Multiple G-protein-coupling specificity of beta-adrenoceptor in macrophages.

Adrenergic signalling of the immune system is one of the important modulator pathways of the inflammatory immune response realized via G protein-mediated pathways. The resulted signal depends on the type of the receptor-coupled G-protein (GPCR) that, according to the classical paradigm in the case of beta-adrenergic receptor (beta-AR), is Gs-type. Recently, alternate and/or multiple G protein coupling specificity of GPCRs have been demonstrated including a switch from Gs to Gi binding.

The catecholamine cytokine balance: interaction between the brain and the immune system.

Cytokines are involved both in various immune reactions and in controlling certain events in the central nervous system (CNS). In our earlier studies, it was shown that monoamine neurotransmitters, released in stress situations, represent a tonic sympathetic control on cytokine production and on the balance of proinflammatory/anti-inflammatory cytokines. Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, while inflammatory mediators might also have a role in its etiology.

Dual beta-adrenergic modulation in the immune system: stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages.

This is the first study to demonstrate that the interaction between beta-adrenoceptor activation, and the production of inflammatory mediators can be modulated in opposite ways by two inflammatory stimuli, namely, protein kinase C (PKC)-activating phorbol myristyl acetate (PMA) and lipopolysaccharide (LPS). We provided evidence that isoproterenol treatment, when combined with phorbol ester increased the production of tumor necrosis factor-alpha, interleukin-12, and nitric oxide in murine macrophages, as well as in human monocytes and differentiated PLB-985 cells, while in agreement with earlier findings, it decreased inflammatory mediator production in combination with LPS stimulation. The contrasting effect on inflammatory mediator production, shown for the PMA and LPS activated cells was accompanied by parallel changes in activation of ERK1/2 and p38 MAPKs.

Endotoxin-induced TNF-alpha production changes inversely to its plasma level during pregnancy.

Objective: To study plasma TNF-alpha levels during normal pregnancy and the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells.

Study Design: In a longitudinal prospective study the ex vivo endotoxin-induced TNF-alpha production of peripheral blood cells and the plasma level of TNF-alpha in 18 women with uncomplicated pregnancies were determined at the 8th, 17th, 27th and 36th weeks of their pregnancy and 48 h and 6 weeks post-delivery. TNF-alpha levels were determined by ELISA technique.

The inducibility of TNF-alpha production is different in the granulocytic and monocytic differentiated forms of wild type and CGD-mutant PLB-985 cells.

Chronic granulomatous disease is an inherited disorder associated with a defect in phagocytic cell oxidative metabolism resulting in ineffective microbicidal activity. Consequently, patients with chronic granulomatous disease suffer from recurrent infections. Published data show that besides the failure to produce superoxide and its derivatives, other functional problems can also be found in chronic granulomatous disease-mutant cells.

Intact noradrenaline transporter is needed for the sympathetic fine-tuning of cytokine balance.

Earlier studies demonstrated that cytokine production is under the tonic control of noradrenaline. As the level and/or the duration of noradrenaline action is regulated by the noradrenaline transporter (NET), which is also a target of antidepressant treatment, we studied its role in the regulation of the cytokine response during inflammation. The endotoxin-evoked tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 response was studied in genetically produced noradrenaline transporter-deficient (NET-KO) mice and by treatment with desipramine, a monoamine uptake-blocker antidepressant.

Immunomodulatory effect of antidepressants.

Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, whereas other arguments cite the role of inflammatory mediators in the etiology of psychiatric disorders. A bidirectional interaction between the monoamine system and the inflammatory system might explain the concurrent therapeutical efficacy and immunomodulatory features of antidepressants.

Platelet-activating factor evokes Ca2+ transients after the blockade of ryanodine receptor by dantrolene in RAW 264.7 macrophages.

In the present study we studied platelet-activating factor (PAF)-, and ATP-induced increases in intracellular Ca2+ concentration ([Ca2+]i) using RAW 264.7 macrophages filled with fura-2/AM and imaged with fluorescence video microscopy. We found that the prevalence of detectable [Ca2+]i responses to PAF application was significantly higher in the presence of dantrolene.

Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice.

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response.

Cytokines and the central nervous system.

Cytokines are involved both in the immune response and in controlling various events in the central nervous system, that is, they are equally immunoregulators and modulators of neural functions and neuronal survival. On the other hand, cytokine production is under the tonic control of the peripheral and the central nervous system and the cytokine balance can be modulated by the action of neurotransmitters released from nonsynaptic varicosities [131]. The neuroimmune interactions are therefore bidirectional-cytokines and other products of the immune cells can modulate the action, differentiation, and survival of neuronal cells, while the neurotransmitter and neuropeptide release play a pivotal role in influencing the immune response.

Streptozotocin-induced diabetes alters the oligomerization pattern of acetylcholinesterase in rat skeletal muscle.

Aims/hypothesis: Diabetes mellitus has a serious effect on most of the properties of skeletal muscles. Changes in neuromuscular transmission are also involved in propagating the disease.

Methods: In our experiments, acetylcholinesterase was extracted from the fast extensor digitorum longus and slow soleus muscles of control, non-treated 6-week-diabetic and insulin-treated diabetic rats.

Synthesis and biological activity of the structural analogues of (-)-cabenegrin A-I.

A series of phenylbutene and butanol derivatives (6a-j, 12, 13, 15, 17, 24b,c, 26, 27a,b) were prepared from the readily available resorcinol derivatives 2a-f and 7-hydroxy-chroman (18). The products were tested for inhibitory activity on the LPS-induced TNF-alpha production in the plasma in comparison with that of cabenegrin A-I (1a).

Contribution of differently localized alpha 2- and beta-adrenoceptors in the modulation of TNF-alpha and IL-10 production in endotoxemic mice.

Evidence is presented that the immune response to endotoxemia is under tonic control of the sympathetic nervous system. Adrenergic agents may influence the immune response both directly through alpha- and beta-adrenergic receptors expressed by immunologically competent cells and indirectly via alteration of the endogenous NA level by influencing the activity of release-regulating presynaptic alpha 2-adrenoceptors located on the sympathetic nerve terminals. In the immunomodulatory effect of NA/adrenergic drugs, their action on beta-adrenoceptors was dominant, but the considerable role of alpha-adrenoceptors on macrophages was also demonstrated.

Opposite role of alpha2- and beta-adrenoceptors in the modulation of interleukin-10 production in endotoxaemic mice.

Our aim was to investigate the role of adrenoceptors in the modulation of in vivo interleukin-10 (IL-10) production in lipopolysaccharide (LPS)-treated mice. The effect of different adrenergic drugs on plasma concentration of IL-10 was measured by ELISA 90 min after LPS injection. Our results confirmed the involvement of beta-adrenoceptors since the beta-agonist isoproterenol significantly increased the IL-10 production in response to LPS stimulation, whereas the beta-antagonists propranolol decreased it.

Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-alpha production by alpha2- and beta-adrenoceptors in mice.

In the present study, the regulation of tumor necrosis factor-alpha (TNF-alpha) production by alpha2- and beta-adrenoceptors located on noradrenergic nerve terminals and on macrophages was studied in endotoxaemic mice. We found that reduction of the sympathetic outflow by reserpine dramatically increased the lipopolysaccharide (LPS)-induced TNF-alpha production, demonstrating that the release of endogenous noradrenaline (NA), controlled by presynaptic alpha2-adrenoceptors, was a determinant factor in this model. By using alpha2- and beta-adrenergic drugs (clonidine, CH-38083, isoproterenol, propranolol) we provided the first in vivo evidence that, beside the dominance of neuronal alpha2- and macrophage beta-adrenoceptors, the alpha2-adrenoceptors on macrophages were also involved in the modulation of LPS-induced TNF-alpha production.

The polymorphic human TLX-B/CD46/MCP system and its implications in transplantation and reproduction.

TLX antigens have been found on most peripheral blood cells, trophoblasts, seminal vesicle cells and sperms. These antigens seem to be associated with the membrane cofactor protein (MCP) and the CD46 antigen. Alloantibodies to TLX antigens with Fc tau RII-blocking features were obtained by transfusion of leucocytes or platelets.

Molecular characterization of beta-thalassemia in Hungary.

We have identified seven different beta-thalassemia mutations and one delta beta-thalassemia determinant (the Sicilian type) in 32 members of 17 Hungarian families. The most common mutation is the IVS-I-1 (G-->A) change; its high frequency is comparable to that observed in neighboring Czechoslovakia. Additional mutations are of Mediterranean origin.

Differences in the isoelectric focusing patterns of serum and cerebrospinal fluid transthyretin.

Transthyretin isolated by polyacrylamide gel electrophoresis from human serum and cerebrospinal fluid, dissociated into its subunits, was subjected to isoelectric focusing in polyacrylamide gels containing 8 mole/L urea. The isoelectric focusing multi-component patterns of serum and cerebrospinal fluid transthyretin differ in a characteristic way, having only one main protein zone in common. Double diffusion immunotest and immunoblotting revealed the immunological identity of serum and cerebrospinal fluid transthyretin and of the main components separated by isoelectric focusing.

[Study of the origin of hyperglycemia in acute myocardial infarct].

In order to clarify the origin of hyperglycaemia, blood glucose, glycated haemoglobin (GHb) and protein-corrected serum fructosamine (SFA) values were simultaneously determined at admission of 65 patients with acute myocardial infarction while oral glucose tolerance test was performed later at discharge. In 29 patients no alterations in carbohydrate metabolism were found (blood glucose: 5.2 +/- 0.

[Genetic traits in the area of Bodrogköz].

In 1984 a late malaria endemic area, called Bodrogköz was studied. This was a reexamination of the population genetic work performed by Walter, Nemeskéri. In six villages of Bodrogköz 328 persons were tested for AB0, Rh blood groups, haptoglobins, haemoglobin concentration, haematocrit, erythrocyte amount, the MCV, the MCH and the G-6-PD were analyzed.

TCR gamma/delta bearing lymphocytes in peripheral blood of allogenic bone marrow transplanted patients.

The presence of two distinct T-cell receptors (TCR) alpha/beta and gamma/delta dimers as well as of the activated T cells was analysed in peripheral blood mononuclear cells from seventeen recipients of allogeneic bone marrow transplants for leukemia and for severe aplastic anemia. Nine of seventeen recipients expressed an elevated percentage of T cells bearing TCR gamma/delta receptors in their peripheral blood. Seven out of nine cases having elevated gamma/delta positive cells showed chronic graft-versus-host (GVH) disease; one patient was treated with Cyclosporin A, and one patient was asymptomatic.

Plasma desorption mass spectrometry of haemoglobin tryptic peptides for the characterization of a Hungarian alpha-chain variant.

S-Aminoethylated-alpha A and -beta A globin tryptic peptides separated by reversed-phase high-performance liquid chromatography have been analysed by plasma desorption mass spectrometry. Almost all the expected alpha A and beta A tryptic fragments were tentatively assigned relative to the known globin chain sequences based on the molecular weight obtained by plasma desorption mass spectrometric analysis of the purified peptides. The application of plasma desorption mass spectrometry for structure elucidation of a haemoglobin alpha-chain variant revealed the first case of Hb Hasharon in Hungary.

Decrease in the carbamylcholine-induced chemotaxis of monocytes in myasthenia gravis.

The carbamylcholine-induced chemotaxis of monocytes was decreased in patients with myasthenia gravis, whereas no change was found in the C5a-induced locomotion of these cells compared with that of the normal controls. The decrease in the chemotaxis induced by carbamylcholine correlated with the severity of clinical symptoms. The beneficial effect of thymectomy was also reflected in the improvement of chemotaxis.

[T gamma-lymphoproliferative disease].

The case of a rare type of T-cell malignant lymphomas, clinically with a relatively favorable course, a T gamma-lymphoproliferative disease (T gamma-cell chronic lymphocytic leukaemia) was presented. The cytomorphological, cytochemical, immuncytochemical and cytogenetical markers and functional tests of the peripheral blood lymphocytes from the patient were tested. The leukaemic cells with light- and electron microscopy showed the so called LGL (large granular lymphocyte) morphology with multifocal reactions of acid hydrolase enzymes.

Locus assignment of human alpha-globin structural mutants by selective enzymatic amplification of alpha 1 and alpha 2-globin cDNAs.

We have used the powerful methodology of DNA enzymatic amplification in order to assign human alpha-globin structural mutants to one of the two highly homologous alpha-globin genes. Selectively amplified alpha 1 and alpha 2-globin cDNAs were dot-blotted and further hybridized to synthetic oligonucleotides encompassing either the normal or the mutated sequences. The generated signals corresponded specifically to one of the two alpha-globin genes.