Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

Stimulatory effects of opioids.

Abstract: Opioid receptors exist as three principle types, known as , and and have been recently reclassifed by an International Union of Pharmacology subcommittee as OP1( ), OP2( ) and OP3( ). All three receptors have been cloned, 45 87 99 and have pharmacological characteristics consistent with those of endogenous receptors. Multiple isoforms of each subtype have been proposed on pharmacological grounds but this remains controversial, as no subtypes have been identified using molecular biology techniques, although the possibility of post-translational modification of a common gene product remains. Opioid receptors belong to the family of guaninenucleotide-binding protein (G-protein) coupled receptors, consisting of seven transmembrane-spanning domains, an extracellular N-terminus, and an intracellular C-terminus. Such cell surface receptors have no direct contact with their final effector molecules. In this process receptors relay information via G proteins to activate effectqr proteins (fig. 1). G proteins are heterotrimeric membrane-associated proteins consisting of , and subunits. They are able to activate effector enzymes by a relatively straightforward process, the “G protein cycle” (fig. 2). Historically, G proteins are classified using two types of bacterial toxin, pertussis (PTX) and cholera (CTX). Pertussis toxin adenosine di-phosphate (ADP) ribosylates inhibitory G proteins (eg.Gi) and prevents interaction with the effector molecule. Cholera toxin prevents the GTP (Guanine–triphosphate) hydrolysis to GDP (Guanine–diphosphate) and therefore irreversibly activates -GTP of stimulatory G proteins (Gs). However, the use of G-protein subunit-specific antibodies has more accurately defined this classification. (For a review on G proteins, see Neer.) Both and subunits are able to activate G-protein-linked second-messenger systems. There are at least 16 types of subunit isoforms, along with at least seven and five isoforms, which allow for great diversity in G-protein signalling pathways. Common opioid receptor–G-protein-linked systems include adenylyl cyclase–cyclic adenosine monophosphate (cAMP), and phospholipase3 C (PLC)–inositol 1,4,5 trisphosphate (Ins(1,4,5)P3)-Ca . Adenylyl cyclase is the membrane-bound enzyme, of which

Peripartum changes in gastric emptying

Abstract: Summary Applied potential tomography was ilsed to measure changes in gastric emptying during the peripartum period. Gastric emptying was measured sequentially in each of 10 healthy patients at 37–40 weeks gestation, 2–3 days postpartum and after the 6-week postnatal assessment (control),‘Aean (SD) times to 50% emptying were 15 (6.05), 11 (5.9) and 15 (5.5) min, respectively. There was no statistically signijicant change in gastric emptying as a result of pregnancy in this group of women. Retrospective power analysis (assuming α= 0.05 and β= 0.20) shows the study design was adequate to detect a difference of 8 min.

New perspectives into the biological and clinical relevance of oestrogen receptors in the human breast.

Abstract: Oestrogen receptor (ER) is arguably the single most important biological predictive factor that exists today. In the last 10 years or so, however, our understanding of ER biology has undergone a paradigm shift following the identification of a second ER, ERβ, with the original ER being renamed ERα. A number of isoforms have additionally been described, especially for ERβ. Our knowledge of ER signalling has also increased with the recognition of accessory co-regulatory proteins, which help direct the transcriptional cascade. Here we outline these changes and discuss what biological and clinical implications these could have in the mammary gland. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The optimization of large-scale density gradient isolation of human islets

Abstract: The use of the COBE 2991 cell processor (COBE Laboratories, Colorado) for large-scale islet purification using discontinuous density gradients has been widely adopted. It minimizes many of the problems such as wall effects, normally encountered during centrifugation, and avoids the vortexing at interfaces that occurs during acceleration and deceleration by allowing the gradient to be formed and the islet-containing interface to be collected while continuing to spin. We have produced cross-sectional profiles of the 2991 bag during spinning which allow the area of interfaces in such step gradients to be calculated. This allows the volumes of the gradient media layers loaded on the machine to be adjusted in order to mazimize the area of the gradient interfaces. However, even using the maximal areas possible (144.5 cm2), clogging of tissue at such interfaces limits the volume of digest which can be separated on one gradient to 15 ml. We have shown that a linear continuous density gradient can be produced within the 2991 bag, that allows as much as 40 ml of digest to be successfully purified. Such a system combines the intrinsic advantages of the 2991 with those of continuous density gradients and provides the optimal method for density-dependent islet purification.