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  • 1
    In: Intensive Care Medicine, Springer Science and Business Media LLC, Vol. 29, No. 6 ( 2003-6), p. 915-922
    Type of Medium: Online Resource
    ISSN: 0342-4642 , 1432-1238
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2003
    detail.hit.zdb_id: 1459201-0
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  • 2
    In: Molecular Pharmacology, American Society for Pharmacology & Experimental Therapeutics (ASPET), Vol. 62, No. 2 ( 2002-08-01), p. 379-388
    Type of Medium: Online Resource
    ISSN: 0026-895X , 1521-0111
    Language: English
    Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
    Publication Date: 2002
    detail.hit.zdb_id: 1475030-2
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 165, No. 10 ( 2000-11-15), p. 5932-5937
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 165, No. 10 ( 2000-11-15), p. 5932-5937
    Abstract: Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p ≤ 0.01) and incidence (p ≤ 0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p ≤ 0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-α and IL-1β in adult life than control rats (p & lt; 0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-γ (p & lt; 0.01) and TNF-β (p & lt; 0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
    detail.hit.zdb_id: 1475085-5
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  • 4
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 171, No. 11 ( 2003-12-01), p. 6128-6134
    Abstract: Directed migration of polymorphonuclear neutrophils (PMN) is required for adequate host defense against invading organisms and leukotriene B4 (LTB4) is one of the most potent PMN chemoattractants. LTB4 exerts its action via binding to BLT1, a G protein-coupled receptor. G protein-coupled receptors are phosphorylated by G protein-coupled receptor kinases (GRK) in an agonist-dependent manner, resulting in receptor desensitization. Recently, it has been shown that the human BLT1 is a substrate for GRK6. To investigate the physiological importance of GRK6 for inflammation and LTB4 signaling in PMN, we used GRK6-deficient mice. The acute inflammatory response (ear swelling and influx of PMN into the ear) after topical application of arachidonic acid was significantly increased in GRK6−/− mice. In vitro, GRK6−/− PMN showed increased chemokinetic and chemotactic responses to LTB4. GRK6−/− PMN respond to LTB4 with a prolonged increase in intracellular calcium and prolonged actin polymerization, suggesting impaired LTB4 receptor desensitization in the absence of GRK6. However, pre-exposure to LTB4 renders both GRK6−/− as well as wild-type PMN refractory to restimulation with LTB4, indicating that the presence of GRK6 is not required for this process to occur. In conclusion, GRK6 deficiency leads to prolonged BLT1 signaling and increased neutrophil migration.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
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    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2003
    detail.hit.zdb_id: 1475085-5
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2003
    In:  The Lancet Vol. 361, No. 9369 ( 2003-05), p. 1654-
    In: The Lancet, Elsevier BV, Vol. 361, No. 9369 ( 2003-05), p. 1654-
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2004
    In:  Intensive Care Medicine Vol. 30, No. 10 ( 2004-10), p. 1865-1872
    In: Intensive Care Medicine, Springer Science and Business Media LLC, Vol. 30, No. 10 ( 2004-10), p. 1865-1872
    Type of Medium: Online Resource
    ISSN: 0342-4642 , 1432-1238
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 1459201-0
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  • 7
    In: Psychotherapy and Psychosomatics, S. Karger AG, Vol. 70, No. 6 ( 2001), p. 307-318
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Previous studies of cancer patients investigated the effect of psychological treatment on basal endocrine and immune values. Using a randomized experiment, we explored the effect of a 13-week experiential-existential group psychotherapy (EEGP) program on the reactivity to a speech task in breast cancer patients. We explored whether changes in cardiovascular and immune reactivity to a speech task over the 3-month period correlated with changes in psychological distress and emotional expression. 〈 i 〉 Methods: 〈 /i 〉 Patients who had been treated for early-stage breast cancer and who were diagnosed as having either positive axillary lymph nodes or distant metastases were randomly assigned to either EEGP or a waiting list control (WLC) condition. We continuously recorded heart rate (HR), diastolic (DBP) and systolic blood pressure (SBP) in response to the speech task before and after treatment. We also measured lymphocyte proliferation to pokeweed (PWM) and phytohemagglutinin (PHA), and natural killer cell activity (NKCA) as well as peripheral blood lymphocyte distributions in blood samples that were drawn before, during and after the speech task. 〈 i 〉 Results: 〈 /i 〉 Patients in EEGP had smaller increases in natural killer (NK) cells induced by the speech task after treatment versus task-induced values observed at study entry and greater than pre-/posttreatment changes seen in patients randomized to the WLC. A similar pattern emerged with respect to NKCA over the intervention period, which was independent of the changes in NK cells. There were no differences between patients assigned to EEGP and WLC in HR, DBP and SBP responses as well as in changes in PWM- and PHA-induced lymphocyte proliferation in response to the speech task measured before and after the 3-month intervention period. Individual differences in pre-/posttreatment increases in emotional expression but not in psychological distress were significantly associated with smaller changes in the number and function of NK cells over the 3-month period. 〈 i 〉 Conclusions: 〈 /i 〉 These findings may indicate that emotional expression during EEGP may render breast cancer patients more comfortable expressing their emotional responses to the speech challenge, which, in turn, results in smaller stress-induced changes in NK cells and function.
    Type of Medium: Online Resource
    ISSN: 0033-3190 , 1423-0348
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    Language: English
    Publisher: S. Karger AG
    Publication Date: 2001
    detail.hit.zdb_id: 1472321-9
    SSG: 5,2
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    American Academy of Pediatrics (AAP) ; 2001
    In:  Pediatrics Vol. 107, No. 3 ( 2001-03-01), p. e35-e35
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 107, No. 3 ( 2001-03-01), p. e35-e35
    Abstract: To examine psychosocial problems and adaptation of adolescent girls with chronic fatigue syndrome (CFS). Methodology. Thirty-six adolescent girls with CFS (mean age: 15.2 years; mean syndrome duration: 19.7 months) who fulfilled the criteria of the Centers for Disease Control and Prevention were examined by interviews regarding premorbid problems and by questionnaires regarding psychosocial functioning and distress, psychological attitudes, and coping resources. Data were compared with normative data. Results. Of the adolescents, 86.1% reported 1 or more premorbid problems (58.3% physical, 38.9% psychological, and 52.8% familial). Normal adjustment was reported for psychosocial self-esteem, social abilities, and attentional abilities. High adjustment to adult social standards of behavior was found, but low perceived competence in specific adolescent domains, such as athletic ability, romance, and participation in recreational activities. The girls reported predominantly internalizing problems. Normal achievement motivation, no debilitating fear of failure, and high internal locus of control were observed. Palliative reaction patterns and optimism were predominantly used as coping strategies. Conclusions. The large number of premorbid problems suggests a possible contributing factor to the onset of the syndrome, although there were no reference data of healthy adolescents. In distinct domains of psychosocial adjustment, the adolescent girls with CFS showed strengths such as adequate self-esteem and scholastic and social abilities, and weaknesses such as low competence in adolescent-specific tasks and internalizing distress, which may partly be explained by syndrome-specific somatic complaints. The use of optimistic and palliative reaction patterns as coping strategies in this patient group indicates that the patients with CFS seem to retain an active and positive outlook on life, which may result in a rather adequate psychological adaptation to the syndrome, but also in maintenance of the syndrome by exceeding the physical limits brought about by the CFS. Our results on adjustment and coping strategies may be helpful to implement (individual) rehabilitation programs.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2001
    detail.hit.zdb_id: 1477004-0
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2004
    In:  Journal of Leukocyte Biology Vol. 75, No. 5 ( 2004-05-01), p. 901-909
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 75, No. 5 ( 2004-05-01), p. 901-909
    Abstract: Chemokine receptors belong to the family of G-protein-coupled receptors (GPCR). Phosphorylation of GPCR by GPCR kinases (GRKs) is considered to play an important role in desensitization of these receptors. We have recently shown in patients with rheumatoid arthritis that the level of GRK2 in lymphocytes is reduced by ∼50%. However, the physiological relevance of reduced GRK2 levels in lymphocytes is not known. Here, we investigated whether reduced GRK2 expression changes the chemotactic response of T cells to the chemokines CCL3, CCL4, and CCL5. Activated T cells from GRK2+/− mice, which have a 50% reduction in GRK2 protein levels, showed a significant 40% increase in chemotaxis toward the CCR5 ligand CCL4. In addition, chemotaxis toward the CCR1 and CCR5 ligands CCL3 and CCL5 was also increased. Binding of CCL4 to activated T cells from GRK2+/− and wild-type (WT) mice was similar, but agonist-induced CCR5 phosphorylation was attenuated in GRK2+/− cells. Moreover, the calcium response and phosphorylation of protein kinase B and extracellular-regulated kinase in response to CCL4 were significantly increased in GRK2+/− T cells, showing that signaling is increased when the level of GRK2 is reduced. GRK2+/− and WT cells do become refractory to restimulation with CCL4. In conclusion, a 50% decrease in T cell GRK2 expression results in increased responsiveness to CCL3, CCL4, and CCL5, suggesting that the 50% reduction in lymphocyte GRK2 level as observed during inflammation can have functional consequences for the response of these cells to chemokines.
    Type of Medium: Online Resource
    ISSN: 0741-5400 , 1938-3673
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
    detail.hit.zdb_id: 2026833-6
    SSG: 12
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  • 10
    In: Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 75, No. 4 ( 2004-04-01), p. 698-704
    Abstract: The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling pathway is thought to play an important role in the induction of neutrophil mobilization from the bone marrow in response to granulocyte-colony stimulating factor (G-CSF) treatment. CXCR4 belongs to the family of G protein-coupled receptors. Multiple members of this receptor family are desensitized by agonist-induced G protein-coupled receptor kinase (GRK)-mediated phosphorylation. Here, we demonstrate that in vitro SDF-1-induced chemotaxis of bone marrow-derived neutrophils from GRK6-deficient mice is significantly enhanced and that desensitization of the calcium response to SDF-1 is impaired in GRK6−/− neutrophils. CXCR4 activation by SDF-1 provides a key retention signal for hematopoietic cells in the bone marrow. It is interesting that we observed that in the absence of GRK6, the G-CSF-induced increase in circulating neutrophils is profoundly impaired. Three days after injection of pegylated-G-CSF, significantly lower numbers of circulating neutrophils were observed in GRK6−/− as compared with wild-type (WT) mice. In addition, early/acute neutrophil mobilization in response to G-CSF (3 h after treatment) was also impaired in GRK6−/− mice. However, blood neutrophil levels in untreated GRK6−/− and WT mice were not different. Moreover, the percentage of neutrophils in the bone marrow after G-CSF treatment was increased to the same extent in WT and GRK6−/− mice, indicating that neutrophil production is normal in the absence of GRK6. However, the increased chemotactic sensitivity of GRK6−/− neutrophils to SDF-1 was retained after G-CSF treatment. In view of these data, we suggest that the impaired G-CSF-induced neutrophil mobilization in the absence of GRK6 may be a result of enhanced CXCR4-mediated retention of PMN in the bone marrow.
    Type of Medium: Online Resource
    ISSN: 0741-5400 , 1938-3673
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
    detail.hit.zdb_id: 2026833-6
    SSG: 12
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