114 research outputs found

    Calm Vessels: Cultural Expectations of Pregnant Women in Qatar

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    This article explores emerging themes from the first stage of ethnographic research investigating pregnancy and loss in Qatar. Issues around the development of foetal personhood, the medical management of the pregnant body and the social role of the pregnant woman are explored. Findings suggest that Qatari women are expected to be calm vessels for their growing baby and should avoid certain foods and behaviours. These ideas of risk avoidance are linked to indigenous knowledge around a mother’s influence on a child’s health and traits. Motherhood holds a particularly important place in Qatari culture and in Islam, and women are ultimately responsible for protecting and promoting fertility and for producing healthy children

    CD103 Deficiency Prevents Graft-versus-Host Disease but Spares Graft-versus-Tumor Effects Mediated by Alloreactive CD8 T Cells

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    Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis

    T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

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    Pancreatic cancer is an aggressive and potent disease, which is largely resistant to conventional forms of treatment. However, the discovery of antigens associated with pancreatic cancer cells has recently suggested the possibility that immunotherapy might become a specific and effective therapeutic option. T cells within many epithelia, including those of the pancreas, are known to express the αEÎČ7-integrin adhesion molecule, CD103. The only characterised ligand for CD103 is E-cadherin, an epithelial adhesion molecule which exhibits reduced expression in pancreatic cancer. In our study, CD103 was found to be expressed only by activated T cells following exposure to tumour necrosis factor beta 1, a factor produced by many cancer cells. Significantly, the expression of this integrin was restricted mainly to class I major histocompatibility complex-restricted CD8+ T cells. The human pancreatic cancer cell line Panc-1 was transfected with human E-cadherin in order to generate E-cadherin negative (wild type) and positive (transfected) sub-lines. Using a sensitive flow cytometric adhesion assay it was found that the expression of both CD103 (on T cells) and E-cadherin (on cancer cells) was essential for efficient adhesion of activated T cells to pancreatic cancer cells. This adhesion process was inhibited by the addition of antibodies specific for CD103, thereby demonstrating the importance of the CD103→E-cadherin interaction for T-cell adhesion. Using a 51Cr-release cytotoxicity assay it was found that CD103 expressing T cells lysed E-cadherin expressing Panc-1 target cells following T cell receptor stimulation; addition of antibodies specific for CD103 significantly reduced this lysis. Furthermore, absence of either CD103 from the T cells or E-cadherin expression from the cancer cells resulted in a significant reduction in cancer cell lysis. Therefore, potentially antigenic pancreatic cancer cells could evade a local anti-cancer immune response in vivo as a consequence of their loss of E-cadherin expression; this phenotypic change may also favour metastasis by reducing homotypic adhesion between adjacent cancer cells. We conclude that effective immunotherapy is likely to require upregulation of E-cadherin expression by pancreatic cancer cells or the development of cytotoxic immune cells that are less dependent on this adhesion molecule for efficient effecter function

    TGFÎČR signalling determines CD103<sup>+</sup>CD11b<sup>+</sup> dendritic cell development in the intestine

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    CD103+CD11b+ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFÎČR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103−CD11b+ dendritic cell subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103−CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T cells in vitro and in vivo, and by reduced numbers of endogenous Th17 cells in the intestinal mucosa. Thus, TGFÎČR1-mediated signalling may explain the tissue-specific development of these unique DCs

    Reservists and veterans: Viewed from within and without

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    This chapter describes two important groups relative to military service – reservists and veterans. Definitions are provided regarding who is a member of each group. A summary of past and current research findings for each group is provided. The summary is organized by investigative topics or themes, which provide the current scope of the field for reservists and for veterans. Finally, approaches to the study of reservists and veterans are described, along with challenges – both substantively and methodologically – for future research studies. These serve as fertile areas for improvements and investigations in future research studies

    International Lower Limb Collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

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    International Lower Limb Collaborative (INTELLECT) study : a multicentre, international retrospective audit of lower extremity open fractures

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    Reservists and Veterans: Viewed from Within and Without

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    This is the final version. Available from Springer via the DOI in this record. This chapter describes two important groups relative to military service – reservists and veterans. Definitions are provided regarding who is a member of each group. A summary of past and current research findings for each group is provided. The summary is organized by investigative topics or themes, which provide the current scope of the field for reservists and for veterans. Finally, approaches to the study of reservists and veterans are described, along with challenges – both substantively and methodologically – for future research studies. These serve as fertile areas for improvements and investigations in future research studies

    Local-level determinants of wildcat occupancy in Northeast Scotland

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    We studied the influence of food abundance, land cover and disturbance on European wildcat (Felis silvestris silvestris Schreber, 1777) presence in Scotland. Wildcat records were collected using camera trapping, and prey data were assessed through linear transects and small mammal trapping. Surveys were carried out in three study areas in northeast Scotland. Wildcat occupancy was best predicted by a combination of food and land cover variables. This species detection was associated with higher rodent abundance and areas of higher habitat diversity encompassing patches of mixed and coniferous woodlands. Wildcat presence was negatively linked with the prevalence of dwarf shrub areas. We suggest that wildcat conservation actions at local scale should take into account the availability of feeding resources and landscape heterogeneity. © 2013 Springer-Verlag Berlin Heidelberg
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