Monitoring HIV-1 treatment in immune-cell subsets with ultrasensitive fluorescence-in-situ hybridisation.
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Anti-HIV Agents↗
Biomedical subjects
B K Patterson
Publications and source records attributed to B K Patterson.
Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.
HIV-1 transmission and disease progression is, in general, characterized by initial predominance of macrophage tropic, non-syncytium-inducing strains followed by a switch to T-cell tropic, syncytium-inducing strains. Using sensitive, quantitative kinetic RT-PCR, we examined cytokine regulation of tropism-specific HIV-1 coreceptor expression in PBMCs from HIV-1-seronegative individuals. Proinflammatory (TNF-alpha and IL-12) and type 1 cytokines (IFN-gamma and IL-2) significantly upregulated CCR5 (wt allele) mRNA expression in CCR5 homozygous wild-type (wt/wt) and heterozygous individuals (wt/del) (P < 0.02). CCR5 (wt) mRNA expression in unstimulated PBMCs was significantly increased in wt/wt individuals compared to that of wt/del individuals (P < 0.01). In wt/del individuals, del CCR5 mRNA was expressed at 10-fold greater levels than wt CCR5 mRNA in unstimulated PBMCs from the same individual. Flow cytometry confirmed that upregulated CCR5 mRNA following type 1 cytokine stimulation leads to increased cell surface expression of CCR5 protein. The type 2 cytokine IL-10 downregulated both CCR5 mRNA and protein expression in wt/wt and wt/del individuals. Proinflammatory, type 1, and type 2 cytokines significantly increased CXCR4 mRNA expression in wt/wt, wt/del, and del/del CCR5 genotypes (P < 0.02). These results suggest that changes in the cytokine milieu influence chemokine receptor expression and may explain emergence of tropism-specific strains facilitating HIV transmission and disease progression.
Base Sequence↗
In vivo migration and function of transferred HIV-1-specific cytotoxic T cells.
The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8+ cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8+ CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo, accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4+ T cells. These results provide direct evidence that HIV-specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection.
Adoptive Transfer↗
Early reduction of immune activation in lymphoid tissue following highly active HIV therapy.
OBJECTIVE: To evaluate immune reconstitution within HIV-infected lymphoid tissue during highly active antiretroviral therapy (HAART). DESIGN AND METHODS: In situ cellular responses were studied in sequential tonsillar biopsies in three asymptomatic HIV-infected (CD4 cells greater than 400 x 10(6)/l) antiretroviral treatment-naive volunteers enrolled in a clinical trial to determine the early effect of HAART. Computerized image analysis was used to study immunohistochemically stained sequential tonsil sections for the patterns of local cytokine production, chemokine receptor expression and cellular distribution. Replicate quantitative assessments of samples before and after 4 weeks of therapy were used for the evaluation of drug effects and compared with four uninfected controls. Tonsillar HIV proviral-DNA was determined by fluorescent in situ 5'-nuclease assay. RESULTS: HIV-infected tonsil tissue was characterized by extensive pro-inflammatory and type 1 cytokine expression. A five- to 15-fold elevation of interleukin (IL)-1 alpha, IL-12, IL-2 and interferon (IFN)-gamma protein expression was found compared with controls, and each encompassed a mean of at least 4.5% of the tissue compartment. This was reduced by 20-90% in all individuals after 4 weeks of HAART. In contrast, type 2 cytokine expression (IL-4, IL-10), plus tumour necrosis factor (TNF)-alpha, remained low throughout the study. HAART reduced, by 40%, the expression of HIV co-receptors, CCR5 and CXCR4, which initially were elevated four to six times over the control values. In addition, the myelomonocytic inflammatory proteins, CD68 and calprotectin, diminished by 26-83% after therapy. The HIV RNA was reduced to undetectable levels in plasma by HAART. However, a large pool of tonsil cells (2-7%), remained HIV DNA positive after 4 weeks of therapy. CONCLUSIONS: Although immune activation may be the direct consequence of HIV replication, HAART-associated reconstitution begins with a reduction in inflammatory cytokine production which precedes the elimination of local proviral reservoirs.
Anti-HIV Agents↗
Productive infection of neonatal CD8+ T lymphocytes by HIV-1.
CD8+ T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here we report that activated neonatal CD8+ T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whereas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta+ CD4- T cell receptor-alpha/beta+ neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1-activated cord blood CD8+ T cells coexpress CD4, the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8+ T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation.
CD4 Antigens↗
Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype.
Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.
Cell Line↗
Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission.
Sexually transmitted diseases, genital ulcer disease, and progesterone therapy increase susceptibility to lentivirus transmission. Infection of cells by human immunodeficiency virus (HIV) is dependent on expression of specific chemokine receptors known to function as HIV co-receptors. Quantitative kinetic reverse transcription-polymerase chain reaction was developed to determine the in vivo expression levels of CCR5, CXCR4, CCR3, CCR2b, and the cytomegalovirus-encoded US28 in peripheral blood mononuclear cells and cervical biopsies from 12 women with and without sexually transmitted diseases, genital ulcer disease, and progesterone-predominant conditions. Our data indicate that CCR5 is the major HIV co-receptor expressed in the female genital tract, and CXCR4 is the predominantly expressed HIV co-receptor in peripheral blood. CCR5 mRNA expression in the ectocervix was 10-fold greater than CXCR4, 20-fold greater than CCR2b, and 100-fold greater than CCR3. In peripheral blood, CXCR4 expression was 1.5-fold greater than CCR5, 10-fold greater than CCR2b, and 15-fold greater than CCR3. US28 was not expressed in cervical tissue despite expression in peripheral blood mononuclear cells from five individuals. CCR5 was significantly increased (p < 0.02) in biopsies from women with sexually transmitted diseases and others who were progesterone predominant. In vitro studies demonstrate that progesterone increases CCR5, CXCR4, and CCR3 expression and decreases CCR2b expression in lymphocytes and monocytes/macrophages. Characterization of chemokine receptors at the tissue level provides important information in identifying host determinants of HIV-1 transmission.
Adult↗
Cellular localization of latent murine cytomegalovirus.
Herpesviruses typically establish latent infection in their hosts. The cell(s) responsible for harboring latent virus, in most cases, is not known. Using immunofluorescence and PCR-in situ hybridization (PISH), a technique which combines the sensitivity of PCR with the localization and specificity of in situ hybridization, we provide the first direct evidence that endothelial cells are a major site of murine cytomegalovirus (MCMV) DNA in latently infected animals. These findings are consistent with existing knowledge of the biological behavior of CMV, in particular the transmission of latent CMV by solid organ and bone marrow transplantation, in both human and animal models. In addition, we have localized MCMV DNA in the lung alveolar macrophage and in bone marrow cells. Our findings confirm that bone marrow-derived hematopoietic cells are a site of CMV latency and further suggest that bone marrow may be a reservoir of infected progeny capable of migrating into the circulation and establishing latency in various tissues. These findings provide clearly needed insight into the site of latent infection which is central to an understanding of the mechanisms of reactivation.
Animals↗
Reducing cellular autofluorescence in flow cytometry: an in situ method.
Cellular autofluorescence affects the sensitivity of flow cytometric assays by interfering with detection of low level specific fluorescence. These detection limits increase with use of protocols, such as thermocycling and fluorescent in-situ hybridization (FISH), that can increase intrinsic cellular fluorescence to 5,000-20,000 fluorescein isothiocyanate (FITC) equivalents. In order to improve signal to noise ratios when using FITC labeled probes in these procedures, we employed a method using the polyanionic azo dye, trypan blue, to reduce intracellular autofluorescence. Dyes such as these are commonly used in immunofluorescent microscopy to reduce background fluorescence. By using this method, we realized an approximately 5-fold increase in signal to noise ratio (S/N) in the direct detection of RNA target probes using flow cytometry. Trypan blue aided in the resolution of dim surface antibodies, internal markers and probes, and functions to reduce background autofluorescence after thermocycling and hybridization. This technique is rapid and easily applicable for reducing intracellular autofluorescence, and can be used in single and dual color applications.
Coloring Agents↗
Detection of HIV-1 DNA in cells and tissue by fluorescent in situ 5'-nuclease assay (FISNA).
The critical aspects of successful in situ amplification include fixation, permeabilization, amplification and detection. We address these aspects and present a novel detection scheme that eliminates hybridization following amplification. We use the 5'-nuclease activity of Taq polymerase to cleave in situ a 5'-reporter dye from an oligonucleotide probe which hybridizes to the target amplicon during amplification. The 5'-reporter dye is disassociated from the 3'-quenching dye and remains localized by charge interactions. In addition, we describe probe design constraints for 5'-nuclease assays both in solution and in situ. Using this technique, we show the sensitive and specific detection of HIV-1 DNA in cells lines and tissue from HIV-1-infected individuals.
5'-Nucleotidase↗
Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques.
We used the simian immunodeficiency virus (SIV)/rhesus macaque model to study events that underlie sexual transmission of human immunodeficiency virus type 1 (HIV-1). Four female rhesus macaques were inoculated intravaginally with SIVmac251, and then killed 2, 5, 7, and 9 d later. A technique that detected polymerase chain reaction-amplified SIV in situ showed that the first cellular targets for SIV were in the lamina propria of the cervicovaginal mucosa, immediately subjacent to the epithelium. Phenotypic and localization studies demonstrated that many of the infected cells were likely to be dendritic cells. Within 2 d of inoculation, infected cells were identified in the paracortex and subcapsular sinus of the draining internal iliac lymph nodes. Subsequently, systemic dissemination of SIV was rapid, since culturable virus was detectable in the blood by day 5. From these results, we present a model for mucosal transmission of SIV and HIV-1.
Animals↗
Elevated levels of plasminogen-activator inhibitor type 1 in atherosclerotic aorta.
PURPOSE: Plasminogen activator inhibitor type I (PAI-1) inhibits the plasminogen activators that convert plasminogen to plasmin. In addition to initiating fibrinolysis, plasmin activates tissue matrix metalloproteinases, which cause degradation of the extracellular matrix (ECM) in the arterial wall. Elevated levels of PAI-1 ultimately decrease plasmin formation and may lead to an accumulation of ECM and arteriosclerosis. METHODS: PAI-1 was studied by four methods in atherosclerotic (aneurysmal and occlusive) and normal (organ donor) aorta: (1) PAI-1 secretion by tissue explant supernatants, including time course and inhibition studies; (2) tissue PAI-1 by protein extraction; (3) PAI-1 mRNA was quantitated by Northern analysis using glyceraldehyde-3-phosphate dehydrogenase to normalize for RNA loading; and (4) in situ hybridization was used to localize the cells that produced PAI-1 mRNA. RESULTS: Supernatant PAI-1 levels at 48 hours were 776 +/- 352, ng/ml in 11 atherosclerotic aortas and 248 +/- 98 ng/ml in 8 normal aortas (p < 0.005). Tissue PAI-1 levels per 100 mg of tissue were 99 +/- 58 ng in 11 atherosclerotic aortas and 38 +/- 20 ng in 5 normal aortas (p < 0.05). PAI-1 mRNA levels by Northern analysis were 0.91 +/- 0.49 in seven atherosclerotic aortas and 0.44 +/- 0.27 in five normal aortas. Supernatant time-course experiments revealed that PAI-1 increased over time. Inhibitor studies revealed that PAI-1 decreased to approximately one third of control values when cycloheximide or actinomycin D were added to the media, indicating that active synthesis of PAI-1 had occurred. In-situ hybridization localized PAI-1 mRNA predominately to endothelial cells and a few scattered vascular smooth muscle and inflammatory cells. Subgroup analysis revealed no statistically significant differences between aneurysmal and occlusive PAI-1 levels in any of the experiments. CONCLUSION: PAI-1 secretion, as measured by tissue explant supernatants, and total tissue PAI-1 in the protein extracts were significantly increased in atherosclerotic aorta. This elevation was also observed in the mRNA, which suggests that the increase is controlled at the level of transcription. PAI-1 mRNA was localized to endothelial, vascular smooth muscle, and inflammatory cells. We conclude that elevated levels of PAI-1 exist in diseased aorta. These elevated levels may lead to an accumulation of ECM, thereby contributing to the arteriosclerosis found in aortic occlusive and aneurysmal disease.
Adult↗
CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells.
Most human immunodeficiency virus (HIV)-infected individuals show evidence of infection by only one strain of the virus despite possible frequent contact with multiple strains. The reason(s) for the emergence of a dominant strain of virus in HIV-infected people and the mechanism(s) which prevent other strains from establishing an infection is not known. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of asymptomatic HIV-infected individuals can resist productive infection by HIV-1 and HIV-2 strains. Although the PBMC of these individuals are resistant to superinfection, their CD4+ cells are susceptible to infection. Moreover, two weeks after infection of their PBMC in culture, the superinfecting virus can be recovered from isolated CD4+ cells. When CD8+ cells from asymptomatic individuals are added to the superinfected CD4+ cells, replication of the exogenously introduced virus is inhibited. In contrast, PBMC from individuals who have progressed to disease (Progressors) do not resist superinfection and their CD8+ cells do not showthe antiviral activity which controls productive HIV infection. These findings suggest that CD8+ cells suppressing HIV replication in infected individuals may be critical in preventing the establishment of infection by other strains of HIV by blocking virus replication.
CD4-Positive T-Lymphocytes↗
Inhibition of anti-V3 domain antibody binding to human immunodeficiency virus type-1-infected cells by sulfated polysaccharides.
The third variable domain (V3 domain) of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is an immunodominant region. Anti-V3 domain antibodies neutralize both HIV-1 infection and syncytium formation. The V3 domain has a high density of positive charge which is a potential binding site for anti-HIV-1 sulfated polysaccharides. To investigate the inhibitory effect of sulfated polysaccharides on the binding of anti-V3 domain antibody, fluorescence-activating cell sorting analysis was performed using two kinds of antibodies, NEA9284 (purified, 0.25 micrograms/ml) and 0.5 beta (ascite, 2.0 mg/ml), and HIV-1-infected CEM cells. When the binding assay with a 1:100 dilution of each antibody was performed in the presence of dextran sulfate, heparin, and inositol hexasulfate at concentrations which are antiviral, the compounds did not inhibit the binding of either antibody. As the antibody concentration was decreased with higher dilution, dextran sulfate was able to reduce antibody binding by 50-60%. Thus, antagonism of anti-V3 domain antibody binding by sulfated polysaccharides is not as extensive as reported previously by several groups.
Amino Acid Sequence↗
In situ localization and quantification of seventy-two-kilodalton type IV collagenase in aneurysmal, occlusive, and normal aorta.
PURPOSE: Seventy-two-kilodalton type IV collagenase (MMP-2), a potent collagenase and elastase, is present in inflammatory disease states and may be important in the pathogenesis of aortic aneurysms. Alteration in expression of MMP-2 or its inhibitor, the tissue inhibitor of metalloproteinases type two (TIMP-2), could increase extracellular matrix degradation and lead to aneurysm formation. The purpose of this study is (1) to measure relative tissue levels of MMP-2 and TIMP-2 mRNA in aneurysmal, occlusive, and normal human infrarenal aorta; (2) to test for expression by cultured aneurysmal and normal vascular smooth muscle cells (VSMCs); and (3) to identify, in situ, the cells responsible for mRNA production within aneurysmal, occlusive, and normal aortic wall. METHODS: Total RNA extracted from aneurysmal (n = 8), occlusive (n = 9), and normal (n = 7) tissue was subjected to Northern analysis. Signals for MMP-2 and TIMP-2 were normalized to alpha-tubulin. Mean values +/- SE were compared by use of analysis of variance. Aneurysmal and normal VSMCs were cultured, passaged, and grown to confluence before RNA extraction and Northern analysis. In situ hybridization with digoxigenin RNA probes localized cells responsible for MMP-2 and TIMP-2 mRNA production in histologic sections of aneurysmal (n = 7), occlusive (n = 4), and normal (n = 3) aorta. RESULTS: Tissue MMP-2 mRNA levels were significantly greater in aneurysmal aorta (1.032 +/- 0.164, n = 5) than in either occlusive (0.553 +/- 0.027, n = 4, p < 0.02) or normal aorta (0.230 +/- 0.038, n = 3, p < 0.002). Differences in TIMP-2 mRNA levels were not significant (aneurysmal aorta 0.207 +/- 0.042, n = 3; occlusive aorta 0.413 +/- 0.164, n = 3; normal aorta 0.260 +/- 0.079, n = 4; p = 0.34), although numbers were small. Cultured aneurysmal and normal VSMCs constitutively expressed both MMP-2 and TIMP-2. In situ studies colocalized tissue MMP-2 and TIMP-2 expression to VSMCs and macrophages surrounding inflammation in aneurysmal adventita, but to atherosclerotic plaque in occlusive aorta. CONCLUSIONS: MMP-2 and TIMP-2 are expressed in aneurysmal, occlusive, and normal aorta. MMP-2 expression is significantly greater in aneurysmal than in either occlusive or normal aorta. Cultured aneurysmal VSMCs constitutively express both MMP-2 and TIMP-2. Differential patterns of expression seen in situ and elevated tissue MMP-2 mRNA levels in aneurysmal versus occlusive aorta suggest that MMP-2 may be responsible for localized plaque remodeling in occlusive disease and for diffuse adventitial collagen and elastin destruction in aneurysms.
Aged↗
Infection of Macaca nemestrina brain with human immunodeficiency virus type 1.
We previously reported that pigtailed macaques (Macaca nemestrina) became infected after intravenous inoculation with the LAI strain of human immunodeficiency virus type 1 (HIV-1), an isolate that replicates in both M. nemestrina lymphocytes and blood-derived monocyte/macrophages. In the current study we investigated the presence of HIV-1 and pathology in the postmortem brains of four of these macaques. Histopathological findings revealed focal lesions in white matter in the frontal and occipital lobes of one macaque, with myelin loss, nerve fibre loss, and gliosis within these lesions. Semi-quantitative, solution-based PCR revealed HIV-1 DNA in the brains of two of the other macaques. Using slide-based PCR-driven in situ hybridization, we studied these two macaques further and detected intranuclear, circular HIV-1 DNA in vascular endothelia and other non-neuronal brain cells. These findings indicate that M. nemestrina brain can be infected with HIV-1 in vivo and may provide a useful animal model for understanding early HIV-1 brain infection in humans.
AIDS Dementia Complex↗
Detection of CD4+ T cells harboring human immunodeficiency virus type 1 DNA by flow cytometry using simultaneous immunophenotyping and PCR-driven in situ hybridization: evidence of epitope masking of the CD4 cell surface molecule in vivo.
Human immunodeficiency virus type 1 (HIV-1) infection of T cells and cells of the monocyte/macrophage lineage requires a specific interaction between the CD4 antigen expressed on the cell surface and the HIV-1 external envelope glycoprotein (gp120). To study the association between HIV-1 infection and modulation of cell surface expression of the CD4 molecule in vivo, we examined the CD4+ T cells harboring proviral DNA obtained from HIV-1-infected individuals who had received no antiretroviral therapy for at least 90 days. Simultaneous immunophenotyping of CD4 cell surface expression and PCR-driven in situ hybridization for HIV-1 DNA were used to resolve the CD4+ T cells into distinct populations predicted upon the presence or absence of proviral DNA. Among the HIV-1-infected study subjects, the percentage of CD4+ T cells harboring proviral DNA ranged from 17.3 to 55.5%, with a mean of 40.5%. Cell surface fluorescent staining with anti-CD4 antibody directed against a non-gp120 binding site-related epitope (L120) or a conformation-dependent epitope of the gp120 binding site (Leu 3A) demonstrated either an equivalent or a 1.5- to 3-fold-lower cell surface staining intensity for the HIV-1 DNA-positive subpopulation relative to the HIV-1 DNA-negative subpopulation, respectively. These data suggest that masking or alteration of specific epitopes on the CD4 molecule occurs after viral infection.
CD4 Antigens↗
In situ localization and quantification of mRNA for 92-kD type IV collagenase and its inhibitor in aneurysmal, occlusive, and normal aorta.
Ninety-two-kilodalton type IV collagenase (MMP-9) is present in aortic aneurysms and may be important to the pathogenesis of this disease. Alteration in expression of MMP-9 or its inhibitor, the tissue inhibitor of metalloproteinase type 1 (TIMP-1), could increase degradation of extracellular matrix and lead to aneurysm formation. The purpose of this study was (1) to measure tissue levels of MMP-9 and TIMP-1 mRNA in aneurysmal (AAA), atherosclerotic occlusive (AOD), and normal (NL) human infrarenal aorta; (2) to test for their expression by cultured AAA and NL vascular smooth muscle cells (VSMCs); and (3) to locate in situ the cells responsible for mRNA production within AAA, AOD, and NL aortic wall. Total RNA extracted from AAA (n = 8), AOD (n = 8), and NL (n = 7) tissue was subjected to Northern analysis. Signals for MMP-9 and TIMP-1 were normalized to alpha-tubulin. Mean values +/- SEM were compared by ANOVA. NL and AAA VSMCs were cultured, passaged, and grown to confluence before RNA extraction and Northern analysis. In situ hybridization with digoxigenin-labeled RNA probes localized cells responsible for MMP-9 and TIMP-1 mRNA expression within sections of AAA (n = 5), AOD (n = 2), and NL (n = 2) aorta. MMP-9 mRNA levels were significantly greater in AAA (0.855 +/- 0.180) than NL (0.046 +/- 0.23) (P < .02), but differences between AOD (0.406 +/- 0.196) and AAA or AOD and NL were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Aneurysm↗