Objective: Brown adipose tissue (BAT) is a therapeutic target for obesity. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is commonly used to quantify human BAT mass and activity. Detectable 18F-FDG uptake by BAT is associated with reduced prevalence of cardiometabolic disease.
View Article and Find Full Text PDFActivation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT.
View Article and Find Full Text PDFBackground: Liver transplantation (LT) offers patients with cirrhosis long-term survival, however many die from sepsis whilst awaiting LT. The liver's role in innate immunity may be key to improving outcomes, but the immune effects of LT have not been quantified.
Methods: Innate immune capacity was assessed by clearance of Tc-Albumin nanospheres in patients with chronic liver failure before and after LT.
Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by xenon washout.
View Article and Find Full Text PDFThe Sonic hedgehog (Shh) signalling pathway plays an important role in developmental patterning and proliferation. Recent evidence suggests that Shh also plays a role in the development of the immune system. Here, we demonstrate that components of the Shh signalling pathway are expressed in human macrophages and that the receptor for Shh, Ptc, is up-regulated by a commercially available recombinant preparation of Shh (CArShh).
View Article and Find Full Text PDFObjective: Acutely ischemic limbs are often of uncertain viability. To assist operative management, this study determined prospectively which indicators on admission were the best predictors of major amputation and, conversely, limb preservation.
Methods: Data were collected on admission.
The identification of Toll-like receptors has revolutionised our understanding of innate immunity. TLR4 transduces the LPS signal and that of a number of structurally and functionally unrelated agonists. However, recent evidence adds to longstanding concerns that endotoxin contamination of bacterially derived recombinant TLR4 agonists is responsible for effects attributed to these molecules.
View Article and Find Full Text PDFInfections represent a significant risk in the postoperative transplant recipient. The perfusion fluid used to perfuse and preserve the kidneys prior to transplantation represents a potential medium in which organisms can grow. The aim of this study was to determine the incidence and clinical relevance of bacterial contamination of perfusion fluid.
View Article and Find Full Text PDFVascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen, angiogenic factor and enhancer of vascular permeability. Expressed in the epithelial cells of the developing glomerulus and tubular epithelium, VEGF plays an important role in the development and maintenance of the early vasculature of the kidney. Here, we review the available literature regarding the expression and function of VEGF both in the developing and healthy adult kidney.
View Article and Find Full Text PDFIntroduced in the 18th century, hip disarticulation was considered to be one of the most radical operations performed for trauma or disease of the lower limb. The high morbidity and mortality associated with it ensured that it was a rarely performed procedure. It is fortunate that it remains extremely uncommon to the present day.
View Article and Find Full Text PDFSonic hedgehog (Shh) is important in the growth and differentiation of a variety of cell types, including the development of T cells in the thymus. This prompted us to investigate whether Shh signaling is a functional component of the physiological response of human mature CD4(+) T cells following Ag recognition. In this study, we demonstrate that Shh and its receptor Patched (Ptc) are expressed on resting and activated human peripheral CD4(+) T cells.
View Article and Find Full Text PDFIntroduction And Objective: Oesophago-gastric carcinoma is associated with a poor prognosis despite advances in diagnosis and treatment. Accurate preoperative staging of gastro-oesophageal carcinoma is, therefore, essential in order to determine patient selection for potentially curative resection. The aim of this study was to evaluate and compare the role of computerised tomography (CT), laparoscopic ultrasound (LapUS) and endoscopic ultrasound (EUS) in the staging of oesophago-gastric carcinoma.
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