Biomedical subjects

Stephen P Brooks

Publications and source records attributed to Stephen P Brooks.

9 recordsLinked to original sources

PubMed2006

Optimal reactive vaccination strategies for a foot-and-mouth outbreak in the UK.

Foot-and-mouth disease (FMD) in the UK provides an ideal opportunity to explore optimal control measures for an infectious disease. The presence of fine-scale spatio-temporal data for the 2001 epidemic has allowed the development of epidemiological models that are more accurate than those generally created for other epidemics and provide the opportunity to explore a variety of alternative control measures. Vaccination was not used during the 2001 epidemic; however, the recent DEFRA (Department for Environment Food and Rural Affairs) contingency plan details how reactive vaccination would be considered in future. Here, using the data from the 2001 epidemic, we consider the optimal deployment of limited vaccination capacity in a complex heterogeneous environment. We use a model of FMD spread to investigate the optimal deployment of reactive ring vaccination of cattle constrained by logistical resources. The predicted optimal ring size is highly dependent upon logistical constraints but is more robust to epidemiological parameters. Other ways of targeting reactive vaccination can significantly reduce the epidemic size; in particular, ignoring the order in which infections are reported and vaccinating those farms closest to any previously reported case can substantially reduce the epidemic. This strategy has the advantage that it rapidly targets new foci of infection and that determining an optimal ring size is unnecessary.

Animals↗

PubMed2006

Topographic determinants of foot and mouth disease transmission in the UK 2001 epidemic.

BACKGROUND: A key challenge for modelling infectious disease dynamics is to understand the spatial spread of infection in real landscapes. This ideally requires a parallel record of spatial epidemic spread and a detailed map of susceptible host density along with relevant transport links and geographical features. RESULTS: Here we analyse the most detailed such data to date arising from the UK 2001 foot and mouth epidemic. We show that Euclidean distance between infectious and susceptible premises is a better predictor of transmission risk than shortest and quickest routes via road, except where major geographical features intervene. CONCLUSION: Thus, a simple spatial transmission kernel based on Euclidean distance suffices in most regions, probably reflecting the multiplicity of transmission routes during the epidemic.

Animals↗

PubMed2006

Manual exfoliation plus immunomagnetic bead separation as an initial step toward translational research.

CONTEXT: The development of biotechnologic platforms capable of high throughput analysis has ushered in a promising new era of translational medicine. However, most studies to date are based on in vitro cell lines or substitute models for human disease. Although these model systems have proven insightful, it is readily becoming apparent that human clinical tissue must be studied in order to fully understand all the nuances of human disease. Studies that are based on human tissue, however, are limited by qualitative and quantitative issues, factors often precluding their use in high throughput studies. OBJECTIVE: To develop a simple and rapid tissue procurement protocol for use in obtaining a homogeneous epithelial cell population from clinical tissue and the recovery of nucleic acids and proteins of high quality and quantity. Also, to determine if the technique preserves tissue, thereby allowing morphologic correlation with molecular findings. DESIGN: Performance of manual exfoliation to procure cells from clinical resection specimens and use of immunomagnetic beads embedded with the antibody ber-Ep4 for the positive enrichment of a homogeneous epithelial cell population. Nucleic acids and proteins are then separated using a phenol plus guanidine thiocyante solution. Nucleic acids and proteins are quantitated and qualitatively analyzed using standard laboratory techniques. RESULTS: Nucleic acids and proteins of high quality and quantity were recovered following manual exfoliation and immunomagnetic bead separation. Tissue architecture was not destroyed, thus permitting histologic and molecular correlation. CONCLUSIONS: A simple and reproducible protocol is presented that may enable the molecular profiling of clinically resected tissue. Although the technique is currently limited to certain tissue and tumor types, further research will broaden its overall application.

Adenocarcinoma↗

PubMed2005

IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells.

Memory T cells in human non-small cell lung cancer are unresponsive to progressing tumors. T cells were evaluated at the single cell level by imaging the nuclear translocation of NF-kappaB and NFAT via immunofluorescence confocal microscopy as an early measure of responsiveness to T cell receptor triggering. Little translocation of NF-kappaB or NFAT occurred in tumor-associated T cells in response to CD3+CD28 cross-linking under conditions which led to maximal translocation in normal donor peripheral blood T cells. TNF-alpha induced maximal NF-kappaB translocation in these T cells, indicating that they remain receptive to alternative signaling pathways, and pulsing with IL-12 prior to TCR triggering reversed their apparent anergy. T cells from additional chronic inflammatory microenvironments demonstrated a similar refractoriness to TCR activation, suggesting either that a common regulatory mechanism present within the microenvironment controls these cells or that with continuous antigen exposure, they remain refractory to activation via the TCR.

Active Transport, Cell Nucleus↗

PubMed2004

Using conservation of pattern to estimate spatial parameters from a single snapshot.

Rapid reaction in the face of an epidemic is a key element in effective and efficient control; this is especially important when the disease has severe public health or economic consequences. Determining an appropriate level of response requires rapid estimation of the rate of spread of infection from limited disease distribution data. Generally, the techniques used to estimate such spatial parameters require detailed spatial data at multiple time points; such data are often time-consuming and expensive to collect. Here we present an alternative approach that is computationally efficient and only requires spatial data from a single time point, hence saving valuable time at the start of the epidemic. By assuming that fundamental spatial statistics are near equilibrium, parameters can be estimated by minimizing the expected rate of change of these statistics, hence conserving the general spatial pattern. Although applicable to both ecological and epidemiological data, here we focus on disease data from computer simulations and real epidemics to show that this method produces reliable results that could be used in practical situations.

Animals↗

PubMed2003

Bayesian computation: a statistical revolution.

The 1990s saw a statistical revolution sparked predominantly by the phenomenal advances in computing technology from the early 1980s onwards. These advances enabled the development of powerful new computational tools, which reignited interest in a philosophy of statistics that had lain almost dormant since the turn of the century. In this paper we briefly review the historic and philosophical foundations of the two schools of statistical thought, before examining the implications of the reascendance of the Bayesian paradigm for both current and future statistical practice.

Journal Article↗

PubMed2003

Intra-tumoral injection of CpG results in the inhibition of tumor growth in murine Colon-26 and B-16 tumors.

Direct tumor injections of CpG (ODN #1826) into murine tumors markedly suppressed the tumor growth and increased the survival of the mice. Tumor growth was reduced by 60-67% in Colon Tumor 26 (CT-26) and B-16 melanoma tumors treated with CpG as compared to untreated one. In CT-26 and B-16 tumors treated with CpG, the average survival of the animals were prolonged to 26 and 28 d as compared to 16 and 18 d in control respectively. Long-term surviving animals in CT-26 tumor groups were also protected from a subsequent injection of a lethal dose of tumor cells. In the present study, effect of CpG was mediated through CD8+ T cells, as their depletion resulted in the abrogation of the therapeutic effects of the CpG. It suggests that direct tumor injection might be a simple means of achieving a clinical response in cancer patients.

Animals↗

PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores allostimulatory function to accessory cells in patients with AIDS.

BACKGROUND: Impaired allostimulatory function of dendritic cells in patients with AIDS has been reported previously. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can restore the T-cell stimulatory function in transforming growth factor-beta 1 (TGF-beta 1)-inhibited murine accessory cells. We now report the effect of intravenous recombinant human GM-CSF (rhGM-CSF) on accessory cells of HIV-infected patients. METHOD: The in vivo effect of GM-CSF on allostimulatory function of accessory cells was evaluated. Seventeen individuals with AIDS received a single infusion of rhGM-CSF (125 mg/m(2) over 120 minutes). Samples of peripheral blood lymphocytes (PBL) were taken at 1, 5, and 24 hours after infusion, and the allostimulatory capacity was measured. RESULTS: A single bolus infusion of rhGM-CSF resulted in significantly increased accessory cell function in 13/17 (88%) patients at one or more assayed time points after infusion. CONCLUSION: These results suggest that the administration of rhGM-CSF can potentially restore allostimulatory function to accessory cells in HIV-infected patients, and this presents a novel way of immune reconstitution. Clinical significance of this approach of immune reconstitution in AIDS patients warrants further investigations.

AIDS Dementia Complex↗

PubMedDate not supplied

Cytokines and chemokines are expressed at different levels in small and large murine colon-26 tumors following intratumoral injections of CpG ODN.

Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small tumors resulted in tumor necrosis and extensive inflammatory cell infiltration, with average survival that is significantly higher (48.1 +/- 34 days) when compared to control ODN-treated mice (16.1 +/- 3.5 days). Cytokines and chemokines are expressed at different levels in small and large CT-26 tumors following intratumoral injections of CpG ODN. We observed that granulocyte-macrophage colony-stimulating factor and interleukin (IL) 6 are the major cytokines that were overexpressed in CpG ODN-treated small tumors but not in large tumors. Similarly, several chemokines (CXCL1, CCL2, and CCL3) were also significantly higher in CpG ODN-treated small tumors compared to control ODN-treated tumors.

Adjuvants, Immunologic↗