Biomedical subjects

L M Kirstein

Publications and source records attributed to L M Kirstein.

6 recordsLinked to original sources

PubMed2000

Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women.

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.

Adult↗

PubMed1999

Effects of anticoagulant, processing delay, and assay method (branched DNA versus reverse transcriptase PCR) on measurement of human immunodeficiency virus type 1 RNA levels in plasma.

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Alterations in blood-brain barrier glucose transport in SIV-infected macaques.

The neurological manifestations of HIV infection may be in part due to alterations in the blood-brain barrier. These may be caused by structural changes in the barrier or may consist of subtle metabolic or biochemical disturbances in barrier function. In the CNS, the family of glucose transporter proteins plays a key role in controlling movement of glucose across cell membranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-brain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulates nonvascular glial glucose uptake. In this study, expression of 55 and 45 kDa forms of GLUT1 in different regions of the brain from 18 SIV-infected macaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is related to altered glucose metabolism at the BBB and in brain parenchyma. An inverse relationship was found between severity of SIV encephalitis and expression of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical grey matter, caudate nucleus, and cerebellum. A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In addition, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques with moderate to severe encephalitis, 55 kDa GLUT1 expression had declined to pre-infection levels. These GLUT1 alterations at the BBB and in glial cells may reflect severe disturbances in the CNS microenvironment that contribute to CNS dysfunction.

Animals↗

PubMed1998

Identification of inflections in T-cell counts among HIV-1-infected individuals and relationship with progression to clinical AIDS.

Studies of circulating T (CD3(+)) lymphocytes have shown that on a population basis T-cell numbers remain stable for many years after HIV-1 infection (blind T-cell homeostasis), but decline rapidly beginning approximately 1.5-2.5 years before the onset of clinical AIDS. We derived a general method for defining the loss of homeostasis on the individual level and for determining the prevalence of homeostasis loss according to HIV status and the occurrence of AIDS in more than 5,000 men enrolled in the Multicenter AIDS Cohort Study. We used a segmented regression model for log10 CD3(+) cell counts that included separate T-cell trajectories before and after a time (the T-cell inflection point) where the loss of T-cell homeostasis was most likely to have occurred. The average slope of CD3(+) lymphocyte counts before the inflection point was close to zero for HIV- and HIV+ men, consistent with blind T-cell homeostasis. After the inflection point, the HIV+ individuals who developed AIDS generally showed a dramatic decline in CD3(+) cell counts relative to HIV- men and HIV+ men not developing AIDS. A CD3(+) cell decline of greater than 10 percent per year was present in 77% of HIV+ men developing AIDS but in only 23% of HIV+ men with no onset of AIDS. Our findings at the individual level support the blind T-cell homeostasis hypothesis and provide strong evidence that the loss of homeostasis is an important mechanism in the pathogenesis of the severe immunodeficiency that characterizes the late stages of HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Pathogenesis of simian immunodeficiency virus pneumonia: an immunopathological response to virus.

Although many human immunodeficiency virus-infected individuals develop lymphocytic interstitial pneumonia, the roles of host and viral factors in the pathogenesis of pneumonia are not well defined. Human immunodeficiency virus-infected children with lymphocytic interstitial pneumonia have human immunodeficiency virus-specific cytotoxic T cells in pulmonary infiltrates, increased survival time, and a reduced incidence of opportunistic infections, suggesting that lymphocytic interstitial pneumonia may reflect an effective antiviral immune response. In this study, 20 macaques were inoculated with related macrophage-tropic simian immunodeficiency viruses and examined for pulmonary lesions and virus gene expression. Ten macaques developed moderate to severe pneumonia characterized by perivascular, peribronchial, and interstitial infiltrates of lymphocytes and macrophages. Large numbers of pulmonary cytotoxic lymphocytes were demonstrated in macaques with moderate to severe pneumonia (P < 0.05) by immunostaining for TIA-1. There was no difference in viral load between macaques with moderate to severe pneumonia and those with mild to no pulmonary lesions. In five macaques inoculated with the same virus swarm, there was a significant (P < 0.05) inverse correlation between the percentage decline in CD4+ T-cell counts and the severity of pulmonary lesions. Pulmonary infiltrates of cytotoxic lymphocytes, the lack of correlation between severity of pulmonary lesions and virus gene expression, and the inverse relationship between pneumonia and inmune status suggest that simian immunodeficiency virus pneumonia may represent an immunopathological response to macrophage-tropic virus.

Animals↗

PubMed1997

Pathogenesis of simian immunodeficiency virus encephalitis: viral determinants of neurovirulence.

To examine the relationship between macrophage tropism and neurovirulence, macaques were inoculated with two recombinant hybrid viruses derived from the parent viruses SIVmac239, a lymphocyte-tropic, non-neurovirulent clone, and SIV/17E-Br, a macrophage-tropic, neurovirulent virus strain. The first recombinant, SIV/17E-Cl, contained the portion of the env gene that encodes the surface glycoprotein and a short segment of the transmembrane glycoprotein of SIV/17E-Br in the backbone of SIVmac239. Unlike SIVmac239, SIV/17E-Cl replicated productively in macrophages, demonstrating that sequences in the surface portion of env determine macrophage tropism. None of five macaques inoculated with SIV/17E-Cl developed simian immunodeficiency virus (SIV) encephalitis. The second recombinant, SIV/17E-Fr, which contained the entire env and nef genes and the 3' long terminal repeat of SIV/17E-Br in the SIVmac239 backbone, was also macrophage tropic. Six of nine macaques inoculated with SIV/17E-Fr developed SIV encephalitis ranging from mild to moderate in severity, indicating a significant (P = 0.031) difference in the neurovirulence of the two recombinants. In both groups of macaques, CD4+ cell counts declined gradually during infection and there was no significant difference in the rate of the decline between the two groups of macaques. This study demonstrated that macrophage tropism alone is not sufficient for the development of neurological disease. In addition, it showed that while sequences in the surface portion of the envelope gene determine macrophage tropism, additional sequences derived from the transmembrane portion of envelope and/or nef confer neurovirulence.

Animals↗