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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The synthesis of IgE is regulated by cytokines secreted from T-helper cells. The studies on cytokine secretion by peripheral blood mononuclear cells (PBMC) upon stimulation with antigen or allergen are ditficult due to low levels of cytokines, especially of inlerieukin-4 (IL-4).Objective ln this study we tried lo establish a culture system, which could enable the measurement of the cytokine profiles in specifically activated cultures.Methods Three methods to potentiate cytokine secretion were evaluated: PBMC from bee venom or house dust mite (Dermatophagoides pteronyssinus) allergic patients as well as normal subjects were stimulated either with the major bee venom allergen phosphoiipase A2 (PLA) or with the major D. pteronyssinus allergen (Der p 1) or with the control antigens tetanus toxoid (TT) and purified protein derivate (PPD). After 7 days of culture the cells were restimulated either wilh pkistie bound 0KT3 F(ab)2 monoclonal antibodies (MoAbs), with the appropriate antigen + antigen presenting cells or with IL-2. The secretion of cylokines (IL-4, IFNγ) was measured after restimulation of the cultures (day 8).Results While OKT3 F(ab)2 was unable lo activate resting T cells, it could restimulate preactivaled cells. Restimulalion with OKT3 F(ab)2 induced higher IL-4 and IFN7 secretion than restimulation with IL-2 or antigen. TT and PLA stimulated a similar cytokine secretion prolile in normal and PLA allergic subjects with substantial levels of both lL-4 and IFNγ. In contrast, PPD induced virtually only IFNγ secretion. Der p 1 stimulated mainly IL-4 seerclion but also IFNγ production in some mite allergic palienis.Conclusion We have established a cell culture system, which combines antigen specificity with a strong cytokine inducing signial provided by anti-CD3 MoAbs. TH-1 and TH-2 characteristic cytokine patterns can be observed in short-term PBMC cultures already after 8 days of culture.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 45 (1989), S. 521-526 
    ISSN: 1420-9071
    Keywords: IFN-γ ; B-lymphocytes ; lymphokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Interferon-gamma (IFN-γ) exerts a broad spectrum of activities which affect the responses of mature B-cells. It strongly inhibits B-cell activation, acts as a B-cell growth factor (BCGF), and also induces final differentiation to immunoglobulin (Ig) production. IFN-γ is deeply involved in the differential control of isotype expression, as it enhances IgG2a production and suppresses both IgG1 and IgE production. Although it is now possible to draw a general scheme of the effects of IFN-γ on B-cells, a number of paradoxical results still exist in the field. In this manuscript, different experimental systems are analyzed in an attempt to explain these apparent paradoxes.
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  • 3
    ISSN: 1432-0851
    Keywords: alpha interferon ; immunomodulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung T-Lymphozyten von 21 unbehandelten Patienten mit akuter Bruzellose wurden auf ihre Proliferations-antwort auf polyklonale Mitogene untersucht. Auf Pflanzenlektine und anti-CD3-monoklonale Antikörper reagierten die gereinigten T-Lymphozyten dieser Patienten mit einer im Vergleich zu T-Lymphozyten von 21 gesunden Kontrollpersonen verminderten Proliferations-Antwort (p〈0,05). Dieser Defekt konnte durch die exogene Gabe von Interleukin-2 und Tumornekrosefaktor alpha oder beta zum Kulturmedium nicht ausgeglichen werden. Nach Antibiotikatherapie näherte sich die T-Lymphozyten-Proliferationsantwort der Patienten an die der gesunden Kontrollpersonen (p〉0,05) an; sie war gegenüber der Phase vor Therapie signifikant gesteigert (p〈0,05). Aus diesen Befunden ist auf einen Defekt in der Proliferationsantwort der T-Lymphozyten auf mitogene Membransignale zu schließen, der verschwindet, wenn die Patienten nach Antibiotikatherapie geheilt sind.
    Notes: Summary T lymphocytes from 21 untreated patients with acute brucellosis were tested for their proliferative response to polyclonal mitogens. The purified T lymphocytes from these patients showed a defective proliferative response to plant lectins and anti CD3 monoclonal antibodies with respect to the response observed in T lymphocytes from 21 healthy controls (p〈0.05). This defective proliferative response was not corrected by the exogenous addition of interleukin-2 or tumor necrosis factors alpha or beta to the culture medium. After antibiotic therapy, the proliferative response to the mitogens in T lymphocytes was found to be similar to that of the healthy controls (p〉0.05), and significantly higher than that found before treatment (p〈0.05). It was concluded that T lymphocytes from acute brucellosis patients have a defective proliferative response to membrane mitogenic signals, which disappears when the patients are cured after antibiotic treatment.
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  • 5
    Publication Date: 2016-09-17
    Description: Gene expression measurements represent the most important source of biological data used to unveil the interaction and functionality of genes. In this regard, several data mining and machine learning algorithms have been proposed that require, in a number of cases, some kind of data discretization to perform the inference. Selection of an appropriate discretization process has a major impact on the design and outcome of the inference algorithms, as there are a number of relevant issues that need to be considered. This study presents a revision of the current state-of-the-art discretization techniques, together with the key subjects that need to be considered when designing or selecting a discretization approach for gene expression data.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
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  • 6
    Publication Date: 2016-08-23
    Description: When SUCNR1 /GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production of IL-1β during antigen-induced arthritis. Succinate is abundant in synovial fluids from rheumatoid arthritis (RA) patients, and these fluids elicit IL-1β release from macrophages in a GPR91-dependent manner. Together, we reveal a GPR91/succinate-dependent feed-forward loop of macrophage activation and propose GPR91 antagonists as novel therapeutic principles to treat RA.
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
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  • 7
    Publication Date: 2013-12-21
    Description: The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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