin-fixed, paraffin-embedded hippocampus from 8 AIDS brains and 2 HIV-1-seronegative normal brains. We amplified HIV-1 gag and nef gene sequences using separate, double round PCR reactions for each of the primer sets. In all 3 hippocampal regions, amplification efficiency was best with sequence length between 284 and 324 bp; HIV-1 nef gene sequences were more common than HIV-1 gag sequences; and rank order for percent positive amplification was CA3 > CA4 > CA1 samples. These results are the first to detect HIV-1 gene sequences in microdissected human tissue. They indicate that brain neurons in vivo contain HIV-1 DNA sequences consistent with latent infection by this virus, and suggest that neurons display a selective vulnerability for HIV infection. Neuronal HIV infection could contribute to neuronal injury and death or act as a potential viral reservoir if reactivated.


Subject(s)
AIDS Dementia Complex/pathology , AIDS Dementia Complex/virology , HIV-1/isolation & purification , Hippocampus/pathology , Neurons/pathology , Adult , Astrocytes/pathology , Astrocytes/virology , Child , DNA Primers , DNA, Viral/analysis , Female , Gene Products, gag/genetics , Gene Products, nef/genetics , HIV-1/genetics , Hippocampus/virology , Humans , Infant , Lasers , Male , Neurons/virology , Polymerase Chain Reaction , nef Gene Products, Human Immunodeficiency Virus
2.
Brain Res ; 888(2): 297-301, 2001 Jan 12.
Article in English | MEDLINE | ID: mdl-11150487

ABSTRACT

Since clusterin (CLU) production in reactive astrocytes may be neuroprotective, we examined its distribution in AIDS brains where brain injury and reactive astrocytosis are common. The relative area and number of CLU-positive astrocytes, as well as their percent total of all white matter glia, significantly increased in AIDS brains with and without HIV encephalitis (P<0.05). Proliferation markers were absent. In contrast, the relative area and number of GFAP-positive astrocytes and their percent of all white matter glia, increased in some cases but the mean increases were not significant. Clusterin is sensitive marker of glial reactivity in AIDS brains and its enhanced expression was not dependent on increases in GFAP.


Subject(s)
AIDS Dementia Complex/metabolism , Acquired Immunodeficiency Syndrome/metabolism , Frontal Lobe/metabolism , Glycoproteins/metabolism , Molecular Chaperones/metabolism , Neuroglia/metabolism , AIDS Dementia Complex/etiology , AIDS Dementia Complex/pathology , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/pathology , Adult , Astrocytes/metabolism , Astrocytes/pathology , Clusterin , Female , Frontal Lobe/pathology , Glial Fibrillary Acidic Protein/metabolism , Glycoproteins/genetics , Humans , Immunohistochemistry , In Situ Hybridization , Ki-67 Antigen/metabolism , Male , Middle Aged , Molecular Chaperones/genetics , Neuroglia/pathology , Neurons/metabolism , Neurons/pathology , RNA, Messenger/metabolism , Up-Regulation
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