Showing papers by "John C. S. Harding published in 2009"

Bioluminescence imaging of myeloperoxidase activity in vivo.

Abstract: The myeloperoxidase (MPO) system of activated phagocytes is central to normal host defense mechanisms, and dysregulated MPO contributes to the pathogenesis of inflammatory disease states ranging from atherosclerosis to cancer. Here we show that upon systemic administration, the small molecule luminol enables noninvasive bioluminescence imaging (BLI) of MPO activity in vivo. Luminol-BLI allowed quantitative longitudinal monitoring of MPO activity in animal models of acute dermatitis, mixed allergic contact hypersensitivity, focal arthritis and spontaneous large granular lymphocytic tumors. Bioluminescence colocalized with histological sites of inflammation and was totally abolished in gene-deleted Mpo(-/-) mice, despite massive tissue infiltration of neutrophils and activated eosinophils, indicating that eosinophil peroxidase did not contribute to luminol-BLI in vivo. Thus, luminol-BLI provides a noninvasive, specific and highly sensitive optical readout of phagocyte-mediated MPO activity in vivo and may enable new diagnostic applications in a wide range of acute and chronic inflammatory conditions.

T-cell activation promotes tumorigenesis in inflammation-associated cancer

Abstract: Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR) transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

Ring tests to evaluate the performance of Porcine circovirus-2 (PCV-2) polymerase chain reaction (PCR) assays used in North American diagnostic laboratories.

Abstract: Two laboratory studies involving 11 laboratories were undertaken to assess the performance of North American Porcine circovirus-2 (PCV-2) polymerase chain reaction (PCR) assays. Laboratories received identical submissions containing randomly coded positive and negative control samples, and serially diluted PCV-2-spiked samples. In study 1 and 2, respectively, spiked samples contained measured amounts of PCV-2 virus or DNA. All but 1 assay detected DNA in the most concentrated spiked sample. There were no statistical differences in the proportion of positive or negative samples reported by quantitative (n = 7) versus non-quantitative (n = 6) assays. Across both studies, the false positive rate was 17% (4 out of 23), and 17% (2 out of 12) of assays cross-reacted with PCV-1. The most sensitive assay detected PCV-2 DNA levels about 100 000 times lower the least sensitive assay. This study demonstrated that the PCR assays available in North American diagnostic labs vary considerably in their detection limits and quantification.

Parturition induction two days prior to term decreases birth weight and lactational growth, but not piglet maturity, health or post-weaning growth

Abstract: Premature parturition induction may adversely affect postnatal health and performance. The objective of this study was to evaluate the impact of cloprostenol induction 2 d prior to term on piglet maturity (liver glycogen), postnatal productivity (birth weight, growth rate), and health (morbidity, mortality, passive antibody, fecal Clostridium perfringens). Two hundred and sixteen pregnant sows and their progeny (2827 piglets) were assigned to the study. Induction decreased gestation length 2.1 d (P < 0.0001), birth weight 107.2 g pig-1 (P = 0.0004), lactational growth 10.1 g d-1 (P = 0.05), and day 16 weight 0.30 kg pig-1 (P < 0.05). Liver glycogen concentration was 71.2 µg g-1 higher in the stillborns of induced sows (P = 0.03), suggesting the pre-term sows were catabolic. No group differences in post-weaning growth rate, pre-weaning mortality or morbidity, passive antibody transfer or fecal Clostridium perfringens level were found. Reduced lactational growth appeared attributable to the reductions in ge...