Publications by authors named "P B Christmas"

Objective: To determine the feasibility and short-term efficacy of caregiver-directed constraint-induced movement therapy to improve upper limb function in young children with hemiplegic cerebral palsy.

Design: Randomized controlled trial with masked assessment.

Setting: Community paediatric therapy services.

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CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4). CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay.

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Cytochrome P450 epoxygenases and hydroxylases play a regulatory role in the activation and suppression of inflammation by generating or metabolizing bioactive mediators. CYP2C and CYP2J epoxygenases convert arachidonic acid to anti-inflammatory epoxyeicosatrienoic acids, which have protective effects in a variety of disorders including cardiovascular disease and metabolic syndrome. CYP4A and CYP4F hydroxylases have the ability to metabolize multiple substrates related to the regulation of inflammation and lipid homeostasis, and it is a challenge to determine which substrates are physiologically relevant for each enzyme; the best-characterized activities include generation of 20-hydroxyeicosatetraenoic acid and inactivation of leukotriene B4.

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Article Synopsis
  • The study explores how the body regulates inflammatory responses to prevent tissue damage, focusing on the metabolic process involving leukotriene B4, a pro-inflammatory mediator.
  • Researchers created mouse models to investigate the role of the CYP4F18 enzyme in metabolizing leukotriene B4 by targeting specific genetic regions, confirming that this enzyme is crucial for producing hydroxylated products of leukotriene B4 in neutrophils.
  • Despite the established role of CYP4F18 in leukotriene B4 metabolism, the study finds that its absence does not significantly affect neutrophil infiltration or kidney damage in a renal injury model, suggesting that other pathways or mechanisms might compensate for this metabolic loss during inflammation.
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The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(-/-) mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1) infection. CD200R1(-/-) peritoneal macrophages demonstrated a 70-75% decrease in the generation of IL-6 and CCL5 (Rantes) in response to the TLR2 agonist Pam(2)CSK(4) and to HSV-1.

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