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We studied the mechanisms of action leading to the g1ucocorticoid (GC)-induced synthesis of the immunoglobulins (IgE, G. A. M) by human peripheral blood mononuclear cells (PBMC). It is shown that the enhanced I8 synthesis of GO-stimulated PBMC is dependent on the presence of T cells and monocytes. After stimulation of purified B cells with GC only a slight enhancement of IgM could be detected. Inhibition studies with neutralizing anti-interleukin-4 (IL-4) and anti-IL-6 antibodies revealed that the GC-induced IgE synthesis of PBMC is not dependent on the presence of IL-4 or IL- 6. Stimulation of membrane-separated and co-cultured cell fractions revealed that the GC-induced enhancement of IgA and IgM synthesis is mediated by T-cell derived soluble mediators. The GC- induced IgG and IgE synthesis is dependent upon contact of B cells with monocytes. Antibodies against LFA-1 and ICAM-1 are capable to suppress the GC-induced IgE and IgG synthesis of PBMC. Furthermore, the monocyte expression of lymphocyte function antigen-I (LFA-1), intercellular adhesion molecule-I (ICAM-I) and HLA-DR is modulated by GC stimulation. [ABSTRACT FROM AUTHOR]

We studied the influence of human recombinant soluble interleukin-4 receptors (sIL-4R) and a partial antagonistic mutant IL-4 protein, IL-4(Y124D), on the in vitro CD23 expression, soluble (s)CD23 release and IgE synthesis of human peripheral blood mononuclear cells (PBMC). The data show that sIL-4R suppressed the IL-4-induced IgE synthesis of PBMC. sIL-4R fusion protein stabilized with human Fcγ fragments showed a more pronounced effect than unconjugated sIL-4R. IL-4(Y124D) also suppressed the IL-4-induced IgE synthesis. The IL-4-induced antigen CD23 and its soluble fragments were suppressed by sIL-4R and IL-4(Y124D). PBMC of atopic donors with a spontaneous in vitro IgE synthesis showed a partial suppression of the IgE production after sIL-4R or IL-4(Y124D) application. The IgE synthesis and sCD23 release of normal donor PBMC were suppressed when the substances were applied 0-4 days after IL-4 treatment. After 4 days of IL-4 stimulation, sIL-4R and IL-4(Y124D) enhanced the IgE synthesis. These data demonstrate that sIL-4R and IL-4(Y124D) are suppressive for the primary IgE synthesis induced by IL-4. In contrast, the ongoing IgE synthesis was only partially modulated by sIL-4R and IL-4(Y124D), and in some conditions even an enhancement of the IgE production was observed. These data suggest a differential function for IL-4 in the early and late phase of PBMC IgE production. [ABSTRACT FROM AUTHOR]

Incubation of neutrophils with interferon-alpha (IFN-α) for 5 min and subsequent stimulation with the calcium ionophore A23187 enhanced the production of oxygen radicals, while a suppression was obtained with FMLP-stimulated cells. Similar data were observed for the direct G-protein activator sodium fluoride (NaF). Incubation of the cells with IFN-α and subsequent stimulation with FMLP (in the presence of cytochalasin b) reduced the generation of the chemotactic active leukotriene B4 (LTB4). The metabolism of LTB4 was significantly inhibited. IFN-α decreased the specific binding sites for LTB4 and increased the number of binding sites for FMLP. The GTPase activity as a parameter for the activation of G-proteins was enhanced by IFN-α. Preincubation of the cells with IFN-α and subsequent stimulation with NaF increased the GTPase activity synergistically, whereas co-incubation of IFN-α with FMLP showed additive effects. Our results clearly demonstrate the modulatory effects of IFN-α on granulocyte functions with regard to the receptor-mediated signal transduction. [ABSTRACT FROM AUTHOR]

The penetration depths of bulk Tl2Ba2Ca2Cu3Oy and Tl0:58Pb0:4Sr1:6Ba0:4Ca2Cu3Oy superconductors with the critical temperatures 112 K and 114 K, respectively, were determined from the AC susceptibility measurements. When the samples are in the Meissner state, the dispersive components of AC susceptibility as well as their temperature dependences reflect the changes of the penetration depths at various temperatures. In these bulk ceramic superconductors the penetration depths are of the order of few μm and they are comparable to the grains sizes in the ceramics. [ABSTRACT FROM AUTHOR]

Analyzes the relationship between homocysteine and diabetic neuropathy in patients with Type II diabetes mellitus in Germany. Diagnosis of neuropathy from clinical symptoms; Test by electrophysiological sensory testing and autonomic functions; Role of homocysteine in pathogenesis of diabetic neuropathy.

During the initial phase of respiratory syncytial virus (RSV) infection, when a low virus-cell ratio is most probable, signs of inflammation are detectable in the infected respiratory tissue. Therefore we analysed the release of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, tumour necrosis factor-α (TNF-α), and the soluble form of the TNF receptor-1 (sTNFR-1), from peripheral blood mono nuclear cells (PBMC) after exposure to low infectious RSV doses (multiplicity of infection, MOI, 0.001-1) and incubation times of up to 24 hr. The PBMC secreted IL-8 in a time and virus dose-dependent fashion. As was verified by Northern blot analysis, the increased IL-8 secretion rate was accompanied by an enhanced IL-8 mRNA steady-state level. The infection of the PBMC after 4 hr post-RSV exposure was verified by detection of RSVSH genomic RNA and mRNA after reverse transcription and polymerase chain reaction (PCR) amplification. In addition, after 24 hr post-infection we determined the percentage of infected cells by specific immunofluorescence using monoclonal antibodies directed against the F- and G-proteins. After exposure of PBMC to inactivated RSV, we observed only. RSVSH genomic RNA and a reduced IL-8 release. Thus, even the binding and/or phagocytosis of RSV by PBMC induced an IL-8 synthesis to some extent. Following an incubation time of 24 hr, PBMC exposed to small RSV doses synthesized and released high amounts of IL-6 into the cell supernatant. In contrast, only Iow amounts of TNF-α were released from PBMC. in addition to the release of the proinflammatory cytokines, an enhanced level of the sTNFR-I was measured in the cell supernatants at a MOl of 0.1. However, there was no correlation between TNFR-I membrane expression and cell supernatant concentration. Co-culture experiments performed with PBMC and human epithelial cells (A549) revealed that the enhanced IL-8 secretion profile observed in the coculture was partially dependent on the cytokines TNF-α, IL-1β and TNF-β/lymphotoxin released by the cells themselves. [ABSTRACT FROM AUTHOR]

Incubation of human polymorphonuclear granulocytes, monocytes and platelets with sodium fluoride (NaF) results in a time- and dose-dependent generation of leukotrienes and 12-HETE, respectively. This release was not influenced by pretreatment with pertussis toxin or cholera toxin. The mediators are detectable after a lag phase of about 5–10 min. Inactivation of LTB4 by the neutrophils via omega-oxidation into 20-hydroxy-LTB4 and 20-carboxy-LTB4 is inhibited by NaF. In combination with other cell stimuli, NaF showed modulatory effects, such as an enhanced formation of the lenkotrienes when FMLP, opsonized zymosan, PMA, and arachidonic acid were applied as stimuli. Prestimulation of cells with NaF causes an increased [3H]guanylylimidodiphosphate binding to isolated membrane preparations, indicating an enhanced exchange rate for GDP to GTP. Our data demonstrate that a direct activation of GTP-binding proteins results in the generation of the inflammatory mediators and provides evidence for the involvement of the signal-transduction pathway. [ABSTRACT FROM AUTHOR]