Amy Wilcock

Mast cells are typically linked to immediate hypersensitivity and anaphylaxis. This review looks beyond this narrow role, focusing on how these cells have evolved and diversified via natural selection promoting serine protease gene duplication, augmenting their innate host defense function against helminths and snake envenomation. Plasticity of mast cell genes has come at a price. Somatic activating mutations in the mast cell growth factor KIT gene cause cutaneous mastocytosis in young children and systemic mastocytosis with a more guarded prognosis in adults who may also harbor other gene mutations with oncogenic potential as they age. Allelic TPSAB1 gene duplication associated with higher basal mast cell tryptase is possibly one of the commonest autosomal dominantly inherited multi-system diseases affecting the skin, gastrointestinal tract, circulation and musculoskeletal system. Mast cells are also establishing a new-found importance in severe asthma, and in remodeling of blood vessels in cancer and atherosclerotic vascular disease. Furthermore, recent evidence suggests that mast cells sense changes in oxygen tension, particularly in neonates, and that subsequent degranulation may contribute to common lung, eye, and brain diseases of prematurity classically associated with hypoxic insults. One hundred and forty years since Paul Ehrlich's initial description of "mastzellen," this review collates and highlights the complex and diverse roles that mast cells play in health and disease.

OBJECTIVE: No single diagnostic investigation is currently available for necrotising enterocolitis (NEC). We implemented a novel, untargeted, exploratory study to determine whether metabolomics can reveal early biomarker(s) of NEC. The effect of gestational age on the metabolome was also investigated. METHODS: Two serum samples were obtained from 12 preterm babies (born <30 weeks gestation) and eight term controls: sample "A" at ≤1 week of age and sample "B" once fully fed. Samples were subjected to gas chromatography-mass spectrometry. Metabolomic data was analysed by principal component analysis (PCA), univariate and network analysis. RESULTS: Sixteen metabolite features significantly differed when B samples were compared between preterm babies who subsequently developed NEC and preterm/term controls (p value <0.05). Of these seven metabolites were linked to up-regulation of IL-1β. Significant differences in 54 metabolite features (p value <0.05) were observed between preterm and term metabolomes. Of these, 12 metabolite features were linked to one network involved in carbohydrate/lipid metabolism (p = 1 × 10(-30)). CONCLUSIONS: Metabolomic differences were observed in preterm babies at risk of NEC. However, sample sizes were insufficient to confidently identify a biomarker. Network modelling of preterm and term metabolomes suggest possible nutritional deficiency and altered pro-insulin action in preterm babies.

SUMMARY An analysis of deformities of the renal tract in a survey of 4, 500 necropsies in children showed an overall prevalence of renal tract deformities in 7.8 per cent. When the renal tract deformities were analysed in relation to the presence of meningomyeloceles, it was found that the incidence in the latter was 29 per cent. overall, ranging from 25 per cent. at birth to 58 per cent. at between the ages of 3 and 5 years. The types of deformity seen in children with meningomyeloceles are similar to those in children without meningomyelocele but there is an added factor of dilatation deformity developing later.