Comparison of Colour Duplex Ultrasound with Computed Tomography to Measure the Maximum Abdominal Aortic Aneurysmal Diameter

Maximum diameter of an abdominal aortic aneurysm (AAA) is themain indication for surgery. This study compared colour duplex ultrasound (CDU) and computed tomography (CT) in assessing AAA diameter. Patients andMethods. Patients were included if they had both scans performed within 90 days. Pearson’s correlation coefficient, paired t-test, and limits of agreement (LOA) were calculated for the whole group. Subgroup analysis of small (6.5 cm) aneurysms was performed. A P value o

Adipose tissue is enriched for activated and Late-differentiated CD8+ T cells, and shows distinct CD8+ receptor usage, compared to blood in HIV-infected persons

BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell populations in adipose tissue among persons on long-term antiretroviral therapy and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue. RESULTS: Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05). CONCLUSIONS: Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons

Cytomegalovirus (CMV) Epitope–Specific CD4 + T Cells Are Inflated in HIV + CMV + Subjects

Select CMV epitopes drive life-long CD8+ T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4+ T cells specific for human CMV (HCMV) are elevated in HIV+ HCMV+ subjects. To determine whether HCMV epitope–specific CD4+ T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4+ T cells in coinfected HLA-DR7+ long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4+ T cells were inflated among these HIV+ subjects compared with those from an HIV− HCMV+ HLA-DR7+ cohort or with HLA-DR7–restricted CD4+ T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4+ T cells consisted of effector memory or effector memory–RA+ subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell–transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX3CR1, CD38, or HLA-DR but less often coexpressed CD38+ and HLA-DR+. The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4+ T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease

Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library

The peroxisome proliferator-activated receptors (PPARs) were cloned as orphan members of the nuclear receptor superfamily of transcription factors. The identification of subtype-selective ligands for PPARα and PPARγ has led to the discovery of their roles in the regulation of lipid metab. and glucose homeostasis. No subtype-selective PPARδ ligands are available and the function of this subtype is currently unknown. A three-component library was designed in which one of the monomers was biased towards the PPARs and the other two monomers were chosen to add chem. diversity. Synthesis and screening of the library resulted in the identification of pools with activity on each of the PPAR subtypes. Deconvolution of the pools with the highest activity on PPARδ led to the identification of GW 2433 as the first high-affinity PPARδ ligand. [3H]GW 2433 is an effective radioligand for use in PPARδ competition-binding assays. Conclusions: The synthesis of biased chem. libraries is an efficient approach to the identification of lead mols. for members of sequence-related receptor families. This approach is well suited to the discovery of small-mol. ligands for orphan receptors