1,292 research outputs found

    Envelope Determinants of Equine Lentiviral Vaccine Protection

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    Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

    Investigation into pedestrian exposure to near-vehicle exhaust emissions

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    <p>Abstract</p> <p>Background</p> <p>Inhalation of diesel particulate matter (DPM) is known to have a negative impact on human health. Consequently, there are regulations and standards that limit the maximum concentrations to which persons may be exposed and the maximum concentrations allowed in the ambient air. However, these standards consider steady exposure over large spatial and time scales. Due to the nature of many vehicle exhaust systems, pedestrians in close proximity to a vehicle's tailpipe may experience events where diesel particulate matter concentrations are high enough to cause acute health effects for brief periods of time.</p> <p>Methods</p> <p>In order to quantify these exposure events, instruments which measure specific exhaust constituent concentrations were placed near a roadway and connected to the mouth of a mannequin used as a pedestrian surrogate. By measuring concentrations at the mannequin's mouth during drive-by events with a late model diesel truck, a representative estimate of the exhaust constituent concentrations to which a pedestrian may be exposed was obtained. Typical breathing rates were then multiplied by the measured concentrations to determine the mass of pollutant inhaled.</p> <p>Results</p> <p>The average concentration of diesel particulate matter measured over the duration of a single drive-by test often exceeded the low concentrations used in human clinical studies which are known to cause acute health effects. It was also observed that higher concentrations of diesel particulate matter were measured at the height of a stroller than were measured at the mouth of a mannequin.</p> <p>Conclusion</p> <p>Diesel particulate matter concentrations during drive-by incidents easily reach or exceed the low concentrations that can cause acute health effects for brief periods of time. For the case of a particularly well-tuned late-model year vehicle, the mass of particulate matter inhaled during a drive-by incident is small compared to the mass inhaled daily at ambient conditions. On a per breath basis, however, the mass of particulate matter inhaled is large compared to the mass inhaled at ambient conditions. Finally, it was determined that children, infants, or people breathing at heights similar to that of a passing vehicle's tailpipe may be exposed to higher concentrations of particulate matter than those breathing at higher locations, such as adults standing up.</p

    Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study

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    We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50–69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89–1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers

    The effects of walking speed on minimum toe clearance and on the temporal relationship between minimum clearance and peak swing-foot velocity in unilateral trans-tibial amputees

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    yesBackground: Minimum toe clearance is a critical gait event because it coincides with peak forward velocity of the swing foot, and thus, there is an increased risk of tripping and falling. Trans-tibial amputees have increased risk of tripping compared to able-bodied individuals. Assessment of toe clearance during gait is thus clinically relevant. In able-bodied gait, minimum toe clearance increases with faster walking speeds, and it is widely reported that there is synchronicity between when peak swing-foot velocity and minimum toe clearance occur. There are no such studies involving lower-limb amputees. Objectives: To determine the effects of walking speed on minimum toe clearance and on the temporal relationship between clearance and peak swing-foot velocity in unilateral trans-tibial amputees. Study design: Cross-sectional. Methods: A total of 10 trans-tibial participants walked at slow, customary and fast speeds. Minimum toe clearance and the timings of minimum toe clearance and peak swing-foot velocity were determined and compared between intact and prosthetic sides. Results: Minimum toe clearance was reduced on the prosthetic side and, unlike on the intact side, did not increase with walking speed increase. Peak swing-foot velocity consistently occurred (~0.014 s) after point of minimum toe clearance on both limbs across all walking speeds, but there was no significant difference in the toe–ground clearance between the two events. Conclusion: The absence of speed related increases in minimum toe clearance on the prosthetic side suggests that speed related modulation of toe clearance for an intact limb typically occurs at the swing-limb ankle. The temporal consistency between peak foot velocity and minimum toe clearance on each limb suggests that swing-phase inter-segmental coordination is unaffected by trans-tibial amputation. Clinical relevance The lack of increase in minimum toe clearance on the prosthetic side at higher walking speeds may potentially increase risk of tripping. Findings indicate that determining the instant of peak swing-foot velocity will also consistently identify when/where minimum toe clearance occurs

    Astragalus Polysaccharides Attenuate Postburn Sepsis via Inhibiting Negative Immunoregulation of CD4+CD25high T Cells

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    BACKGROUND: Astragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. However, it is not yet clear whether APS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of APS on the immune function of peripheral blood Tregs in postburn sepsis. METHODOLOGY/PRINCIPAL FINDINGS: BALB/C mice were randomly divided into six groups as follows: sham burn group, burn control (burn without infection animals) group, burn plus P. aeruginosa group, burn plus P. aeruginosa with APS (50 mg/kg) treatment group, burn plus P. aeruginosa with APS (100 mg/kg) treatment group, and burn plus P. aeruginosa with APS (200 mg/kg) treatment group, and they were sacrificed on postburn day 1, 3, 5, and 7, respectively, with seven animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4(+) T cells. Phenotypes were analyzed by flow cytometry, and cytokine levels were determined with ELISA. In the burn plus P. aeruginosa group, forkhead/winged helix transcription factor p3 (Foxp3) expression on CD4(+)CD25(+)Tregs were strongly enhanced in comparison to the sham group, and the capacity of CD4(+)CD25(+)Tregs to produce interleukin (IL)-10 was markedly increased. Administration of APS to inhibit CD4(+)CD25(+)Tregs could significantly decrease expression of Foxp3 on CD4(+)CD25(+)Tregs, and IL-10 production in burned mice with P. aeruginosa infection. At the same time, proliferative activity and expression of IL-2 and IL-2Rα on CD4(+) T cells were restored. In contrast, anti-Toll-like receptor 4 (TLR4) antibody could block the effect of APS on Tregs immune function. CONCLUSION: APS might suppress CD4(+)CD25(+)Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1 with activation of CD4(+) T cells in burned mice with P. aeruginosa infection
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