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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 257-264 
    ISSN: 1432-1440
    Keywords: Asthma ; Bronchitis ; Leukotrienes ; HPLC ; RIA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of lipoxygenase products was studied in children suffering from chronic diseases of the lung. Leukotrienes C4, D4, E4 and B4 were measured by high performance liquid chromatography (HPLC) and a specific radioimmunoassay (RIA) for C4. Elevated levels (up to 40 ng/ml), especially for leukotriene E4, were found in plasma of asthmatic and bronchitic patients (leukotriene C4 concentrations varied between 0.05 and 40 ng/ml, mean 4.9±7.8 ng/ml). In healthy donors the concentrations were below the detection limits of HPLC, leukotriene C4 ranging between 5±4 ng/ml (RIA data). The conversion of leukotriene C4 to D4 and E4 was observed by incubating the samples with synthetic leukotriene C4. The half-life of leukotriene C4 in plasma varied greatly, ranging from 〈12 min to 72 min (mean 39±16 min). Bronchial lavages yielded leukotriene C4 concentrations of 0.2 to 7 ng. Leukotriene E4 was detected in 10 of 41 cases. Conversion of leukotriene C4 did not occur in 50% of all cases, but was regularly observed in putrid lavages. These data suggest that leukotrienes play an important role in allergic and infectious lung diseases.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 25 (1987), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human polymorphonuclear granulocytes (PMN) metabolize exogenous [3H]leukotriene B4 (LTB4) into 20-hydroxy- and 20-carboxy-[3H]LTB4. The conversion was enhanced at acidic pH values (pH 6.0–7.0). Sonication of purified PMN and subcellular fractionation by differential centrifugation showed that major LTB4-hydroxylase activity was associated with the microsomal fraction (105,000 g pellet). In contrast to intact cells. LTB4-hydroxylase activity within the microsomal fraction revealed optimal activity at neutral pH and was inhibited by a wide range of divalent cations. There was a strict requirement for the presence of suitable electron donors such as NADPH, Heterocyclic nitrogenous bases, such as imidazole and pyridine, inhibited the LTB4, conversion induced by intact PMN as well as by their microsomes. These observations combined with the spectrophotometric analysis (carbon monoxide dithionite-reduced difference spectrum) supported the assumption that LTB4-hydroxylase resembled a cytochrome P-450 enzyme. The LTB4-hydroxylase within human PMN was not identical with the cytochrome P-450 of rat liver; hepatic microsomes only showed minute conversion of LTB4.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 25 (1987), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Polymorphonuclear leucocytes released LTD4-dipeptidase activity in a time-, calcium-, and cell number-dependent fashion. The LTD4-dipeptidase released from polymorphonuclear leucocytes (PMN) by incubation with calcium (0.91 mm) was detectable up to a cell concentration of 1 × 106/ml and increased with higher concentrations. Maximal LTD4-dipeptidase activity within the extracellular environment was detected after 15 min of incubation (2x107/ml) in the presence of 2–4.5 mm calcium or after 30 min, when stimulation was carried out with 0.91 mm calcium. The activity of the released LTD4-dipeptidase was modulated by various metal ions and other compounds. The addition of Mn2+ Co2+, and Zn2+ (final concentration 1 mm) enhanced the LTD4-dipeptidase activity, while Cu2+ led to a complete inhibition. In the absence of exogenoas calcium EDTA inhibited LTD4-dipeptidase. Calcium up to a concentration of 5 and 10mm decreased the dipeptidase activity. The LTD4-dipeptidase is not affected by bestatin, leupeptin. or N-ethyl-maleinimide (NEM). The Km of LTD4-dipeptidase for LTD4 was 0.95±0.2μm and vmax was 737.5±112.5 pmol/min × mg protein (n = 3±SEM). The highest LTD4dipeptidase activity was obtained at physiological pH values. LTD4-dipeptidase activity can also be released from other cell types, but the enzyme activity from human PMN exceeded that of other cells (e.g. human lymphocytes/monocytes and basophils (LMB) and human lung cell suspension).
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 43 (1996), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In vitro cultured cells derived from human bone marrow stimulated with macrophage-colony stimulating factor (M-CSF) or granulocyte-macrophage-colony stimulating factor (GM-CSF) were investigated for their immunophenotypic surface characteristics by flow cytometry. Approximately 80–90% of the cells showed morphological and histochemical features of macrophages and bore CD11a, CD11b, CD11c, CD14, CD29, CD32, CD33, CD44, CD45, CD54, CD64, CD71, HLA-DR antigen. The expression of CD4, CD25 and CD45RO were detected only in low density. Bone marrow-derived macrophages were negative for CD8, CD45RA, CD16 and CD23. Functionally, macrophages were able to phagocytose opsonized Escherichia coli, but no oxidative bursts were induced either by fmlp or by opsonized bacteria. Cell surface phenotyping revealed a CD pattern very similar to monocyte-derived phagocytes, and was partially distinct from resident stromal macrophages.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 219 (1975), S. 237-237 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-0385
    Keywords: Schlüsselwörter: Interleukin-12 ; Polytrauma ; Thoraxtrauma ; Immunregulation. ; Keywords: Interleukin-12 ; Polytrauma ; Thoraxtrauma ; Immune regulation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract. Introduction: Interleukin-12-p70 (IL-12-p70) is a potent immunoregulatory cytokine composed of a heavy chain (p40) and a light chain (p35). Contradicting results have been reported with regard to leukocyte release and systemic concentration of IL-12 after polytrauma. Methods: We daily analyzed systemic concentrations of IL-12 in polytrauma patients (n = 37, mean ISS 33.9) in comparison to healthy donor values during intensive care course by ELISA. Patients were divided according to their mean IL-12 levels into those with elevated IL-12 (group 1, n = 7), those with decreased IL-12 (group 2, n = 4) and those with IL-12 in the normal range (group 3, n = 26). Results: Patients in group 1 revealed elevated levels of IL-12 up to p70 〉 1000 pg/ml and p40 〉 2500 pg/ml. The common clinical feature of group 1 was a thorax trauma in combination with pneumonia (85 % survivors). Patients with single thorax trauma or pneumonia without thorax trauma (group 3) showed normal IL-12 values. Patients with decreased IL-12 levels revealed also a thorax trauma and pneumonia but all patients succumbed. The groups significantly differ in their stay in the intensive care unit, in TISS, in MODS score and in respiratory ratio, but not in ISS, mean CRP values and leukocyte counts. Correlation analysis revealed no significant relation between systemically altered IL-12 values and clinical parameters, with the exception of a negative correlation of p70 and ISS (r = –0.785) or MODS score (r = –0.314) in group 1. Conclusions: After major injuries there is no overall suppression of IL-12 formation. Patients with normal or elevated IL-12 levels belong mainly to the survivors, whereas patients with decreased IL-12 levels are at high risk of succumbing to multi-organ failure.
    Notes: Zusammenfassung. Einleitung: IL-12 (p70) ist ein heterodimeres Cytokin, das aus einer leichten Aminosäurekette (p35) und einer schweren Kette (p40) besteht. Die Rolle von IL-12 in der posttraumatisch erworbenen Immundysregulation ist bezüglich der systemischer Konzentrationen und der Freisetzung aus peripheren Leukocyten widersprüchlich. Methoden: Plasma-Spiegel von IL-12 wurden täglich bei 37 Polytrauma-Patienten (mittlerer ISS 33,9) während des intensiv-stationären Aufenthalts im Vergleich zu gesunden Probanden mittels ELISA gemessen. Die Patienten wurden hinsichtlich der mittleren IL-12-Spiegel als Patienten mit erhöhtem IL-12 (Gruppe 1, n = 7), erniedrigtem IL-12 (Gruppe 2, n = 4) oder IL-12 im Normbereich (Gruppe 3, n = 26) eingeteilt. Ergebnisse: Patienten der Gruppe 1 hatten erhöhte IL-12 Spiegel (max. p70 〉 1000 pg/ml, p40 〉 2500 pg/ml). Als klinische Gemeinsamkeit fand sich bei Patienten der Gruppe 1 (85 % Überlebende) stets ein beatmungspflichtiges Thoraxtrauma mit Pneumonie. Patienten mit IL-12 im Normbereich zeigten alleiniges Thoraxtrauma bzw. Pneumonie ohne Thoraxtrauma. Patienten mit erniedrigten IL-12 hatten Thoraxtrauma mit Pneumonie aber verstarben alle. Die Patientengruppen unterschieden sich signifikant hinsichtlich Dauer des intensiv-stationären Aufenthalts, des TISS, des MODS-Score, des respiratorischen Quotienten aber nicht im ISS, den mittleren CRP-Werten und Leukocytenzahlen. Korrelationsanalysen ergaben keinen Zusammenhang von systemisch veränderten IL-12-Spiegeln zu den klinischen Parametern mit Ausnahme einer negativen Korrelation der p70-Spiegel zum ISS (r = –0,785) und MODS-Score (r = -0,314) in Gruppe 1. Schlussfolgerungen: Nach Polytrauma ist nicht von einer allgemeinen Suppression der IL-12 Synthese auszugehen. Patienten mit normalen oder erhöhten IL-12-Spiegeln haben eine gute Prognose, während bei Patienten mit signifikant erniedrigtem IL-12 mit einer erhöhten Mortalität zu rechnen ist.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 383 (1998), S. 460-465 
    ISSN: 1435-2451
    Keywords: Key words Interleukin-10 ; Interleukin-12 ; Polymorphonuclear neutrophil granulocyte ; Trauma ; Staphyloccocus aureus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with severe trauma or polytrauma frequently acquire alterations in immune functions which are correlated to dysbalanced cytokine synthesis. In these settings the role of polymorphonuclear neutrophil granulocytes (PMN) as cytokine-producing cells is less well characterized. The immunosuppressive role of interleukin (IL)-10 is well known, and increased systemic IL-10 levels are related to the severity of injury and to posttraumatic complications. We determined concentrations of IL-10 in culture supernatants of 30 individual PMN fractions isolated from 18 severely traumatized patients (15 polytraumata, Injury Severity Score: 18–41, 3 severely burned patients) admitted to intensive care units. IL-10 was analyzed by ELISA (R&D Systems, Wiesbaden, Germany). PMN were isolated from EDTA-anticoagulated peripheral blood employing a one-step procedure based on a discontinuous double Ficoll gradient. The cells [1×106/ml RPMI 1640 supplemented with 10% fetal calf serum and 25 mM N-(2-hydroxyethyl)-piperazine-N′-(2-ethanesulfonic acid] were stimulated with 0.05% heat-killed Staphylococcus aureus (Pansorbin, Calbiochem-Novabiochem, Bad Soden, Germany) for 24 h using cell culture conditions. Our results show that PMN fractions of traumatized patients produce significantly (P〈0.008) higher amounts of IL-10 (354± 95 pg/ml, n = 30) than normal healthy donor cells (125± 95 pg/ml, n = 7). IL-10 release from PMN fractions exceeded the release from isolated patients' peripheral blood mononuclear cells induced by similar stimulation or by stimulation with toxic shock syndrome toxin-1 (10 ng) and concanavalin A (2 μg). Our results provide evidence that PMN fractions play an active role in the development of posttraumatic immunosuppression by autocrine or paracrine mechanisms, for example, by suppressing one's own antimicrobial activities or determining the development of T-cell responses via their ability to release IL-10.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation 20 (1996), S. 71-85 
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analyzed the effect of the PAF receptor antagonist (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) on human platelet aggregation as well as mediator release. After incubation of human platelet with different concentrations of SM-12502 the cells were subsequently stimulated with either the Ca ionophore A23187, with human thrombin, or with an activator of heterotrimeric G-proteins, sodium fluoride (NaF, in the presence of Al3+). Preincubation of platelets with the PAF receptor antagonist led to an inhibition of 12-lipoxygenase derived 12(S)-HETE and cyclooxygenase derived 12(S)-HHT. Pretreatment of platelets with the PAF receptor antagonist SM-12502 prior to activation with the Ca ionophore A23187 or PAF also inhibited platelet aggregation. Our data clearly indicate an inhibitory effect of the new PAF receptor antagonist SM-12502 on the formation of platelet derived inflammatory mediators of the lipoxygenase pathway as well as of the cyclooxygenase pathway, and furtherone, treatment with the PAF receptor antagonist diminished platelet aggregation after subsequent specific and unspecific activation.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-2576
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analyzed DNA-fragmentation in human polymorphonuclear neutrophil granulocytes (PMNs) from healthy donors after addition of exogenous arachidonic acid (AA) and eicosapentaenoic acid (EPA) by flow cytometry (propidium iodide staining of DNA and DNA strand break detection). The PMNs were incubated from 30 min up to 48 hours in RPMI 1640 which was supplemented with different concentrations of AA or EPA (5–40 μM). In contrast to EPA the addition of AA led to a significant increase in apoptosis up to 67.8% compared to the RPMI-control whereas the addition of EPA led to an inhibition of DNA-fragmentation. When the cells were incubated with MK 886 (1μM, inhibitor of leukotriene biosynthesis) an increase in DNA-fragmentation (up to 63.3%) was observed. Conversely, in the presence of indomethacin (1μM, inhibitor of prostanoid synthesis) an inhibition in DNA-fragmentation (up to 60.9%) occurred. Furthermore, preincubation of PMNs with pentoxifylline (1mM, phosphodiesterase inhibitor) reduced AA-stimulated DNA-fragmentation up to 43.4%. These data provide evidence for the involvement of AA and distinct AA metabolites in the regulation of apoptosis in human PMNs.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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