Our findings suggest that HIV+ patients on highly active antiretroviral therapy can undergo successful renal transplantation with a low incidence of both AR and AIDS-associated and non-AIDS associated infections, despite associated risk factors for poorer outcome. Our encouraging but preliminary results with this protocol will need to be verified in larger numbers of HIV+ renal allograft recipients with longer follow-up.
Activation of matrix metalloproteinases (MMPs) in the heart is known to facilitate cardiac remodeling and progression to failure. We hypothesized that regional dyskinetic wall motion of the left ventricle would stimulate activation of MMPs. Abnormal wall motion at a target site on the anterior lateral wall of the left ventricle was induced by pacing atrial and ventricular sites of five open-chest anesthetized dogs. Changes in shortening at the left ventricular (LV) pacing site and at a remote site at the anterior base of the left ventricle were monitored with piezoelectric crystals. Simultaneous atrial and ventricular pacing resulted in abnormal motion at the LV pacing site, yielding early shortening and late systolic lengthening, whereas the shortening pattern at the remote site remained unaffected. Assessment of global myocardial MMP activity showed a sevenfold increase in substrate cleavage (P < 0.02) at the LV pacing site relative to the remote site. Gelatin zymography revealed increases in 92-kDa MMP-9 activity and 86-kDa MMP-9 activity at the LV pacing site relative to the remote site, whereas MMP-2 activity was unaffected. Abnormal wall motion was associated with increases in collagen degradation (approximately 2-fold; P < 0.03), plasmin activity (approximately 1.5-fold; P < 0.05), nitrotyrosine levels (approximately 20-fold; P = 0.05), and inflammatory infiltrate (approximately 2-fold; P < 0.02) relative to the remote site. Results indicate that regional dyskinesis induced by epicardial activation is sufficient to stimulate significant MMP activity in the heart, suggesting that abnormal wall motion is a stimulus for MMP activation.
Acute rejection (AR) remains problematic in renal transplantation. As a marker, serum creatinine is limited, warranting a more effective screening tool. Raman spectroscopy (RS) can detect T-cell activation with high sensitivity. In this study we explore its specificity. Seventy-five inactivated, 40 alloantigen-activated, and 75 CD3/ CD28-activated T cells were analyzed using RS. CD3/CD28-activated peak magnitudes (PM) were 4.3% to 23.9% lower than inactivated PM at positions: 903, 1031, 1069, 1093, 1155, 1326, and 1449 cm 21 , with a difference in peak ratio (PR) observed at the 1182:1195 cm 21 position (0.91 AE 0.06 vs. 1.2 AE 0.01, respectively: P 5 0.006). Differences in CD3/CD28-and alloantigen-activated PM were observed at: 903, 1031, 1093, 1155, 1326, and 1449 cm 21 , with no PR differences at the 1182:1195 cm 21 position (0.91 6 0.06 vs. 0.86 6 0.09: P 5 0.8). Spectral signature separation of CD3/CD28-and alloantigen-activated groups was 100% specific and sensitive. We conclude that RS can differentiate T cells activated by different stimuli with high sensitivity and specificity. '
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