Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulation of granulocyte macrophage-colony stimulating factor (GM-CSF) by interleukin-1 (IL-1) has been shown to be counteracted in different mesenchymal cell systems by cyclic adenosine monophosphate (cAMP) agonists. The aim of this study was the evaluation of different cAMP agonists on GM-CSF expression in human bone marrow stromal cells. Incubation of secondary haematopoietic progenitor cell deprived human stromal cell cultures with IL-1 or TNF-alpha induced GM-CSF protein expression in culture supernatants and GM-CSF-mRNA in adherent stromal cells. The coincubation with 8-bromo-cAMP (8BrcAMP), a water soluble cAMP analogue, inhibited this GM-CSF stimulation at the protein and the mRNA level. This effect was dose dependent with a maximal inhibition of about 65% occurring at a 8BrcAMP concentration of 0.75 mM. In addition to 8BrcAMP, other cAMP agonists such as dibutyryl-cAMP, forskolin, pertussis toxin, or prostaglandin E2 (PGE2) had the same inhibitory effect on GM-CSF stimulation by IL-1. Coincubation with the cyclooxygenase inhibitor indomethacin had no significant influence on GM-CSF expression in stromal cells. Our results provide evidence that the previously described inhibitory effect of cAMP agonist PGE2 on haematopoietic progenitor cells in vivo is, at least in part, mediated by modulating the expression of GM-CSF in bone marrow stromal cells.
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PMID:cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cells in vitro. 970 7

The lipid antigens used in the Bordet-Wassermann and prepared by Landsteiner and Marie for syphilis tests from 1909 to 1949 were non specific but have certain common features with the spirochete body. For more than forty years the Bordet-Wassermann reaction, associated with flocculation (Kahn) or agglutination (Kline-VDRL) was used to detect cases of tremonematosis despite frequent false positives reactions due to other infections. In 1949, the Nelson and Mayer test was introduced. This test was based on a rigorously specific reaction based on an antigen of live virulent Treponema pallidum. Culture being impossible, the strain had to be, and still is, maintained by weekly passage on rabbit testicles. These manipulations are very dangerous and the technique is difficult, being performed only in specialized laboratories. This test however made it possible to identify the specificity of lipid tests and led to the development of specific immunofluorescent reactions (FTA) in 1959 and of hemagglutination test (TPHA) in 1969. In 1980, we introduced a simple treponemic reaction (FTA or TPHA) associated with a lipid reaction (VDRL) for screening. The specificity of these tests is not however perfect and the Nelson test remains useful as a highly specific reaction. A simple test with comparable specificity was long awaited and is now available with immunoblotting as for HIV, boreliosis and pertussis, etc. We propose this new reaction to replace the Nelson test because it is specific, is sensitive early, distinguishes between IgG and IgM and is not dangerous to manipulate. We have tested it in over one hundred selected sera of CSF from subjects with recent, former or nervous syphilis as well as cases susceptible of producing false positive reactions and have concluded that immunoblotting is highly specific and sensitive. We recommend official approval of this test to replace the Nelson test.
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PMID:[Immunoblotting for the serodiagnosis of syphilis. A candidate to replace the Nelson-Mayer test]. 1007 52

We investigated the physiology and function of P2Y receptors expressed in human dendritic cells (DCs) differentiated in vitro from CD14+ cells (DC-14). These were obtained after a 10 day stimulation period in GM-CSF, IL-4 and monocyte conditioned medium. DC-14 were found to express high amounts of MHC class II, B7, CD40 as well as CD83. The functional analysis, using single cell Ca2+ imaging, demonstrated the expression of at least three subtypes of P2Y receptors. We further found using patch-clamp measurements that ATP evoked a pertussis toxin insensitive non-selective cation current with a peak current amplitude of -276+/-43 pA (holding potential -80 mV, n = 23). This current was not Ca(2+)-activated, since it was still observed under conditions of high intracellular Ca2+ buffering and could be blocked by Gd3+ (0.5 mM). In addition, intracellular application of GTP-gamma-S (0.3 mM) also activated the current. Interestingly, DC-14 redirected the orientation of their dendrites as well as cell shape towards a pipette containing ATP as observed with time lapse microscopy. These data suggest that in human DCs, ATP acts via P2Y receptors and induces chemokine effects.
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PMID:Expression and a role of functionally coupled P2Y receptors in human dendritic cells. 1009 97

We have used the Stamper-Woodruff frozen-section assay (FSA) to characterize the integrin and activation steps involved in adhesion of peripheral blood eosinophils and neutrophils to nasal polyp endothelium (NPE). Eosinophil and neutrophil adhesion was significantly inhibited by monoclonal antibodies (mAbs) against CD18 (beta2) and CD11a-c. Eosinophil adhesion was also inhibited to a lesser extent by mAbs against CD29 (beta1), CD49d (alpha4), and vascular cell adhesion molecule-1. The involvement of integrins raised the possibility of an activation step being involved in the adhesion process. Although stimulation of the cells with granulocyte macrophage colony-stimulating factor (GM-CSF) before the assay failed to modulate adhesion, binding was inhibited by up to 50% by treatment of the leukocytes with azide. In addition, neutrophil adhesion was completely abrogated by pertussis toxin (PT) and inhibited by about 50% by the platelet-activating factor antagonist WEB 2086 and antibodies against interleukin (IL)-8 and the two IL-8 receptors IL8RA and IL8RB (C-X-CR1 and -CR2). In contrast, eosinophil adhesion was unaffected by PT, WEB 2086, or anti-IL8R mAbs. mAbs against CCR-3, IL-3, IL-5, and GM-CSF also had no effect. This study demonstrates that eosinophil and neutrophil adhesion to NPE in the FSA conforms to the multistep paradigm for leukocyte adhesion and can be used to model the molecular basis for adhesion to endothelium in the context of chronic inflammatory disease. Using this assay, we have observed significant differences in integrin usage between eosinophils and neutrophils and a striking difference in the mechanism of integrin activation. These differences could explain, in part, the preferential accumulation of eosinophils in diseases such as asthma.
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PMID:Characterization of the integrin and activation steps mediating human eosinophil and neutrophil adhesion to chronically inflamed airway endothelium. 1034 Sep 44

In mice whose Gi/o-protein function had been impaired by antisense 'knock-down' or pertussis toxin treatment, i.c.v. injection of myr+-Gi/o alpha subunits restored the effectiveness of beta-endorphin, morphine, DPDPE, clonidine and neurotensin to produce antinociception. Myr+-G alpha subunits of the class of G-proteins actually impaired were more effective than unlike but related myr+-G alpha subunits. Selectivity was noted in that only exogenous myr+-G alpha subunits affected (enhanced) the activity of agonists in G alpha-deficient signalling systems. This treatment had little effect on agonist potency when the impairment resided at the receptor level. The potential of the opioids, clonidine and R-PIA to increase G alpha-related in vitro hydrolysis of GTP was also re-established after injecting myr+-Gi2 alpha subunits into Gi2-knocked-down mice. Myr+-Gi2 alpha subunits pre-incubated with GTPgammaS or GDPbetaS before i.c.v. injection did not improve the activity of agonists in vivo (antinociception) or in vitro (regulation of low Km GTPase). After impairing the function of PKCbeta1 by antisense treatment or with the inhibitor H7, the effect of myr+-G alpha subunits on agonist potency was prevented. Electron microscope analysis showed the entry of gold-conjugated myr+-G alpha subunits into neural cells. These particles were found in the cytoplasm, associated with the plasma membranes of different neuronal processes and also in synaptic junctions. In cultured neurons and astrocytes myr+-Gi2 alpha-associated fluorescence was internalised in a dose-dependent manner and distributed in the plasma membrane and cytosol, as well as in nuclei of dividing astrocytes. Thus, G alpha subunits in CSF enter into neurons and functionally couple to the receptor-triggered signalling cascade. As G-proteins have been implicated in the pathophysiology of several neural disorders, this finding may be valuable in the therapy of such dysfunctions.
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PMID:Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice. 1060 81

Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA, induced significant cytolysis of B lymphoma cells compared with Lym-1 and PMA alone. The effect of PMA was independent of the ability of the compound to stimulate neutrophil-respiratory burst. In fact, first, neutrophils from a patient with chronic granulomatous disease were cytolytically effective in spite of their inability to produce oxidants. Second, various kinase inhibitors exerted different effects on the PMA-stimulated cytolytic system and neutrophil-oxidative burst. Previous studies have shown the involvement of the FcgammaRII, CD11b-CD18 integrins, and CD66b glycoproteins in the Lym-1 mAb-dependent cytolysis by GM-CSF-stimulated neutrophils. The present PMA-stimulated system was inhibited by the anti-FcgammaRII mAb IV.3, the anti-CD18 mAb MEM 48, and the anti-CD11b mAb 2LPM19c but not by the anti-CD66b mAb 80H3 and N-acetyl-D-glucosamine. Furthermore, the PMA- and GM-CSF-stimulated cytolysis was insensitive and sensitive to inhibition by pertussis toxin, respectively. Thus, the use of PMA and GMCSF as neutrophil stimulants uncovers the existence of distinct mechanisms of Lym-1 mAb-mediated cytolysis.
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PMID:Monoclonal Lym-1 antibody-targeted lysis of B lymphoma cells by neutrophils. Evidence for two mechanisms of FcgammaRII-dependent cytolysis. 1107 5

The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations (< 100 ng/mL) but acts as an inhibitor at higher concentrations. Using both flow cytometry (FITC-Annexin-V/PI labeling) and cytology (Diff-Quick staining) approaches, we found that VAA-I could not modulate neutrophil apoptosis at low concentrations but could induce it in >98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.
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PMID:Activation of human neutrophils by the plant lectin Viscum album agglutinin-I: modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis. 1112 52

As there is still a high mortality of the large cell anaplastic non Hodgkin lymphoma (ALCL) (between 40-70%, depending on prognostic factors) there is a need for new therapeutic approaches. Therefore, we studied different strategies for cancer immunotherapy in an immunogenic ALCL tumor model system: A murine IL-9 dependent T cell line was transfected with IL-9 cDNA, resulting in an autonomous growing T cell line designated G6BB, which had a high tumor incidence after injecting of as few as 10(4) cells subcutaneously into syngeneic C57Bl/6 mice. Tumor growth, dissemination, histology, and immunohistochemistry were similar to human ALCL. This mouse model provides an immunogenic in vivo system to investigate antitumor immunotherapies. In order to increase antigen recognition by T cells and T cell activation, we administered tumor bearing mice cell-based cancer vaccines with irradiated tumor cells alone or in combination with immunostimulating CpG-Oligonucleotides, a combination of Th1 cytokines and Th2 cytokine antibodies (IL-12, IFN-gamma, GM-CSF, Anti-IL-10) (after detecting a Th2 cytokine profile in G6BB), or the recall antigens diphtheria, pertussis, and tetanus.
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PMID:[New immunotherapeutic approaches for the treatment of anaplastic large cell lymphoma in a mouse model]. 1121 40

The presence of endothelin-1 receptor proteins and the expression of their specific mRNAs were studied using 1st passage confluent monolayers of articular chondrocytes, isolated from 1-month and 18-month-old rats following 24-h incubation with several growth factors and cytokines. The ET-1- binding sites were predominantly of ETA subtype since BQ123, but not IRL1038 (ETB receptor subtype agonist), effectively blocked 125I-ET-1 binding. The 18-month-old rat cell monolayers bear approximately twice as many 125I-ET-1-binding sites as the 1-month-old rat cells. PDGF, EGF, and IGF-1 increased the number of binding sites in a concentration-dependent manner in both old and young rat cells with PDGF being the most active and EGF more active than IGF-1. IL-1beta, more potently than LPS, increased the number of binding sites in young rat cells only, whereas b-FGF, TGF-beta and GM-CSF had no effect or decreased slightly 125I-ET-1 binding in both types of cells. TNF-alpha strongly decreased the number of binding sites on both young and old rat cells, only. RT-PCR showed an increased expression of the specific ETA mRNA with the age of animals and in the presence of 50 ng/ml PDGF BB only. The incubation of the cells with ETs 1-3 for 10 min resulted in a 50% decrease of cellular cAMP but the blocking of the receptors with BQ123 prior to their exposure to ETs had no effect on cAMP production whereas IRL1038 counteracted this effect only marginally. This suggests a receptor-independent mechanism for ETs-induced inhibition of cAMP production. However, a 10-min co-incubation of cells with ET-1 and with one of the following agents: cholera toxin, pertussis toxin, indomethacin, L-NMA, U73122 and calphostin resulted in an almost complete (calphostin) or partial suppression of ET-1-induced inhibition of cAMP production. The significance of these findings is unclear but the increased density of ET-1 binding sites on old rat cells and its regulation by certain growth factors or cytokines suggest the involvement of ET-1 in aging and possibly in age-related diseases.
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PMID:Endothelin-1 receptors on cultured rat articular chondrocytes: regulation by age, growth factors, and cytokines, and effect on cAMP production. 1129 69

Chemokines have been implicated in regulation of various aspects of hematopoiesis, including negative regulation of the proliferation of immature subsets of myeloid progenitor cells (MPCs), chemotaxis of MPCs, and survival enhancement of MPCs after delayed growth factor addition. Since chemokine receptors are seven-transmembrane-spanning G-protein-linked receptors and the chemotactic effect in vitro of the CXC chemokine SDF-1 is pertussis toxin (PT)-sensitive, implying the involvement of G alpha i proteins as mediators of SDF-1-induced chemotaxis, we evaluated the effects of PT on other chemokine actions influencing MPCs. While the in vitro survival-enhancing effects of SDF-1 on GM-CSF and steel factor-dependent mouse bone marrow granulocyte macrophage progenitors (CFU-GM) were pertussis toxin-sensitive, the suppressive effects of the CC chemokine MIP-1 alpha and the CXC chemokine IL-8 on colony formation by GM-CSF and steel factor-sensitive CFU-GM were insensitive to pertussis toxin. These results suggest that not all chemokine-mediated effects on MPCs are necessarily mediated through pertussis toxin-sensitive G alpha i proteins.
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PMID:Chemokine regulation of hematopoiesis and the involvement of pertussis toxin-sensitive G alpha i proteins. 1145 98


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