306 research outputs found

    Role of complement in in vitro and in vivo lung inflammatory reactions

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    Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing on the complement activation products, C5a, and the membrane attack complex, C5b‐9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement‐induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products. J. Leukoc. Biol. 64: 40–48; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142061/1/jlb0040.pd

    ‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

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    Forest biodiversity studies conduct Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisal barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning. Inclusive Conservation Participatory planning Governance Visions Visual methods Participatory methods d across Europe use a multitude of forestry terms, often inconsistently. This hinders the comparability across studies and makes the assessment of the impacts of forest management on biodiversity highly context-dependent. Recent attempts to standardize forestry and stand description terminology mostly used a top-down approach that did not account for the perspectives and approaches of forest biodiversity experts. This work aims to establish common standards for silvicultural and vegetation definitions, creating a shared conceptual framework for a consistent study on the effects of forest management on biodiversity. We have identified both strengths and weaknesses of the silvicultural and vegetation information provided in forest biodiversity studies. While quantitative data on forest biomass and dominant tree species are frequently included, information on silvicultural activities and vegetation composition is often lacking, shallow, or based on broad and heterogeneous classifications. We discuss the existing classifications and their use in European forest biodiversity studies through a novel bottom-up and top-driven review process, and ultimately propose a common framework. This will enhance the comparability of forest biodiversity studies in Europe, and puts the basis for effective implementation and monitoring of sustainable forest management policies. The standards here proposed are potentially adaptable and applicable to other geographical areas and could be extended to other forest interventions.publishedVersio

    ‘Bonkers but good!’ – Using illustration-based interview methods to understand land management and conservation visions

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    Visions help to understand common ground and tensions among citizens and stakeholders, supporting inclusive land management and conservation solutions to the climate emergency and biodiversity crisis. With careful design and sufficient resource, it is possible to bring together communities and other stakeholders to share perspectives and deliberate desired futures, identifying more acceptable alternatives and avoiding costly delays. We evaluated researcher and participant experiences of illustration-based interviews to understand land management visions using four studies in Scotland, The Netherlands and Spain. These studies used STREAMLINE, a visual mixed-method interview format using thematic illustrated canvases designed to provide an inclusive and creative framing for participants to contemplate their desired future. Participants enjoyed the informal visual format, which reduced pressure, increased comfort through the research process, and helped their thinking and reflection about complex topics. They also valued being listened to and having the opportunity to share their views. Researchers appreciated the ability to triangulate rich qualitative data with a variety of quantitative measure through the mixed-method format and the flexibility to adapt the canvases to suit their research aims. Positive participant experience made facilitation easier and was stimulating for the researchers. The credibility and legitimacy of illustration-based interviews will ultimately depend on specific research design-decisions and testing, which can make the approach more resource intensive than conventional interviews. While organisational barriers should be considered realistically, illustration-based interviews can have high saliency by providing useful and usable insights that strengthen land management policy and planning

    Upregulation of Phagocyte-Derived Catecholamines Augments the Acute Inflammatory Response

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    Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages) are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFÎșB in macrophages, causing enhanced release of proinflammatory cytokines (TNFα, IL-1ÎČ, IL-6). Both adrenal-intact (AD+) and adrenalectomized (ADX) rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-ÎČ-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI). Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to α2-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFÎșB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of α2-adrenoceptors

    Regulatory effects of interleukin‐11 during acute lung inflammatory injury

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    The role of interleukin‐11 (IL‐11) was evaluated in the IgG immune complex model of acute lung injury in rats. IL‐11 mRNA and protein were both up‐regulated during the course of this inflammatory response. Exogenously administered IL‐11 substantially reduced, in a dose‐dependent manner, the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin. These in vivo anti‐inflammatory effects of IL‐11 were associated with reduced NF‐ÎșB activation in lung, reduced levels of tumor necrosis factor α (TNF‐α) in bronchoalveolar lavage (BAL) fluids, and diminished up‐regulation of lung vascular ICAM‐1. It is interesting that IL‐11 did not affect BAL fluid content of the CXC chemokines, macrophage inflammatory protein‐2 (MIP‐2) and cytokine‐inducible neutrophil chemoattractant (CINC); the presence of IL‐11 did not affect these chemokines. However, BAL content of C5a was reduced by IL‐11. These data indicate that IL‐11 is a regulatory cytokine in the lung and that, like other members of this family, its anti‐inflammatory properties appear to be linked to its suppression of NF‐ÎșB activation, diminished production of TNF‐α, and reduced up‐regulation of lung vascular ICAM‐1. J. Leukoc. Biol. 66: 151–157; 1999.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141937/1/jlb0151.pd

    Cytokine and Adhesion Molecule Requirements for Lung Injury Induced by Anti-Glomerular Basement Membrane Antibody

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    Acute hemorrhagic lung injury occurs in humans with anti-GBM antibody (Goodpasture's syndrome), however, the mechanism of this injury is still largely unknown. To date, treatment has been confined to steroids and plasmaphoresis. Infusion of anti-GBM antibody into rats caused lung injury with intra-alveolar hemorrhage and intrapulmonary accumulation of neutrophils. Lung injury was dependent on the presence of neutrophils and complement and required both TNFα and IL-1. Experiments employing blocking antibodies to adhesion molecules demonstrated requirements for the ÎČ 1 integrin VLA-4, ÎČ 2 integrins LFA-1 and Mac-1, and L-selectin. The endothelial cell adhesion molecules, E-selectin and ICAM-1, were also required for the full development of lung injury. Inhibition of TNFα or IL-1 or adhesion molecules reduced both lung injury and tissue neutrophil accumulation. Thus, this study underscores cytokine and adhesion molecule requirements for neutrophil mediated injury in lung and kidney caused by anti-GBM, suggesting potential targets for the treatment of Goodpasture's syndrome in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44520/1/10753_2004_Article_416573.pd

    The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease

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    Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications

    Central memory CD8+ T lymphocytes mediate lung allograft acceptance

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    Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8(+) T cells (CD44(hi)CD62L(hi)CCR7(+)). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8(+) T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8(+) central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung

    Treatment of eccrine porocarcinoma with metastasis to the parotid gland using intensity-modulated radiation therapy: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Cutaneous eccrine porocarcinomas are uncommon malignant tumors of the sweat gland.</p> <p>Case Presentation</p> <p>A 76-year-old Caucasian man presented to our hospital with a left temporal mass. We describe a case of eccrine porocarcinoma with metastasis to the parotid gland with special emphasis on the role of surgical resection and adjuvant radiation therapy.</p> <p>Conclusion</p> <p>Besides surgical resection, little is known about the role of adjuvant therapy in managing eccrine porocarcinomas. Radiation therapy should be considered within a multidisciplinary approach in patients with primary or recurrent eccrine porocarcinomas.</p
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