AMU patient list generation: from junior scribe to junior doctor.

This quality improvement project (QIP) aimed to assess the impact of automating patient list generation on the acute medical unit (AMU) at Sandwell and West Birmingham Hospitals NHS Trust. The AMU patient list categorises patients requiring 'clerking', 'post-take' (PTWR) and 'post-post-take' (PPTWR) for the morning ward round. During weekdays, this list need only include the patients in AMU.

Mouse Hemokinin-1 Decapeptide Subjected to a Brain-specific Post-translational Modification.

Background/aim: The tachykinin mouse hemokinin-1, expressed by the mouse Tac4 gene, produces either analgesia or nociception, interacting with the neurokinin 1 receptor. TAC4 precursor processing is not identical to the processing of the TAC1 precursor, for the release of substance P (amidated undecapeptide). The characterization of the mouse hemokinin-1 sequence was required.

Molecular characterization of host-parasite cell signalling in Schistosoma mansoni during early development.

During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The 'somules' next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such 'transactivation' by host factors in schistosomes is not well defined.

Sensory Protein Kinase Signaling in Schistosoma mansoni Cercariae: Host Location and Invasion.

Schistosoma mansoni cercariae display specific behavioral responses to abiotic/biotic stimuli enabling them to locate and infect the definitive human host. Here we report the effect of such stimulants on signaling pathways of cercariae in relation to host finding and invasion. Cercariae exposed to various light/temperature regimens displayed modulated protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) activities, with distinct responses at 37 °C and intense light/dark, when compared to 24 °C under normal light.

Protein kinase C and extracellular signal-regulated kinase regulate movement, attachment, pairing and egg release in Schistosoma mansoni.

Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using 'smart' antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S.

Neurokinin B and pre-eclampsia: a decade of discovery.

At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding.

Immunochemical methods for the peptidomic analysis of tachykinin peptides and their precursors.

The tachykinins represent the largest known peptide family and are responsible for a range of pleiotropic functions in both vertebrates and invertebrates. Recent research has shown a diversity of mechanisms such as mRNA splicing, precursor processing and post-translation modification that can lead to a complex and continually expanding repertoire of tachykinin peptides. The peptidomic analysis of the tachykinins has been hindered by the lack of specific methodologies to capture, purify and characterise each tachykinin.

Differential mRNA splicing and precursor processing of neurokinin B in neuroendocrine tissues.

The tachykinin neurokinin B which is encoded on the tachykinin 3 precursor, has prominent roles in both neuronal and endocrine systems, yet little is known about its evolution, potential splice variants and the manner in which it is processed. Here, we deduce the diversity within the vertebrate tachykinin 3 precursors, and identify novel tachykinin 3 splice variants and precursors. A total of 35 different tachykinin 3 precursors were identified in mammals, birds and reptiles.

Functional characterisation of hemokinin-1 in mouse uterus.

The preprotachykinin gene Tac4 expressed in murine uterus and placenta is thought to encode a peptide RSRTRQFYGLM-NH(2), mouse hemokinin 1. We have examined the uterotonic effects of mouse hemokinin 1 and its N-terminally truncated analogue, mouse hemokinin 1(2-11) on mouse uterus. Mouse hemokinin 1(2-11) was equieffective with but slightly less potent than substance P in tissues from non-pregnant Swiss mice.

Polymorphisms in the Apolipoprotein L1 gene and their effects on blood lipid and glucose levels in middle age males.

Apolipoprotein L1 in plasma is associated with high-density lipoprotein. Novel APOL1 polymorphisms are investigated along with the association of two common haplotypes (Lysl66Glu, Ile244Met, Lys271Arg) with circulating lipid and glucose levels. Although the amino acid substitutions occur in the amphipathic alpha helices region involved in lipid binding, these substitutions were found not to independently account for variability in circulating lipid and glucose levels in 149 middle age males.

Characterization of the gene structures, precursor processing and pharmacology of the endokinin peptides.

The endokinins represent several species-divergent and peripherally located mammalian tachykinins (hemokinin-1 in mouse and rat, endokinin-1 in rabbit and endokinins A and B in humans) and also the tachykinin gene-related peptides. These peptides are all encoded on the preprotachykinin 4 (TAC4) gene. Their complementary DNA sequences, gene structures and expression profiles have been determined from a number of different mammalian species.

Regulation of the stimulant actions of neurokinin a and human hemokinin-1 on the human uterus: a comparison with histamine.

Regulation of the contractile effects of tachykinins and histamine on the human uterus was investigated with biopsy sections of the outer myometrial layer. The effects of neurokinin A (NKA) and human hemokinin-1 (hHK-1) in tissues from pregnant but not from nonpregnant women were enhanced by the inhibition of neprilysin. The effects of NKA and eledoisin were blocked by the NK2 receptor antagonist SR 48968 but not by the NK1 receptor antagonist SR 140333 in tissues from both groups of women.

New challenges in the study of the mammalian tachykinins.

There is an expanding repertoire of mammalian tachykinins produced by a variety of tachykinin genes, gene splicing events and peptide processing. Novel tachykinin-binding molecules/receptors are proposed, but only, three tachykinin receptors are identified with certainty. The question remains - do more tachykinin receptors exist or is there just the need to reappraise our understanding of the known receptors? The tachykinin NK1 receptor, the preferred receptor for both substance P and the peripheral SP-like endokinins, exists in several tissue-specific conformations and isoforms and may provide some clues.

Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus.

The aim of this study was to analyze the function and expression of tachykinins, tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to tachykinins in uteri of late pregnant mice.

Tachykinins regulate the function of platelets.

Evidence has been mounting for peripheral functions for tachykinins, a family of neuropeptides including substance P (SP), neurokinin A, and neurokinin B, which are recognized for their roles in the central and peripheral nervous system. The recent discovery of 4 new members of this family, the endokinins (EKA, B, C, and D), which are distributed peripherally, adds support to the notion that tachykinins have physiologic/endocrine roles in the periphery. In the present study we report a fundamental new function for tachykinins in the regulation of platelet function.

Characterization of the endokinins: human tachykinins with cardiovascular activity.

We report four human tachykinins, endokinins A, B, C, and D (EKA-D), encoded from a single tachykinin precursor 4 gene that generates four mRNAs (alpha, beta, gamma, and delta). Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected. EKA/B 10-mers displayed equivalent affinity for the three tachykinin receptors as substance P (SP), whereas a 32-mer N-terminal extended form of EKB was significantly more potent than EKA/B or SP.

Emerging molecular targets for the treatment of pre-eclampsia.

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. It is also one of the major causes of iatrogenic prematurity among new born babies, placing a heavy burden on both prospective parents and on the health service. The mild form of PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive complications, which can involve the maternal liver, kidneys, lungs, blood and platelet coagulation and nervous systems.

The endocrinology of pre-eclampsia.

Pre-eclampsia is a pregnancy specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy associated deaths, and is one of the major causes of iatrogenic prematurity among new born babies. The mild form of pre-eclampsia most commonly presents with the features of maternal hypertension and proteinuria, but can swiftly and unpredictably become severe with numerous multisystem complications involving the maternal liver, kidneys, lungs, blood and platelet coagulation and nervous systems. The diverse symptoms of pre-eclampsia have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms.

Placental peptides as markers of gestational disease.

The human placenta produces a wide range of important peptides, of which an intricate balance is required throughout pregnancy. In a gestational disease, this balance may be disturbed and the identification of such changes may be used to detect a particular pathology or to ascertain its severity. This review considers the role and association of various placental peptide markers associated with the major gestational diseases including intrauterine growth retardation, pre-term labour, pre-eclampsia, chromosomal disorders, gestational diabetes and trophoblastic disease.

The human tachykinin NK1 (short form) and tachykinin NK4 receptor: a reappraisal.

Excessive secretion of placental neurokinin B into the circulation during the third trimester of pregnancy is seen in women with preeclampsia. To determine a role for neurokinin B, we have used a number of different animal models to ascertain the expression of the three tachykinin receptors (NK1--both short and long forms, NK2 and NK3) and the putative human tachykinin NK4 receptor in the placenta. Human and rat placenta express all three classical tachykinin receptors.