3,451 research outputs found
Rev. Perry C. Bramlett Collection
No full textFinding aid of the Rev. Perry C. Bramlett manuscript collectionA graduate of Southern Seminary in Louisville, Kentucky; a noted author; and a dedicated and respected scholar, Rev. Perry C. Bramlett�s life work was taking C. S. Lewis to the local church. His widow, Joan Fine Bramlett of Fairhope, Alabama, selected Mercer University to house this collection to honor Bramlett�s work, to share the significance of Bramlett�s life, and to mark his contributions to the scholarship of C. S. Lewis and his friends and their influences
Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats.
No full textIn adult rats, 50,000 units of recombinant interleukin-1 beta (IL-1 beta) injected into the brain parenchyma produced an intense meningitis and disruption of the blood-CSF barrier by 4 h. No increase in vascular permeability to horseradish peroxidase or leukocyte recruitment was observed at the site of injection. By contrast, in juvenile rats, 100 units of IL-1 beta injected into the striatum gave rise to a large increase in blood-brain barrier permeability and recruitment of polymorphonuclear neutrophils into the tissue around the injection site by 4 h. This effect was also accompanied by a marked meningitis. The injection of 100 units of IL-1 beta into neonatal (2-h-old) rats gave rise to an increase in permeability of vessels to serum proteins in the meninges, but no increase in vascular permeability was observed at the injection site. The IL-1 beta-induced increases in vessel permeability in the meninges, parenchyma, and choroid plexus were polymorphonuclear neutrophil dependent, since leukocyte depletion by irradiation or polymorphonuclear neutrophil anti-serum pre-treatment eliminated the response in the juvenile animals and in the adults. Seventy-five thousand units of murine tumour necrosis factor-alpha injected into the parenchyma of both adults and juvenile animals failed to induce an increase in blood-brain barrier permeability or polymorphonuclear neutrophil recruitment, but did give rise to a mild meningitis. These findings demonstrate clear differences in the responsiveness of different CNS compartments to IL-1 beta. Furthermore, while tumour necrosis factor-alpha and IL-1 beta might have been expected to exhibit similar proinflammatory effects in the CNS, this is not the case. We also show, for the first time, that age has a significant effect on the response to a cytokine. The "window of susceptibility' to an inflammatory stimulus in juvenile rats, if paralleled in humans, may be a major factor in the increased susceptibility of children to trauma or to infectious insults to the CNS
Cytokine-induced acute inflammation in the brain and spinal cord
No full textDifferent compartments in the central nervous system mount distinct inflammatory responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in a manner reminiscent of a peripheral inflammatory response, whereas the brain parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and secondary tissue destruction. Unexpectedly, these phenomena are generally more pronounced in the parenchyma of the spinal cord than in the parenchyma of the brain. To investigate whether these differences between brain and spinal cord can be attributed, at least in part, to differing sensitivities to proinflammatory cytokines, we stereotactically injected recombinant rat (rr) TNF[alpha] or rrIL-1[beta] into the striatum or the spinal cord of Wistar rats. In the brain, the injection of rrTNF[alpha] failed to evoke BBB breakdown or leukocyte recruitment, whereas in the spinal cord injection of TNF[alpha] resulted in marked BBB breakdown and leukocyte recruitment. Similarly, the injection of rrIL-1[beta] into the brain parenchyma failed to induce BBB breakdown and gave rise to only minimal neutrophil recruitment, whereas the injection of rrIL-1[beta] into the spinal cord induced significant BBB breakdown and recruitment of neutrophils and lymphocytes. Thus, using a minimally invasive injection technique, equivalent in both circumstances, we have shown that there are marked differences in the inflammatory response between the brain parenchyma and spinal cord parenchyma. This observation has important implications for the treatment of spinal cord injuries
Phylogenetic relationships of geckos of the Hemiphyllodactylus harterti group, a new species from Penang Island, Peninsular Malaysia, and a likely case of true cryptic speciation
No full textCobos, Anthony, Grismer, L. Lee, Wood, Perry L., Quah, Evan S. H., Anuar, Shahrul, Muin, Mohd Abdul (2016): Phylogenetic relationships of geckos of the Hemiphyllodactylus harterti group, a new species from Penang Island, Peninsular Malaysia, and a likely case of true cryptic speciation. Zootaxa 4107 (3): 367-380, DOI: 10.11646/zootaxa.4107.3.
Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration
No full textMicroglia, the resident immune cells of the central nervous system (CNS), play an important role in CNS homeostasis during development, adulthood and ageing. Their phenotype and function have been widely studied, but most studies have focused on their local interactions in the CNS. Microglia are derived from a particular developmental niche, are long-lived, locally replaced and form a significant part of the communication route between the peripheral immune system and the CNS; all these components of microglia biology contribute to maintaining homeostasis. Microglia function is tightly regulated by the CNS microenvironment, and increasing evidence suggests that disturbances, such as neurodegeneration and ageing, can have profound consequences for microglial phenotype and function. We describe the possible biological mechanisms underlying the altered threshold for microglial activation, also known as 'microglial priming', seen in CNS disease and ageing and consider how priming may contribute to turning immune-to-brain communication from a homeostatic pathway into a maladaptive response that contributes to symptoms and progression of diseases of the CNS
Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation
No full textMost pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin-1? (IL-1?) from resident and infiltrating cells. The IL-1 type I receptor (IL-1RI) initiates a signalling cascade but the type II receptor (IL-1RII) acts as a decoy receptor. Here we have investigated the expression of IL-1?, IL-1RI and IL-1RII in distinct inflammatory lesions in the rat brain. IL-1? was injected into the brain to generate an inflammatory lesion in the absence of neuronal cell death whereas neuronal death was specifically induced by the microinjection of N-methyl-d-aspartate (NMDA). Using TaqMan RT-PCR and ELISA, we observed elevated de novo IL-1? synthesis 2 h after the intracerebral microinjection of IL-1?; this de novo IL-1? remained elevated 24 h later. There was a concomitant increase in IL-1RI mRNA but a much greater increase in IL-1RII mRNA. Immunostaining revealed that IL-1RII was expressed on brain endothelial cells and on infiltrating neutrophils. In contrast, although IL-1? and IL-1RI were elevated to similar levels in response to NMDA challenge, the response was delayed and IL-1RII mRNA expression was unchanged. The lesion-specific expression of IL-1 receptors suggests that the receptors are differentially regulated in a manner not directly related to the endogenous level of IL-1 in the CNS.<br/
Hepatic CC chemokines control the magnitude of the inflammatory response within the injured rodent brain
No full textHepatic CXC chemokines, behaving as acute phase proteins, regulate neutrophil mobilisation and recruitment following focal IL-1h-mediated inflammation to the rat brain. To determine whether this response was specific to CXC chemokines or whether it represented a more generalised response to acute brain inflammation, we examined brain and liver production of MCP-1, a CC chemokine, when rats were microinjected with TNF-a into the brain. As early as 2h after the TNF-a challenge, MCP-1 mRNA and protein were observed in the liver by Taqman RT-PCR and ELISA. The serum MCP-1 level was also elevated between 2 and 4 h, which was consistent with maximal mobilisation of leukocytes into the blood. Monocyte recruitment was most marked in the liver after 6 h, but was delayed in the brain until 24 h. Elevated hepaticand serum chemokines are implicated in the control of leukocytosis and leukocyte recruitment to the brain and liver, since dexamethasone pretreatment attenuated the hepatic MCP-1 response, modulated leukocyte mobilisation and reduced monocyte entry not only to the brain but also to the liver. Thus hepatic chemokine production controls and amplifies the CNS response to inflammation by controlling the rate, timing, magnitude and composition of leukocyte recruitment to the damaged brain
Two new Bent-toed Geckos of the Cyrtodactylus pulchellus complex from Peninsular Malaysia and multiple instances of convergent adaptation to limestone forest ecosystems
No full textGrismer, L. Lee, Wood, Perry L., Anuar, Shahrul, Grismer, Marta S., Quah, Evan S. H., Murdoch, Matthew L., Muin, Mohd Abdul, Davis, Hayden R., Aguilar, César, Klabacka, Randy, Cobos, Anthony J., Aowphol, Anchalee, Sites, Jack W. (2016): Two new Bent-toed Geckos of the Cyrtodactylus pulchellus complex from Peninsular Malaysia and multiple instances of convergent adaptation to limestone forest ecosystems. Zootaxa 4105 (5): 401-429, DOI: 10.11646/zootaxa.4105.5.
Protest and resistance in the crime writing of Anne Perry
No full textAbstract Anne Perry writes to re-write herself, to protest women's condition, and to explore and re-imagine her own. This paper will examine how the essentialising label of evil became the established reading of Anne Perry (Juliet Hulme) and Pauline Parker and their crime, and how as a result of this vilification, protest and resistance became key provocations for Perry's adult writing. It will show how Perry uses her fiction to protest women's position generally, and as a means of resisting the label of evil and re-writing self. It will examine her crime detective fiction writing following the development of both her Pitt and Monk series, and will explore themes in her work of forgiveness and redemption through compassion and positive endeavour. It will show how Perry's books have helped create a different ending. They are a form of redemption in themselves: a re-configuring for Perry of the construction of evil to that of writer and published author
- …
