Response of balloon-expandable endoprosthetic metallic stents subjected to over-expansion in vitro.

We attempted to evaluate the in vitro behavior and performance of balloon-expandable endoprosthetic metallic stents subjected to over-expansion (OE). Seventy-two balloon-expandable endoprosthetic stents, representing 22 models from six manufacturers, were overexpanded in vitro. Stents were initially expanded to their maximum manufacturer- recommended diameter and then over-expanded incrementally to their endpoints. Endpoints for OE were either stent disarticulation or an inability to undergo further expansion despite balloon insufflation to maximum burst pressure. Measurements of stent dimensions were recorded at each overexpanded diameter and comparisons were made to manufacturer's specifications. A total of 288 balloon-driven expansions were performed on 72 stents. Sixteen stents were expanded to large diameters (> or = 16 mm), 20 stents underwent OE of 50% or greater. One model tended to disarticulate after OE greater than 50%. There were five models that had a tendency to disarticulate after minimal OE. Five models were resistant to OE (25% or less OE) but did not disarticulate. Nearly all stents showed some degree of foreshortening with OE, while 36 stents underwent foreshortening of 30% or more. Models that are not recommended for OE include Intrastent, Intrastent DoubleStrut, NIR Royale and Omniflex. Good candidates for OE include Intrastent DoubleStrut LD, Palmaz large, Medtronic Extra Support Biliary Plus and Medtronic Flexible Biliary. Palmaz XL remains the only model available for expansion from 20 to 28 mm in diameter. For the remaining stents, OE is possible, however, caution should be used.

High frequency of cytomegalovirus-specific cytotoxic T-effector cells in HLA-A*0201-positive subjects during multiple viral coinfections.

How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-specific CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-specific CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strengths.

Simian immunodeficiency virus-specific cytotoxic T lymphocytes and protection against challenge in rhesus macaques immunized with a live attenuated simian immunodeficiency virus vaccine.

In this study, we examined the role of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes (CTLs) in macaques immunized with an attenuated strain of simian immunodeficiency virus (SIVmac239Deltanef) in protection against pathogenic challenge with SIVmac251. Our results indicate that attenuated SIVmac239Deltanef can elicit specific CTL precursor cells (CTLp), but no correlation was observed between breadth or strength of CTLp response to structural proteins SIV-Env, -Gamg or -Pol (as measured by limiting dilution assay) and protection against infection. In one animal, we longitudinally followed the SIV-Gag-specific response to an MHC class I Mamu-A*01-restricted epitope p11C, C-M using a tetrameric MHC/peptide complex reagent. A low frequency of SIV p11C, C-M peptide-specific tetramer-reactive cells was present at the time of challenge but could be expanded in vitro. Surprisingly, the low level of Mamu-A*01/p11C, C-M-specific CTLs induced through attenuated SIVmac239Deltanef vaccination increased in the absence of detectable SIVmac251 or SIVmac239Deltanef proviral DNA. Overall, our results suggest that protection against infection in this model can be achieved through more than one mechanism, with SIV-specific CTLs being important in controlling SIVmac239Deltanef viral replication postchallenge.

HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy.

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1-infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than 500 copies/mL in 2 subjects for more than 12 and more than 24 months, respectively, and in 1 subject for 4 months on 1 occasion. Three subjects failed to contain plasma viremia. Broad and strong HIV-1-specific immune responses were detected in subjects with prolonged suppression of viral replication. This longitudinal study suggests that containment of HIV-1 replication to low or undetectable levels after discontinuation of HAART is associated with strong virus-specific immune responses. Boosting of HIV-1-specific immune responses should be considered as an adjunctive treatment strategy for HIV-1-infected individuals on HAART.

Comparison of restimulation methods to elicit SIV specific cytotoxic T-lymphocytes (CTL) in vitro: Staphylococcal enterotoxin B (SEB) provides a novel method for the quantification of SIV specific CTL precursors.

Most investigators believe that an effective HIV-1 vaccine will have to induce high levels of HIV-1 specific cytotoxic T-cells (CTL). The macaque SIV challenge/protection model system has been used to test candidate vaccines, but quantitative immunogenicity measurements are difficult due to technical limitations of the assays available. The quantification of SIV specific CTLp is crucial to understanding correlates of immunity for these vaccines, but are difficult to measure. We have compared various methods to quantify SIV specific CTLp, and describe a novel method of SIV specific CTL in vitro stimulation using the superantigen Staphylococcal enterotoxin B (SEB). SEB can stimulate high levels of CTLp in vitro, and provides an alternative method to induce SIV specific CTL.