Paul A. Smith

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Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and(More)
Lymphocyte trafficking is critically regulated by the Sphingosine 1-phosphate receptor-1 (S1P(1)), a G protein-coupled receptor that has been highlighted as a promising therapeutic target in autoimmunity. Fingolimod (FTY720, Gilenya) is a S1P(1) receptor agonist that has recently been approved for the treatment of multiple sclerosis (MS). Here, we report(More)
We have examined the temporal relationship between intracellular Ca2+ concentration ([Ca2+]i) and secretion in single intact pancreatic β-cells. Secretion was detected as the release of 5-hydroxytryptamine from pre-loaded β-cells, using amperometry, and changes in [Ca2+]i were monitored by microfluorimetry. Stimulation of β-cells by elevation of the(More)
OBJECTIVES To investigate the seroconversion rate and duration of persistence of protective antibody titres after varicella immunisation in children with renal failure. DESIGN 32 children (25 end stage and 7 pre-end stage renal failure) were immunised using 2 x 2,000 plaque forming unit doses of varicella vaccine 3 months apart. Varicella antibody titres(More)
BACKGROUND Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY[3-36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropeptide Y is noted for its orexigenic effect following(More)
The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow(More)
OBJECTIVE The current set of studies describe the in vivo metabolic actions of the novel amylin-mimetic peptide davalintide (AC2307) in rodents and compares these effects with those of the native peptide. RESEARCH DESIGN AND METHODS The anti-obesity effects of davalintide were examined after intraperitoneal injection or sustained peripheral infusion(More)
The paracaspase MALT1 plays an important role in immune receptor-driven signaling pathways leading to NF-κB activation. MALT1 promotes signaling by acting as a scaffold, recruiting downstream signaling proteins, as well as by proteolytic cleavage of multiple substrates. However, the relative contributions of these two different activities to T and B cell(More)
OBJECTIVES This study planned to establish whether sympathetic hyperactivity exists in white-coat hypertension (WHT) in the clinical setting, relative to matched groups with normotension (NT) and untreated essential hypertension (EHT). BACKGROUND White-coat hypertension differs from EHT by the presence of normal ambulatory blood pressure. Sympathetic(More)