Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation

Abstract: Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2–driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we examined whether RV-induced IL-25 could contribute to asthma exacerbations. RV-infected cultured asthmatic bronchial epithelial cells exhibited a heightened intrinsic capacity for IL-25 expression, which correlated with donor atopic status. In vivo human IL-25 expression was greater in asthmatics at baseline and during experimental RV infection. In addition, in mice, RV infection induced IL-25 expression and augmented allergen-induced IL-25. Blockade of the IL-25 receptor reduced many RV-induced exacerbation-specific responses including type 2 cytokine expression, mucus production, and recruitment of eosinophils, neutrophils, basophils, and T and non-T type 2 cells. Therefore, asthmatic epithelial cells have an increased intrinsic capacity for expression of a pro–type 2 cytokine in response to a viral infection, and IL-25 is a key mediator of RV-induced exacerbations of pulmonary inflammation.

Bayesian estimates of disease maps: How important are priors?

Abstract: In the fully Bayesian (FB) approach to disease mapping the choice of the hyperprior distribution of the dispersion parameter is a key issue. In this context we investigated the sensitivity of the rate ratio estimates to the choice of the hyperprior via a simulation study. We also compared the performance of the FB approach to mapping disease risk to the conventional approach of mapping maximum likelihood (ML) estimates and p-values. The study was modelled on the incidence data of insulin dependent diabetes mellitus (IDDM) as observed in the communes of Sardinia.

Steroid receptor expression in uterine natural killer cells.

Abstract: The endometrium contains a unique subset of uterine-specific natural killer (uNK) cells, the proposed functions of which include a role in decidualization, menstruation, and implantation. These cells increase in number during the mid-late secretory phase of the menstrual cycle and are also present in large numbers in early pregnancy. The cyclical nature of uNK cell appearance suggests hormonal regulation of these cells. To date, it has not been possible to localize either estrogen receptors (ERs) or progesterone receptors (PRs) to uNK cells. In the present study, we have investigated the steroid receptor expression of uNK cells, including not only ER alpha and PR but also wild-type ER beta 1, its variant form ER beta cx/beta 2, and glucocorticoid receptor (GR) using specific monoclonal antibodies and real-time quantitative RT-PCR. mRNA encoding ER alpha, PR, ER beta cx/beta 2, ER beta 1, and GR were identified in extracts of human endometrium across the menstrual cycle and in decidua. Quantitative real-time RT-PCR demonstrated an absence of ER alpha and PR mRNA in purified uNK cells. In contrast, mRNA for ER beta cx/beta 2, ER beta 1, and GR was present in uNK cells. ER alpha, PR, ER beta cx/beta 2, ER beta 1, and GR proteins were identified in endometrial and decidual biopsies. Colocalization using specific monoclonal antibodies confirmed that uNK cells were immunonegative for ER alpha and PR protein. These cells were also immunonegative for ER beta cx/beta 2 but did express ER beta 1 and GR proteins. These results raise the possibility that estrogens and glucocorticoids could be acting directly on uNK cells through ER beta and GR, respectively, to influence gene transcription in the endometrium and decidua.