EMP2 regulates angiogenesis in endometrial cancer cells through induction of VEGF.

Understanding tumor-induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study, we define a novel function for epithelial membrane protein-2 (EMP2) in the control of angiogenesis. EMP2 functions as an oncogene in endometrial cancer, and its expression has been linked to decreased survival. Using endometrial cancer xenografts, modulation of EMP2 expression resulted in profound changes to the tumor microvasculature. Under hypoxic conditions, upregulation of EMP2 promoted vascular endothelial growth factors (VEGF) expression through a HIF-1α-dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1α and VEGF expression with the net consequence of poorly vascularized tumors in vivo. We have previously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction of tumor load, and since then we have constructed a fully human EMP2 IgG1. Treatment of endometrial cancer cells with EMP2-IgG1 reduced tumor load with a significant improvement in survival. These results support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo

Blood culture collection technique and pneumococcal surveillance in Malawi during the four year period 2003–2006: an observational study

BACKGROUND: Blood culture surveillance will be used for assessing the public health effectiveness of pneumococcal conjugate vaccines in Africa. Between 2003 and 2006 we assessed blood culture outcome and performance in adult patients in the central public hospital in Blantyre, Malawi, before and after the introduction of a dedicated nurse led blood culture team. METHODS: A prospective observational study. RESULTS: Following the introduction of a specialised blood culture team in 2005, the proportion of contaminated cultures decreased (19.6% in 2003 to 5.0% in 2006), blood volume cultured increased and pneumococcal recovery increased significantly from 2.8% of all blood cultures to 6.1%. With each extra 1 ml of blood cultured the odds of recovering a pneumococcus increased by 18%. CONCLUSION: Standardisation and assessment of blood culture performance (blood volume and contamination rate) should be incorporated into pneumococcal disease surveillance activities where routine blood culture practice is constrained by limited resources

Computing power of quantitative trait locus association mapping for haploid loci

<p>Abstract</p> <p>Background</p> <p>Statistical power calculations are a critical part of any study design for gene mapping. Most calculations assume that the locus of interest is biallelic. However, there are common situations in human genetics such as X-linked loci in males where the locus is haploid. The purpose of this work is to mathematically derive the biometric model for haploid loci, and to compute power for QTL mapping when the loci are haploid.</p> <p>Results</p> <p>We have derived the biometric model for power calculations for haploid loci and have developed software to perform these calculations. We have verified our calculations with independent mathematical methods.</p> <p>Conclusion</p> <p>Our results fill a need in power calculations for QTL mapping studies. Furthermore, failure to appropriately model haploid loci may cause underestimation of power.</p

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver

This work was funded by a Wellcome Trust Investigator Award to MKM funding KS and LP, MRC Career Development Award to CD, MRC Clinical Research Training Fellowship to DP, Wellcome Trust Henry Dale Fellowship to VM

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

Suspected idiopathic sclerosing orbital inflammation presenting as immunoglobulin G4-related disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Idiopathic sclerosing orbital inflammation is a rare and ill-defined heterogeneous entity, and a distinct subset of orbital inflammation. Recently, attention has been focused on immunoglobulin G4-related disease complicated with fibrotic changes in some other organs with high serum immunoglobulin G4 levels. This report presents a case of suspected idiopathic sclerosing orbital inflammation complicated with high serum immunoglobulin G4 levels.</p> <p>Case presentation</p> <p>An 82-year-old Japanese woman had a 30-year history of chronic thyroiditis. She experienced right ptosis and eyelid swelling. These symptoms gradually developed over five years. The clinical and radiographic findings suggested that our patient had idiopathic sclerosing orbital inflammation. We were unable to obtain our patient's consent to perform a biopsy. While the serum immunoglobulin G level was within the normal limits, the serum immunoglobulin G4 level was significantly elevated. The serum immunoglobulin G4 levels decreased after the administration of oral prednisolone at a daily dose of 20 mg. In addition, the swelling and ptosis of the right upper eyelid disappeared gradually after four weeks. Our patient was then suspected to have idiopathic sclerosing orbital inflammation complicated with immunoglobulin G4-related disease and chronic thyroiditis.</p> <p>Conclusion</p> <p>An orbital pseudotumor of this type is indicative of idiopathic sclerosing orbital inflammation immunoglobulin G4-related disease. Immunoglobulin G4 may thus be considered a subclass of immunoglobulin G when the serum immunoglobulin G level is within normal limits.</p