70 research outputs found

    Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation

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    The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161+ CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn's disease (CD), these CD161+ cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161+ CD4 T cells from CD patients readily produce IL-17 and interferon γ upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1β was required to enable IL-23–induced cytokine release. Circulating CD161+ Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin β7 expression. Supporting their colitogenic phenotype, CD161+ Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161+ CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation

    Multigroup Ethnic Identity Measure (MEIM) Expansion: Measuring Racial, Religious, and National Aspects of Sense of Ethnic Identity Within the United Kingdom

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    These studies examined the degree to which racial, religious, and national aspects of individuals' sense of ethnic identity stand as interrelated, yet distinct, constructs. Results of exploratory factor analyses in Study 1 (n = 272) revealed that a three-factor model specifying racial, religious, and national identities yielded optimal fit to correlational data from an expanded, 36-item version of the Multigroup Ethnic Identity Measure (MEIM; Roberts et al., 1999), although results left room for improvement in model fit. Subsequently, results of confirmatory factor analyses in Study 2 (n = 291) revealed that, after taking covariance among the items into account, a six-factor model specifying exploration and commitment dimensions within each of the racial, religious, and national identity constructs provided optimal fit. Implications for the utility of Goffman's (1963b) interactionist role theory and Erikson's (1968) ego psychology for understanding the full complexity of felt ethnic identity are discussed

    Reduction of Natural Killer but Not Effector CD8 T Lymphoyctes in Three Consecutive Cases of Severe/Lethal H1N1/09 Influenza A Virus Infection

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    Background: The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. Methodology/Principal Findings: We present the cellular immunology profile in the blood, and detailed clinical (and postmortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. Conclusion/Significance: Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype

    The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

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    Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

    Syntheses and reaction in organic chemistry

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    ix, 547 p.; 27 cm

    The Synthesis of Thienothianaphthene Derivatives by Ring Formation with Sulfur 1

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