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Jenny U. Johansson Nathaniel S. Woodling Qian Wang Maharshi Panchal Xibin Liang Angel Trueba-Saiz Holden D. Brown Siddhita D. Mhatre Taylor Loui Katrin I. Andreasson 《The Journal of clinical investigation》2015,125(1):350-364
Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD. 相似文献
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H. Nilsson J. Johansson K. Svanberg S. Svanberg G. Jori E. Reddi A. Segalla D. Gust A. L. Moore T. A. Moore 《British journal of cancer》1997,76(3):355-364
The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated. 相似文献
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Torsten T. Bauer Joachim Lorenz Klaus-Friedrich Bodmann Friedrich Vogel 《Medizinische Klinik》2005,26(13):355-360
Hintergrund:
Die nosokomiale Pneumonie gehört zu den häufigsten nosokomialen Infektionen und ist die häufigste auf der Intensivstation. Die nosokomiale Pneumonie ist mit einer signifikanten Mortalität und Morbidität assoziiert, und ihr Auftreten verschlechtert die Prognose des Patienten deutlich. Nach der Definition der DRGs auch im deutschen Krankenhaussystem ist die nosokomiale Pneumonie überwiegend Sache des Krankenhauses und kann somit nicht nur das Ergebnis der Patientenbehandlung, sondern auch das finanzielle Ergebnis des Krankenhauses beeinträchtigen. 相似文献9.
Lars von Knorring Béla G. L. Almay Jan Häggendal Folke Johansson Lars Oreland Lennart Wetterberg 《European archives of psychiatry and clinical neuroscience》1986,236(3):131-138
Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet 相似文献
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Dimmeler Stefanie; Tonn Torsten; Seeger Florian; Zeiher Andreas M. 《European heart journal》2007,28(17):2175
It obviously escaped the notion of Egeland and Brinchman thatthe protocols additionally differ with regard to the washingsteps and buffer components used in the 相似文献