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51.
Endogenous signals released from necrotic cells augment inflammatory responses to bacterial endotoxin 总被引:4,自引:0,他引:4
El Mezayen R El Gazzar M Seeds MC McCall CE Dreskin SC Nicolls MR 《Immunology letters》2007,111(1):36-44
Stressed cells undergoing necrosis release molecules that acts as endogenous danger signals to alert and activate innate immune cells. Both HMGB1 and HSP70 are induced in activated monocytes/macrophages and also are released from stressed or injured cells. We investigated whether HMGB1 and HSP70 released from necrotic monocytes/macrophages, can act as danger signals to mediate proinflammatory cytokine responses to bacterial endotoxin or lipopolysaccharide (LPS). We show that cell lysate, obtained from necrotic cells directly stimulates the proinflammatory cytokine and chemokine responses in human monocyte/macrophage cell line, THP-1, as revealed by the induction of TNF-alpha, IL-6 and IL-8 mRNA expression and protein production. In the presence of LPS, necrotic cell lysate induced a more robust increase in all three proteins. We found that HMGB1 and HSP70 were indeed present in the necrotic cell lysate and were responsible for the significant induction of the proinflammatory cytokine expression, as neutralization with antibodies against both proteins blocked the increase in the cytokine production seen after incubating LPS-stimulated cells with the necrotic cell lysate. We also found that the newly identified triggering receptor expressed on myeloid cells-1 (TREM-1) was involved in mediating the HMGB1- and HSP70-induced cytokine production. Blocking TREM-1 on THP-1 cells with a recombinant chimera prevented the increase in cytokine production, while simultaneous blocking of TLR4 and TREM-1 completely abolished the proinflammatory response, suggesting that TREM-1 synergizes with TLR4 to mediate the effects of such signals from necrotic cells. In addition, blocking HMGB1 or HSP70 simultaneously with TREM-1 did not decrease the cytokine level further, confirming the involvement of TREM-1 in mediating the effect of HMGB1 and HSP70. Although the interaction of HMGB1 and HSP70 with TREM-1 induced I kappa B alpha and p38 expression, both of which are required for the inflammatory cytokine expression, blockade of TREM-1 did not affect I kappa B alpha expression but markedly reduced p38 activation, as revealed by Western blot analysis. Together, these results demonstrate that HMGB1 and HSP70 released from necrotic cells function as endogenous danger signals to augment the proinflammatory responses in monocytes/macrophage and that TREM-1 relays such signals to the cytokine expression cascade. This mechanism may contribute to the amplification and persistence of the inflammatory response to bacterial infection. 相似文献
52.
Online information for parents caring for their premature baby at home: A focus group study and systematic web search
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Fiona Alderdice BSSc PhD Phyl Gargan BSc MSc Emma McCall BSc MSc Linda Franck RN PhD 《Health expectations》2018,21(4):741-751
Background
Online resources are a source of information for parents of premature babies when their baby is discharged from hospital.Objectives
To explore what topics parents deemed important after returning home from hospital with their premature baby and to evaluate the quality of existing websites that provide information for parents post‐discharge.Methods
In stage 1, 23 parents living in Northern Ireland participated in three focus groups and shared their information and support needs following the discharge of their infant(s). In stage 2, a World Wide Web (WWW) search was conducted using Google, Yahoo and Bing search engines. Websites meeting pre‐specified inclusion criteria were reviewed using two website assessment tools and by calculating a readability score. Website content was compared to the topics identified by parents in the focus groups.Results
Five overarching topics were identified across the three focus groups: life at home after neonatal care, taking care of our family, taking care of our premature baby, baby's growth and development and help with getting support and advice. Twenty‐nine sites were identified that met the systematic web search inclusion criteria. Fifteen (52%) covered all five topics identified by parents to some extent and 9 (31%) provided current, accurate and relevant information based on the assessment criteria.Conclusion
Parents reported the need for information and support post‐discharge from hospital. This was not always available to them, and relevant online resources were of varying quality. Listening to parents needs and preferences can facilitate the development of high‐quality, evidence‐based, parent‐centred resources. 相似文献53.
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Jared F. Cook MA Deborah F. Hill MA Beverly M. Snively PhD Niki Boggs BA Cynthia K. Suerken MS Ihtsham Haq MD Mark Stacy MD W. Vaughn McCall MD MS Laurie J. Ozelius PhD Kathleen J. Sweadner PhD Allison Brashear MD 《Movement disorders》2014,29(3):344-350
Rapid‐onset dystonia‐parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation‐negative controls. We studied 22 familial RDP patients, 3 non‐motor‐manifesting mutation‐positive family members, 29 mutation‐negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia‐parkinsonism. The affected RDP patients performed more poorly, on average, than mutation‐negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P ≤ 0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP. © 2014 International Parkinson and Movement Disorder Society 相似文献
57.
Sewage‐based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC‐MS/MS
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Juliet Kinyua Adrian Covaci Walid Maho Ann‐Kathrin McCall Hugo Neels Alexander L. N. van Nuijs 《Drug testing and analysis》2015,7(9):812-818
Sewage‐based epidemiology (SBE) employs the analysis of sewage to detect and quantify drug use within a community. While SBE has been applied repeatedly for the estimation of classical illicit drugs, only few studies investigated new psychoactive substances (NPS). These compounds mimic effects of illicit drugs by introducing slight modifications to chemical structures of controlled illicit drugs. We describe the optimization, validation, and application of an analytical method using liquid chromatography coupled to positive electrospray tandem mass spectrometry (LC‐ESI‐MS/MS) for the determination of seven NPS in sewage: methoxetamine (MXE), butylone, ethylone, methylone, methiopropamine (MPA), 4‐methoxymethamphetamine (PMMA), and 4‐methoxyamphetamine (PMA). Sample preparation was performed using solid‐phase extraction (SPE) with Oasis MCX cartridges. The LC separation was done with a HILIC (150 x 3 mm, 5 µm) column which ensured good resolution of the analytes with a total run time of 19 min. The lower limit of quantification (LLOQ) was between 0.5 and 5 ng/L for all compounds. The method was validated by evaluating the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recoveries and matrix effects. The method was applied on sewage samples collected from sewage treatment plants in Belgium and Switzerland in which all investigated compounds were detected, except MPA and PMA. Furthermore, a consistent presence of MXE has been observed in most of the sewage samples at levels higher than LLOQ. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
58.
Role of arachidonic acid in stimulation of hexose transport by human polymorphonuclear leukocytes 总被引:1,自引:0,他引:1
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David A. Bass Joseph T. O''Flaherty Pamela Szejda Lawrence R. DeChatelet Charles E. McCall 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(9):5125-5129
Whereas insulin does not stimulate hexose transport in polymorphonuclear leukocytes, we recently reported that C5a causes the leukocytes to take up 2-[3H]deoxyglucose. We now find that fMet-Leu-Phe, in a concentration-related manner with an EC50 (concentration producing 50% of stimulatory activity) of 1.2 nM, causes a 5.5-fold stimulation of deoxyglucose uptake. Moreover, arachidonic acid (5,8,11,14-eicosatetraenoic acid) similarly stimulated deoxyglucose uptake with an EC50 of 0.6 μM. Stimulation by arachidonic acid exhibited structural specificity; five structural analogues of arachidonic acid, including arachidonyl alcohol, 8,11,14-eicosatrienoic acid, 11,14,17-eicosatrienoic acid, 5,8,11,14-eicosatetraynoic acid, and arachidic acid, did not stimulate deoxyglucose uptake. Release and metabolism of arachidonic acid may also be involved in the stimulation of deoxyglucose uptake by fMet-Leu-Phe. Inhibitors of arachidonic acid metabolism (5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, indomethacin, aspirin, and benzylimidazole) caused parallel changes in the responses to both arachidonic acid and fMet-Leu-Phe. Stimulation of deoxyglucose uptake of polymorphonuclear leukocytes by chemotactic factors or arachidonic acid had the characteristics of carrier-facilitated hexose transport. The response was saturable with increasing concentrations of stimulant or substrate (deoxyglucose). It was stereospecific (inhibited by D-glucose but not by L-glucose) and was inhibited in resting and stimulated cells by 5 μg of cytochalasin B per ml. It was separable from the stimulation of oxidative metabolism; it occurred normally in polymorphonuclear leukocytes from a patient with chronic granulomatous disease (these are incapable of an oxidative metabolic response to membrane stimuli). Thus, stimulation of polymorphonuclear leukocytes is associated with enhanced hexose transport. Moreover, carrier-facilitated hexose transport and arachidonic acid metabolism may be linked, at least in these leukocytes: arachidonic acid mimies the stimulatory effects of chemotactic factors, and blockade of arachidonic acid metabolism inhibits the stimulation of hexose transport by these agents. 相似文献
59.
Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection 总被引:1,自引:0,他引:1
Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E. 相似文献