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Biomedical subjects

A Falus

Publications and source records attributed to A Falus.

At least 127 records · Page 7Linked to original sources

Inhibition of IgE production by epsilon (epsilon) chain-specific antisense oligonucleotides (AOs) studied on human myeloma cell line U266 and peripheral blood mononuclear cells of a patient with hypereosinophilia.

Based on cDNA sequence data epsilon chain-specific antisense oligonucleotides were synthesized and checked on in vitro IgE production. Using peripheral blood cells from a hypereosinophilic patient and a human IgE myeloma cell line, U266, marked reduction of in vitro IgE production measured by PRIST was observed. The effect of epsilon antisenses proved to be isotype specific since IgG production by both peripheral blood cells and a lymphoma cell line, CESS, was not affected. Moreover, the expression of other markers on U266 (interleukin-6 receptor and gp130) were not influenced by epsilon-specific antisense oligonucleotides.

Humans↗

Molecular biology and role of histamine in physiological and pathological reactions. A review.

Histamine is known to exhibit a wide variety of both physiological and pathologic functions in different tissues and cells, this amine is one of the most general mediators of the mammalian organism. Extracellular histamine action is believed to be mediated by binding to its specific cell-surface receptor(s) resulting in the converting the extracellular signal to intracellular events. Moreover, numerous studies suggest basic role for intracellular histamine as one of the intracellular messenger moieties. The functional consequences of the action of histamine involve many physiological and pathophysiological events, including allergy, neurotransmission and cell growth.

Histamine↗

A trace element preparation containing zinc increases the production of interleukin-6 in human monocytes and glial cells.

The in vitro effects of a trace element preparation (béres Drops Plus, BDP) on the biosynthesis of inflammatory cytokines interleukin (IL-6, IL-1, and tumor necrosis factor-alpha (TNF-alpha) were studied in human peripheral monocytes. The production of IL-6 was studied in a glioblastoma cell line, SKMG-4, as well. The trace element preparation BDP significantly stimulated both the constitutive and the endotoxin or IL-1 induced IL-6 production in monocytes or in glial cells, respectively, but revealed no or only modest effect on IL-1 and TNF-alpha production of monocytes. Moreover, BDP was able to reduce the inhibitory effect of a synthetic corticosteroid, dexamethasone on the biosynthesis of IL-6. The positive effect of the trace element preparation on the IL-6 production of monocytes from rheumatoid arthritis (RA) patients is comparable, to that of on the monocytes from healthy individuals, and similarly to healthy individuals was negligible on the IL-1 and TNF-alpha production. The detailed analysis of the composition of the preparation suggested, that the major active component in the stimulation of IL-6 production is Zn, but for the complete effect other trace elements are also required.

Adjuvants, Immunologic↗

The role of T-lymphocytes and cytokines in rheumatoid arthritis.

In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.

Animals↗

Endotoxin and fibrinogen degradation product-D have different actions on carbohydrate metabolism: role of Kupffer cells.

The effect of endotoxin-derived lipopolysaccharide (LPS) and fibrinogen degradation product D (FDPD) on oxygen consumption and glycogenolysis in the perfused rat liver was investigated. 1. Infusion of LPS (100 micrograms/ml) or FDPD (7 micrograms/ml) caused a rapid stimulation of oxygen uptake by the perfused liver of 10-12 mumol/g/h. 2. LPS also caused a transient increase in glucose and lactate release into the perfusion medium from endogenous glycogen; however, FDPD was without effect. 3. Destruction of Kupffer cells by GdCl3 pretreatment blocked the effects of LPS and FDPD on oxygen uptake and glycogenolysis. Further, LPS and FDPD had no effect on oxygen consumption by isolated hepatocytes. Therefore, it is concluded that Kupffer cells are involved in the increase of hepatic oxygen consumption and carbohydrate release caused by LPS, most likely via release of PGE2 and PGD2. Since FDPD increased oxygen but not carbohydrate release, it is concluded that it acts via stimulating the release of mediators distinct from those released following LPS infusion.

Animals↗

Cytokine networks and corticosteroid receptors.

The role of the inflammatory cytokines on glucocorticosteroid binding (GCSB) and glucocorticosteroid receptor (GR) level was studied. We incubated a B cell line--CESS--, a promonocytic cell line--U937--and a hepatoma cell line--HepG2--in the presence of varying concentrations of IL-1 beta, IL-6 and TNF-alpha for 24 hours. Glucocorticosteroid binding was determined by the method of "whole cell uptake," and characterized by Scatchard analysis. A considerable increase in the glucocorticosteroid binding was induced by all the three cytokines. Northern analysis of the glucocorticoid receptor expression demonstrates that the action of the cytokines is likely not pretranslational. Present data suggest that local imbalance in the ratio of these three cytokines in different pathological cases might influence the glucocorticosteroid sensitivity of the lymphocytes, monocytes and hepatocytes as target cells.

Cells, Cultured↗

[Detection of hepatitis C viral RNA by polymerase chain reaction].

The authors describe the development and the application of polymerase chain reaction (PCR) in the detection of hepatitis C virus. Based on the sequence data available in the literature, a conservative motif at the 5' end of the virus genome has been selected for amplification. Using the flanking synthetic oligonucleotides the specificity of the highly sensitive RNA-PCR assay was proved by serologically positive and negative serum samples. HCV-RNA-PCR studies were applied to start interferon treatment in patients from National Institute of Rheumatology and Physiotherapy (Budapest) with anti-HCV positive serum samples and this method was used to evaluate the efficacy of interferon therapy, as well.

Genome, Viral↗

Human cytokines interleukin (IL)-3 and IL-6 affect the growth and insulin binding of the unicellular organism Tetrahymena.

Interleukin (IL)-3 and IL-6 significantly increase the growth rate of the unicellular organism, Tetrahymena. The effect elicited by IL-3 is long lasting as it was also detectable after 20 generations. Effect of IL-6 was detectable as long as the substance was present in the cell culture. Pretreatment with IL-3 did not enhance the proliferative response to subsequent IL-3 treatment, but the second exposure to IL-3 considerably depressed the active proliferation of Tetrahymena cells. However, a positive 'priming effect' elicited by IL-6 resulted in an increased growth rate following repeated IL-6 stimulation. Insulin binding to the plasma membrane of Tetrahymena was increased by IL-6 but not by IL-3 after 24 hours, and this enhancement appeared even after one hour incubation. If the cells were pretreated with insulin, IL-6 did not influence insulin binding, while an inhibition by IL-3 was observed. These results direct attention to the similarities of actions induced by IL-3 and IL-6 at different levels of phylogeny probably due to the presence of cytokine receptor-like structures on this unicellular organism.

Animals↗

Cholinergic signals to and from the immune system.

This article reviews recent data from our laboratory towards the impact of the autonomous nervous system on mutual interactions between the immune system and the central nervous system. Using a pharmacological approach in rats it is shown that shifts in the adrenergic/cholinergic balance in vivo affect in vitro functions of the non-specific and specific immune system, whereby adrenergic and cholinergic stimulation in general have opposite effects. A high degree of integration appears to exist between cells of the immune system with the cholinergic system. Lymphocytes were found to react to acetylcholine, but are also able to produce and to degradate this neurotransmitter. In addition, changes in the cholinergic tonus were found to affect immune signaling to the brain and to protect thymocytes from apoptosis, possibly via a direct effect on thymic epithelial cells.

Adrenergic Agents↗

The effect of WSEWS pentapeptide and WSEWS-specific monoclonal antibodies on constitutive and IL-6 induced acute-phase protein production by a human hepatoma cell line, HEPG-2.

Interleukin-6 receptor (IL-6R) is a member of the cytokine receptor superfamily characterised by the obligatory presence of WSXWS (Trp-Ser-X-Trp-Ser) sequence motif near the transmembrane domain. To more clearly understand the role of this motif, we treated the HepG2 hepatoma cell line with synthetic WSEWS peptide (E is glutamic acid) and checked the spontaneous and IL-6-induced production of acute-phase protein fibrinogen and C1-inhibitor (C1-INH). The peptide revealed a definitely stimulatory effect both on the constitutive synthesis of C1-INH and on the IL-6-induced fibrinogen synthesis of HepG2 cells. Monoclonal antibody specific for WSEWS pentapeptide was stimulatory for the spontaneous secretion of both fibrinogen and C1-INH. However, the IL-6-induced elevations of these acute-phase proteins were oppositely regulated, since the anti-WSEWS monoclonal antibody was inhibitory on the production of fibrinogen induced by IL-6 but strongly augmented the IL-6 induced production of C1-INH. Our study indicates that the WSEWS motif is critical in the effect of IL-6 on the acute-phase protein production influencing either the ligand binding by the WSEWS-containing receptor molecule or the signal transduction.

Acute-Phase Proteins↗

Cytokine receptor architecture, structure and genetic assembly.

In this review major structural and molecular characteristics of interleukin-6-type cytokine receptors consisting of ligand-specific (e.g., IL-6 receptor) and public (gp130) elements are outlined. The peculiar shedding feature of the ligand-binding receptor subunit provides a possibility to form a receptor-ligand complex in the soluble phase, followed by an autocrine or paracrine re-attaching to the membrane bound gp130. This situation provides a dynamic 4-chain model for IL-6-type receptors, depending on a critical balance between membrane bound and soluble cytokine receptors. The generation and transduction of intracellular signal for IL-6-type cytokine receptors based primarily on generation of phospho-tyrosine proteins. In this set of events kinases of the JAK family are basically involved. Although not all primary substrates are uncovered, gp130 and stat proteins are phosphorylated. The variability of the JAK/Stat system and its still not clear relation to the specificity of cytokine actions are discussed.

Antigens, CD↗

Enhancement of interleukin-6 production by fibrinogen degradation product D in human peripheral monocytes and perfused murine liver.

The effect of fibrinogen degradation products D and E (FDP-D, FDP-E) on IL-6 production in perfused mouse livers and peripheral monocytes is studied. Similarly to bacterial endotoxin FDP-D is highly potent to augment the IL-6 production measured in perfused mouse livers, while FDP-E is not stimulatory. FDP-D but not FDP-E is able to stimulate the in vitro IL-6 production of human peripheral monocytes, as well. Plasmin alone is almost ineffective on IL-6 production both in perfused livers and monocytes. Our findings suggest a direct positive feedback circuit, among fibrinogen, FDP and IL-6.

Adult↗

Dehydroepiandrosterone modulates the spontaneous and IL-6 stimulated fibrinogen production of human hepatoma cells.

The role of an androgen, dehydroepiandrosterone (DHEA) has been studied on the constitutive and IL-6 induced fibrinogen production of HepG-2 cells. DHEA markedly augments the constitutive fibrinogen production of the hepatoma cells in a dose dependent fashion. Oppositely, for IL-6 induced fibrinogen production, DHEA is strongly inhibitory. The effectiveness of DHEA on the constitutive fibrinogen production is further potentiated if the hepatoma cells are preincubated with a glucocorticosteroid, dexamethasone. These findings demonstrate that the complex interaction between the steroid- and cytokine-directed regulation of the production of acute phase proteins is further coloured by the action of androgens on immune and hormonal systems.

Carcinoma, Hepatocellular↗

The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zinc containing trace element preparation.

A trace element preparation (Béres Drops Plus, BDP) elevates the number of glucocorticoid receptors (gcR) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients. This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin (IL)-6. There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha (TNF alpha)-induced changes of gcRs. The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation, since the augmenting effect was abolished if BDP did not contain zinc.

Arthritis, Rheumatoid↗

[Interleukin-6: friend or enemy? Latest findings on the clinical aspects of IL-6].

The authors summarize the recent findings obtained in the field of inflammatory cytokines with particular attention on interleukin-6 (IL-6). After a short review of the molecular biology and of the cellular effects of IL-6, the most important clinical relations of IL-6 in hepatic diseases, in non-specific inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and in certain autoimmune diseases are provided. The simultaneous discussion of molecular and clinical data contribute to the understanding of pathomechanisms.

Autoimmune Diseases↗

Separate regulation of a membrane protein, gp130, present in receptor complex specific for interleukin-6 and other functionally related cytokines.

In addition to specific ligand binding elements, receptor assembly for interleukin(IL)-6, oncostatin-M, leukaemia inhibitory factor, ciliary neurotrophic factor and IL-11 includes an additional unit, gp130. This molecule is a transmembrane glycoprotein of 130 kDa. In this paper, reviewing molecular, biochemical and functional data on gp130, we describe the dissimilar action of IL-3 on the expression of the binding unit of the IL-6 receptor and that of gp130. According to FACS studies, resting basophils express only IL-6 receptors and no gp130 molecules on the plasma membranes. After incubation with IL-3, the surface appearance and de novo transcription of gp130 was shown by FACS and mRNA polymerase chain reaction analysis.

Antigens, CD↗