The persistence of HIV-1 in virally suppressed infected individuals on highly active antiretroviral therapy (HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additional therapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2 has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancing HIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) in CD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4 + T lymphocytes from HIV-1-infected patients on suppressive HAART. Moreover, the phylogenetic analyses of viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had been activated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstrate that different activators of proviral latency may perturb and potentially deplete only selected, specific portions of the proviral archive in virally suppressed individuals. The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4 + T lymphocytes, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immuneantiretroviral approaches.
The persistence of HIV-1 in virally suppressed infected individuals on highly active antiretroviral therapy (HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additional therapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2 has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancing HIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) in CD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4 + T lymphocytes from HIV-1-infected patients on suppressive HAART. Moreover, the phylogenetic analyses of viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had been activated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstrate that different activators of proviral latency may perturb and potentially deplete only selected, specific portions of the proviral archive in virally suppressed individuals. The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4 + T lymphocytes, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immuneantiretroviral approaches.
The novel antitumor-promoting phorbol ester, prostratin, was evaluated for its ability to induce the expression of latent, highly active antiretroviral therapy (HAART)-persistent human immunodeficiency virus type I (HIV-1) from specific subsets of patients' peripheral blood cells. This evaluation was performed relative to the use of other cellular activating agents, such as OKT3, a monoclonal antibody against the human T cell receptor, interleukin-2 (IL-2), phytohemagglutinin (PHA), p24 antigen (HIV-1-specific capsid protein), and a molecular relative of prostratin, 12-deoxyphorbol 13-phenylacetate (DPP). Prostratin performed as efficiently as the other cellular activators at inducing the expression of latent HIV-1 from cells of patients on virally suppressive HAART. Of interest was the induction of a novel species of latent virus from the cells of an individual after exposure to the HIV-1-specific capsid protein, p24, relative to virus expression induced by several other cell activators. This suggests that a variety of agents may be available for animal model studies of lentiviral latency and clinical use to broadly induce the expression of latent, HAART-persistent HIV-1 in vivo with the goal of potential HIV-1 reservoir depletion or eradication.
Background: There is growing enthusiasm for robotic and transanal surgery as an alternative to open or laparoscopic surgery for colorectal cancer (CRC). We examined the impact of surgical modality on body image and quality of life (QOL) in patients receiving anterior resection for CRC. Methods: We used a mixed-methods approach, consisting of a chart review and semistructured interviews with CRC patients, at least 8 months after surgery. We assessed cosmetic outcomes and QOL using validated questionnaires. Results: Thirty patients were stratified into open (n = 8), laparoscopic (n = 12) and robotic (n = 10) groups. Mean body image scores were significantly higher (i.e., poorer body image) in patients receiving open surgery (mean difference [MD] +5.7 with laparoscopy, p < 0.001). Open surgery was more detrimental to physical function, including strenuous activities, prolonged ambulation and self-care (MD-11.6 with laparoscopy, p = 0.039). Patients receiving laparoscopic surgery reported superior role (MD +27.6 with open surgery, p = 0.002) and social function (MD +13.7 with open surgery, p = 0.042), including the ability to enjoy hobbies, family life and social activities. Surgical modality did not affect emotional and cognitive function or symptoms including genitourinary function, pain and defecation. Conclusion: The negative impact of open surgery on body image and physical function warrants further educational interventions for patients. The protective effect of laparoscopy on role and function may be associated with "tumour factors" that are unaccounted for in the European Organization for Research and Treatment of Cancer questionnaires. Open surgery is detrimental to body image and physical function in patients receiving anterior resection for CRC. Prospective randomized studies are required to validate these findings. Contexte : On observe un intérêt croissant pour la chirurgie transanale robotique comme solution de rechange à la chirurgie ouverte ou laparoscopique dans les cas de cancer colorectal (CCR). Nous avons analysé l'impact de la modalité chirurgicale sur l'image corporelle et la qualité de vie (QdV) chez les patients ayant subi une résection antérieure pour CCR. Méthodes : Nous avons utilisé une approche à méthodologie mixte, composée d'une revue des dossiers et d'entrevues semi-structurées avec des patients atteints de CCR, au moins 8 mois après la chirurgie. Nous avons évalué les résultats cosmétiques et la QdV au moyen de questionnaires validés. Résultats : Trente patients ont été stratifiés en 3 groupes : chirurgie ouverte (n = 8), laparoscopique (n = 12) et robotique (n = 10). Les scores moyens pour l'image corporelle ont été significativement plus élevés (c.-à-d., image corporelle plus négative) chez les patients ayant subi une chirurgie ouverte (différence moyenne [DM] +5,7 avec la laparoscopie, p < 0,001). La chirurgie ouverte a été plus nuisible au fonctionnement physique, y compris aux activités exigeantes, à la déambulation prolongée et à l'autosoin (DM-11,6 avec la laparoscopie, p = 0,0...
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