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  • 2005-2009  (3)
  • Natural Sciences  (3)
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  • 2005-2009  (3)
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  • Natural Sciences  (3)
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  • 1
    Online Resource
    Online Resource
    Wiley ; 2006
    In:  Annals of the New York Academy of Sciences Vol. 1090, No. 1 ( 2006-12), p. 245-252
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1090, No. 1 ( 2006-12), p. 245-252
    Abstract: Abstract:  Trauma causes immediate cytokine release and the systemic inflammatory response syndrome (SIRS), often preceding sepsis and septic shock. Mechanisms may involve P2X7 ion channel activation via adenosine 5′‐triphosphate (ATP) released from surrounding tissue and platelets. A number of single nucleotide polymorphisms (SNPs) influence the nature and magnitude of P2X7‐stimulated cytokine release and apoptosis. In whole blood and isolated mononuclear blood cells (PBMCs) of donors with wild‐type and heterozygous mutated genotypes, we found downregulated IL‐8 and caspase‐3 activation but no reproducible effect on tumor necrosis factor (TNF)‐α and IL‐1β release. IL‐8 and caspase‐3 activation were both influenced by paxilline, an inhibitor of calcium‐activated potassium channels. Confocal laser scanning microscopy demonstrated that calcium signaling is affected by paxilline as well. We propose that blockade of potassium channels may be relevant to attenuate ATP‐induced cytokine responses and apoptosis. The presence of functional SNPs in heterozygous genotypes appears to play a role.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
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  • 2
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1090, No. 1 ( 2006-12), p. 429-444
    Abstract: Abstract:  Microarray expression analysis was performed in patients with major surgical trauma to identify signaling pathways which may be indicative for complicated versus uneventful reconstitution post trauma. In addition to a generalized upregulation of nonspecific stress response genes in all patients, a remarkable number of differences in gene expression patterns were found in individual patients. Some of the differing genes were associated with uncomplicated convalescence such as upregulation of both the ERK5 pathway (MAPK7 [mitogen‐activated protein kinase‐7]) and transcription factors which stimulate hematopoiesis and tissue reconstitution (MEF2, BMP‐2, TNFRSF11A [RANK] , and RUNX‐1). Chemokine genes active in stem cell recruitment from the bone marrow as well as dendritic cell and natural killer (NK) cell maturation (SCYA14 [HCC‐1]), and activators of the lymphoid compartment (TNFRSF7 [CD27] , CD3zeta and perforin [PRF1]) were increased. In contrast, all these transcripts were downregulated in complicated reconstitution and later development of septic shock. Moreover, p38 kinase (MAPK14), S100 molecules, and members of the lipoxygenase pathway were associated with a more eventful outcome. Microarray expression studies are a promising tool for screening and then selecting differentially regulated genes in favorable as compared to complicated reconstitution post trauma.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1090, No. 1 ( 2006-12), p. 168-176
    Abstract: Abstract:  The current comparative investigation analyses markers of inflammation and apoptosis in peripheral blood of intensive care unit (ICU) patients with postoperative/posttraumatic SIRS (systemic inflammatory response syndrome), sepsis, severe sepsis, or septic shock. Inflammatory markers (C‐reactive protein [CRP], cytokines, metalloproteinases [MMPs] ) and soluble FAS‐Ligand (sCD178) were determined in plasma, and apoptosis‐relevant antigens such as active caspase‐3, Bcl‐2, and sCD178 were quantified in whole‐blood cell lysates. These parameters were analyzed daily in 20 postoperative/posttraumatic patients: 2 patients had SIRS, 5 suffered from sepsis (2 died), and 13 had septic shock (5 died). Active caspase‐3, Bcl‐2, and sCD178 were determined by ELISA and by fluorescence‐activated cell sorting (FACS)‐array kits using bead‐assisted flow cytometry. Cytokines and MMPs were quantified by Luminex‐assisted Beadlyte assays. Active caspase‐3 was identified in defined samples of whole‐blood lysates covering, for example, 5/7, 8/18, and 6/11 consecutive days during the patients' stay on the ICU. Also, sCD178 was detected on successive days. Peaks of active caspase‐3 antigen contents in whole blood occurred independently of CRP and inflammatory cytokines such as tumor necrosis factor (TNF)‐α and IL‐6. In addition, high MMPs 1–3, 7–10, and 13 concentrations were detected. Interestingly, active caspase‐3 and cell‐associated sCD178 were either elevated simultaneously or in a close time window. The same was true for Bcl‐2. In conclusion, activation of apoptosis can be determined in whole blood of postoperative/posttraumatic patients by active caspase‐3 and by Bcl‐2. Pro‐ and antiapoptotic effects during sepsis may occur independently of peaks in inflammatory markers. Apoptosis could explain modeling and remodeling of leukocyte subpopulations.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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