Biomedical subjects

R Vessey

Publications and source records attributed to R Vessey.

4 recordsLinked to original sources

PubMed2006

Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects.

AIMS: Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects. METHODS: Single doses of tiotropium bromide (Tio) 54 and 18 mcg, ipratropium bromide (IB) 40 mcg and placebo were administered. Specific conductance (sGaw), total lung capacity (TLC), inspiratory capacity (IC) and residual volume (RV) were measured using plethysmography, while IOS measured resistance (R5-25) and reactance (RF and X5). Pulmonary function was measured for 26 h post dose. RESULTS: Tio caused significant improvements in sGaw, forced expiratory voume in 1 s (FEV(1)), maximum mid-expiratory flow (MMEF) and R5-R25 at time points up to 26 h, with no clear differences between doses. IB improved the same parameters, but only up to 8 h. The weighted mean change (0-24 h) caused by Tio 54 mcg compared with placebo for FEV(1) was 240 ml (95% confidence interval 180, 300), while for sGaw the ratio of geometric means (Tio compared with placebo) was 1.35 (1.28, 1.41). Neither drug caused consistent statistically significant changes in RF, forced vital capacity, TLC or IC over 26 h. RV was significantly improved from 8 to 24 h by Tio 54 mcg only. CONCLUSIONS: In addition to spirometry, IOS resistance measurements and sGaw can distinguish between the effects of long- and shortacting anticholinergic effects in healthy subjects.

Adult↗

PubMed2000

Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine.

A DNA vaccine against the hepatitis B virus (HBV) was evaluated for safety and induction of immune responses in 12 healthy, hepatitis-naïve human volunteers using the needle-free PowderJect system to deliver gold particles coated with DNA directly into cells of the skin. Three groups of four volunteers received three administrations of DNA encoding the surface antigen of HBV at one of the three dose levels (1, 2, or 4 microg). The vaccine was safe and well tolerated, causing only transient and mild to moderate responses at the site of administration. HBV-specific antibody and both CD4+ and CD8+ T cell responses were measured before and after each immunization. All the volunteers developed protective antibody responses of at least 10 mIU/ml. In volunteers who were positive for the HLA class I A2 allele, the vaccine also induced antigen-specific CD8+ T cells that bound HLA-A2/HBsAg(335-343) tetramers, secreted IFN-gamma, and lysed target cells presenting a hepatitis B surface antigen (HBsAg) CTL epitope. Enumeration of HBsAg-specific T cells producing cytokine indicated preferential induction of a Type 1 T helper cell response. These results provide the first demonstration of a DNA vaccine inducing protective antibody titers and both humoral and cell-mediated immune responses in humans.

Adult↗

PubMed2000

Functionally distinct CD8+ memory T cell subsets in persistent EBV infection are differentiated by migratory receptor expression.

Human memory T lymphocytes have recently been re-defined as central or effector memory cells (Sallusto, F., Lenig, D., Forster, R., Lipp, M. and Lanzavecchia, A., Nature 1999. 401: 708-712). Effector memory cells (T(em)) are targeted to the peripheral tissues and show rapid effector function in response to antigenic stimulation. Central memory (T(cm)) cells are targeted to the lymph nodes and cannot be immediately activated. In this report HLA-A2-Epstein-Barr virus (EBV) peptide tetramers have been used to characterize the EBV-specific CD8+ T cell subsets in persistent EBV infection. In short-term activation studies two populations of tetramer-positive T cells were identified. One group resembled T(em) cells in that they rapidly produced IFN-gamma and lacked the lymph node homing receptor, CD62L, the second was similar to T(cm) cells since they were CD62L+ but could not be immediately induced to express IFN-gamma.

Antigens, CD↗

PubMed2000

Tolerability and immune responses in humans to a PowderJect DNA vaccine for hepatitis B.

We are developing a DNA vaccine toward hepatitis-B virus (HBV) using PowderJect's proprietary needle-free technology to deliver DNA-coated gold particles directly into cells of the skin. Preclinical studies in animals showed that (i) microgram doses of the DNA vaccine were sufficient to immunize pigs and non-human primates to antibody levels comparable to those obtained with a commercial recombinant subunit vaccine; (ii) the DNA vaccine was effective in mouse strains that respond poorly to protein subunit vaccines; (iii) the vaccine induces robust cytotoxic T-cell responses, and (iv) the vaccine is non-toxic and well tolerated. Based on these findings, this DNA vaccine was evaluated for safety, tolerability, and the induction of immune responses in phase 1 clinical studies in healthy, hepatitis-naïve human volunteers. Preliminary results indicate that the vaccine is safe and well tolerated, and elicits both humoral and cellular immune responses in man.

Animals↗