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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018); 20181023-20181026; Berlin; DOCPT16-1241 /20181106/
    Publication Date: 2018-11-07
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: RECEPTOR ; EXPRESSION ; Germany ; DISTINCT ; CUTTING EDGE ; INFECTION ; ANTIGEN ; DENDRITIC CELLS ; T cells ; T-CELLS ; cytokines ; TRANSCRIPTION FACTORS ; CROSS-PRESENTATION ; GENE INDUCTION ; dendritic cell ; CELL BIOLOGY ; sepsis ; IFN-ALPHA/BETA ; RECEPTOR 4 ; splenic macrophages ; type I IFN
    Abstract: Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis.
    Type of Publication: Journal article published
    PubMed ID: 22036947
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  • 3
    Keywords: DENDRITIC CELLS ; ESCHERICHIA-COLI ; NECROSIS-FACTOR-ALPHA ; EPITHELIAL-CELLS ; IMMUNE-RESPONSE ; MATRIX METALLOPROTEINASES ; CHEMOKINE RECEPTORS ; URINARY-TRACT-INFECTION ; BACTERIAL-INFECTION ; BASEMENT-MEMBRANES
    Abstract: The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C(-) macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C(+) macrophages. Such Ly6C(+) macrophages played a previously undescribed helper role: once recruited to the site of infection, they produced the cytokine TNF, which caused Ly6C(-) macrophages to secrete CXCL2. This chemokine activated matrix metalloproteinase-9 in neutrophils, allowing their entry into the uroepithelium to combat the bacteria. In summary, the sentinel macrophages elicit the powerful antibacterial functions of neutrophils only after confirmation by the helper macrophages, reminiscent of the licensing role of helper T cells in antiviral adaptive immunity. These findings identify helper macrophages and TNF as critical regulators in innate immunity against bacterial infections in epithelia.
    Type of Publication: Journal article published
    PubMed ID: 24485454
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  • 4
    ISSN: 1432-0533
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zwei Beobachtungen von Torsionspasmus begleitet von Choreoathetose werden mitgeteilt. Bei beiden Fällen handelt es sich um eine Affektion, die im Kindesalter beginnt, sich langsam und protrahiert entwickelt und anatomisch durch eine reine Pallidumatrophie ähnlich den vonvan Bogaert beschriebenen Fällen charakterisiert ist. Der Befund von Lafora-Körperchen im äußeren Pallidumglied stellt ein besonderes Merkmal dar. Dieses erklärt sich vielleicht durch die ungewöhnlichen lange Entwicklung und erlaubt, die beiden Beobachtungen mit der Myoklonuskörperkrankheit nachSeitelberger zu vergleichen und ein Störung des Kohlenhydratstoffwechsels vermutet wird.
    Notes: Résumé Deux observations de spasme de torsion accompagné de choréo-athétose sont rapportées. Dans les deux cas, il s'agit d'une affection débutant dans l'enfance, à évolution lente et prolongée, et caractérisée anatomiquement par une atrophie pallidale pure semblable à celles rapportées parvan Bogaert. La présence de corps de Lafora dans la partie externe du globus pallidus lui confère un caractère original. Ce dernier s'explique peut-être par la longueur inhabituelle de l'évolution et permet de comparer ces deux observations à la «Maladie à inclusions myocloniques» postulée parSeitelberger, et pour laquelle un dérèglement du métabolisme des hydrates de carbone est envisagé.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2018-05-18
    Description: Background Urinary platinum (Pt) excretion is a reliable biomarker for occupational Pt exposure and has been previously reported for precious metals refinery workers in Europe but not for South Africa, the world’s largest producer of Pt. Objective This study aimed to quantify the urinary Pt excretion of South African precious metals refinery workers. Methods Spot urine samples were collected from 40 workers (directly and indirectly exposed to Pt) at two South African precious metals refineries on three consecutive mornings prior to their shifts. Urine samples were analysed for Pt using inductively coupled plasma-mass spectrometry and were corrected for creatinine content. Results The urinary Pt excretion of workers did not differ significantly between sampling days. Urinary Pt excretions ranged from 〈0.1 to 3.0 µg Pt/g creatinine with a geometric mean of 0.21 µg Pt/g creatinine (95% CI 0.17 to 0.26 µg Pt/g creatinine). The work area (P=0.0006; 2 =0.567) and the number of years workers were employed at the refineries (P=0.003; 2 =0.261) influenced their urinary Pt excretion according to effect size analyses. Directly exposed workers had significantly higher urinary Pt excretion compared with indirectly exposed workers (P=0.007). Conclusion The urinary Pt excretion of South African precious metals refinery workers reported in this study is comparable with that of seven other studies conducted in precious metals refineries and automotive catalyst plants in Europe. The Pt body burden of workers is predominantly determined by their work area, years of employment in the refineries and whether they are directly or indirectly exposed to Pt.
    Print ISSN: 1351-0711
    Electronic ISSN: 1470-7926
    Topics: Medicine
    Published by BMJ Publishing Group
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