Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate the effect of a continuous calcium infusion on the plasma levels of aldosterone, renin activity, and cortisol in six anephric and four nonnephrectomized patients on regular hemodialysis. In both groups, a significant increase in whole blood ionized calcium (b-Ca2+) was demonstrated. A significant increase in plasma aldosterone (PAC) was noted in the nonnephrectomized patients, in whom the rise in PAC correlated with the increase in b-Ca2+. However, in the anephric patients only a smaller and insignificant increase in PAC was found. No significant changes were demonstrated in plasma cortisol or renin activity, nor in potassium or sodium concentrations in either group. It is concluded that ionized calcium influences the plasma levels of aldosterone in uremic patients on regular hemodialysis.
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PMID:Calcium-dependent aldosterone secretion in anephric and nonnephrectomized patients on regular hemodialysis. 23 32

In this work the Ca2+ response and the morphological changes elicited by Ag in human CD4+ T cells are described at the single cell level. The APC used to present the diphtheria toxoid Ag to a human diphtheria toxoid-specific T cell clone were murine L cell fibroblast transfectants expressing MHC class II molecules. The increase of the intracellular Ca2+ concentration, [Ca2+]i, which is one of the earliest steps of the response to TCR stimulation, was followed by fluorimetry with fura-2 on an imaging system. This response was a specific consequence of successful Ag presentation, because it only took place when fibroblasts expressed both class II MHC molecules and Ag. CD4 molecules were also involved in this intercellular interaction, because the Ca2+ response could be inhibited by preincubating the T cells with an anti-CD4 antibody. The response induced by APC started after a delay of at least 6 min, after which large Ca2+ oscillations took place, with a pseudo period of 100 s at 35 degrees C. The frequency of these oscillations decreased with temperature. The oscillations became progressively more damped during the first 30 to 40 min of cell-to-cell interaction, after which they completely stopped; however, [Ca2+]i remained well above its resting level for more than 1 h after the contact. The Ca2+ oscillations were entirely dependent on Ca2+ influx because they immediately disappeared when external calcium was removed. Similar oscillations were observed when the cells were stimulated with an anti-CD3 antibody. After stimulation with APC, many T cells abandoned their spherical shape and tended to flatten and elongate. This aspect of the T cell response was not observed after stimulation with an anti-CD3 antibody. In the presence of cytochalasin B, the morphologic changes elicited by the APC were blocked, whereas the Ca2+ response was slightly enhanced. However, when T cells were loaded with the Ca2+ chelator BAPTA, both Ca2+ and morphologic changes were inhibited, suggesting that the Ca2+ response plays a permissive role for the morphologic changes.
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PMID:Imaging early steps of human T cell activation by antigen-presenting cells. 134 19

The functional relevance of a direct ethanol effect on the membrane structure of T lymphocytes and accessory cells (APC), as well as on signal transduction systems was studied in ten normal subjects. Ethanol incubation (80 mM for 24h) of highly purified T cells increased the number of CD4+/CD45RA+ lymphocytes. In contrast, ethanol exposure induced a drop in CD14+/LFA-3+ APC values. These changes were accompanied by faulty T-cell proliferation in response to anti-CD3 and anti-CD2 mAb and inhibition of CD3- and CD2-mediated rises in intracellular calcium and, to a lesser extent, inositol 1,4,5-triphosphate levels. These data clearly indicate that a membrane-specific ethanol interaction both modifies surface glycoproteic and/or glycolipidic structures and alters transmembrane transduction of the activation signals.
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PMID:Ethanol-induced CD3 and CD2 hyporesponsiveness of peripheral blood T lymphocytes. 136 75

Although ligation of the CD3/TCR complex initiates an activation signal in T cells, additional costimulatory signals generated during cell-to-cell interactions with APC transduced via ligation of CD11a/CD18 and CD28 by their specific counter-receptor intercellular adhesion molecule (ICAM)-1 and B7, respectively, are required for optimal T cell proliferation and cytokine synthesis. Using soluble IgC gamma 1 fusion proteins of these costimulatory counter-receptors, we have recently shown that unactivated resting CD4+ T cells and Ag-primed CD4+ T cells differ in their response to the costimulation by ICAM-1 and B7. Preferential proliferative responses of resting T and Ag-primed T cells to ICAM-1 and B7, respectively, prompted us to speculate that ICAM-1-induced signals may regulate coupling of the CD28 signaling pathway. Furthermore, both B7 and ICAM-1 are co-expressed on APC and thus, may co-regulate activation-driven maturation of T cells. In this study, we have examined regulatory effects of IgC gamma 1 fusion proteins of B7, ICAM-1, and ICAM-2 (a homologue of ICAM-1) on each other's costimulation. We first demonstrate that TCR-directed costimulation of resting CD4+ T cells with ICAM-1 (ICAM-1 priming) but not ICAM-2 induces increased responsiveness to B7. Priming of CD4+ T cells with ICAM-1 induced higher expression of both CD18 and CD28 than that with either B7 or ICAM-2. Cross-linking of CD28 induced faster and significantly higher cytoplasmic free calcium mobilization response in ICAM-1-primed CD4+ T cells than in resting, B7-primed, or ICAM-2-primed CD4+ T cells. B7 synergized with ICAM-1 but not ICAM-2 to augment proliferative responses of not only resting CD4+ T cells but also those that had been primed with either ICAM. Unlike resting or ICAM-2-primed CD4+ T cells, ICAM-1-primed CD4+ T cells efficiently proliferated in response to the synergistic costimulation of B7 and ICAM-2. In contrast, both ICAM-1 and ICAM-2 inhibit B7-driven proliferation of Ag-primed CD4+ T cells. Thus, B7 and ICAM-1 exert contrasting regulatory effects on the proliferation of CD4+ T cells depending on their state of activation-induced maturation.
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PMID:Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the CD28 counter-receptor B7. 138 17

Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA-DR) expressed on both APC and activated human T cells, and simultaneously bind to certain V beta chains of the TCR. In this report, we compared early T cell signaling events in human alloantigen-stimulated T cells when activated by HLA-DR ligation through antibody cross-linking or by direct enterotoxin superantigen binding. Both types of stimuli induced tyrosine phosphorylation of phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an increase in intracellular calcium concentration; however, superantigen-induced signaling was stronger than class II ligation alone. Antibody-mediated ligation of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased calcium mobilization, consistent with a mechanism of superantigen activity through a combination of class II and CD3/Ti signals. In addition, down-modulation of CD3 receptors with antibody demonstrated that superantigen-induced signaling events were CD3-dependent. Superantigen signaling was also class II-dependent, in that resting T cells were not responsive to direct enterotoxin stimulation. To address how early signal transducing activity correlated with T cell responsiveness, alloantigen-primed T cells were activated with immobilized class II-specific mAb or soluble superantigen. Both HLA-DR mAb-stimulated T cells and enterotoxin-treated T cells proliferated strongly in response to co-stimulation by a combination of CD28 receptor engagement and PMA addition. In addition, superantigen-induced growth was induced by CD28 receptor ligation with antibody or the B7 counter-receptor expressed on Chinese hamster ovary cells. Taken together, these results indicate that class II molecules expressed on activated T cells are directly coupled to the PLC gamma 1 signal transduction pathway, and that coligation of HLA-DR with CD3 augments T cell signaling comparable to that induced by enterotoxin superantigen. Thus, we suggest that superantigen-induced early signaling responses in activated T cells may be due in part to class II transmembrane signals induced when HLA-DR and V beta are ligated in cis.
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PMID:Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in class II+ T cells. 138 26

T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.
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PMID:Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids. 169 58

Activated human T cells express MHC class II and have been shown to present foreign Ag to autologous T cells. We now demonstrate that MHC class II+ T cell clones can present myelin basic protein (MBP) peptide autoantigen in the absence of traditional APC to autologous MBP reactive T cell clones. MBP peptide-pulsed T cell clones specifically stimulated autologous MBP-reactive T cell clones to flux calcium and proliferate. Activation responses were peptide epitope specific and blocked by mAb to MHC class II, indicating a TCR-mediated response. In addition, mAb to the adhesion molecules LFA-3, CD2, LFA-1, CD29, and to the tyrosine phosphatase CD45 also inhibited proliferation, indicating the involvement of T to T cell interactions. In contrast to peptide Ag, T cell clones did not respond to autologous T cells pulsed with HPLC-purified MBP, suggesting that T cells are unable to process whole MBP. However, batch-purified MBP Ag preparations containing lower m.w. breakdown products were presented by T cells, indicating that naturally occurring breakdown products of autoantigens could be presented by activated T cells in vivo. These results raise the possibility that T cell presentation of autoantigen at inflammatory sites may be important in regulation of immune responses to self Ag.
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PMID:Presentation of autoantigen by human T cells. 171 5

Atrial premature beats seldom require an antiarrhythmic treatment; reassurance and suppression of coffee, alcohol, and tobacco generally suffice. Acute atrial fibrillation is best treated by electrical cardioversion if it induces acute cardiovascular decompensation. If it is not poorly tolerated, the arrhythmia may be treated with digitalis at doses sufficient to keep the ventricular response rate at 70-90/min. This therapy may restore sinus rhythm, but conversion to sinus rhythm often requires the combined use of digitalis with a beta-blocker or class I antiarrhythmic drug (quinidine, disopyramide, procainamide, propafenone, or flecainide). Digitalis must be avoided in the presence of a preexcitation, and class IA agents, which facilitate atrioventricular (AV) nodal transport, must never be used without digitalis. Chemical cardioversion may also be achieved by i.v. amiodarone. Long-term prevention of recurrences after cardioversion or in the presence of recurrent paroxysmal atrial fibrillation requires digitalis combined with a class I agent, or a beta-blocker, preferably sotalol. Amiodarone is also very efficacious. Special mention should be made of atrial fibrillations of vagal or sympathetic origin, which are best treated by amiodarone, or beta-blockade (nadolol), respectively. In the presence of chronic established atrial fibrillation, digitalis in combination with a beta-blocking agent or a calcium antagonist, such as verapamil or diltiazem, may be useful to slow the ventricular response rate. If successful control cannot be obtained, catheter ablation of the AV node with implantation of a rate-responsive pacemaker must be contemplated. The therapeutic approach in patients with chronic atrial fibrillation, whether or not associated, is similar to atrial flutter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiarrhythmic treatment of atrial arrhythmias. 172 15

In nonobese diabetic (NOD) mice, T cells play a major role in mediating autoimmunity against pancreatic islet beta-cells. We and others previously reported that age-related alterations in the thymic and peripheral T cell repertoire and function occur in prediabetic NOD mice. To study the mechanism responsible for these T cell alterations, we examined whether a defect exists in the thymus of NOD mice at the level of TCR-mediated signaling after activation by Con A and anti-CD3. We found that thymocytes from NOD mice respond weakly to Con A- and anti-CD3-induced proliferation, compared with thymocytes from control BALB/c, BALB.B, (BALB.B x BALB.K)F1, C57BL/6, and nonobese non-diabetic mice. This defect correlates with the onset of insulitis, because it can be detected at 7 to 8 weeks of age, whereas younger mice displayed a normal T cell responsiveness. Thymic T cells from (NOD x BALB/c)F1 mice, which are insulitis- and diabetes-free, exhibit an intermediate stage of unresponsiveness. This T cell defect is not due to a difference in the level of CD3 and IL-2R expression by NOD and BALB/c thymocytes, and both NOD CD4+ CD8- and CD4- CD8+ mature thymic T cells respond poorly to Con A. BALB/c but not NOD thymic T cells respond to Con A in the presence of either BALB/c or NOD thymic APC, suggesting that the thymic T cell defect in NOD mice is intrinsic to NOD thymic T cells and is not due to an inability of NOD APC to provide a costimulatory signal. The defect can be partially reversed by the addition of rIL-2 to NOD thymocytes. To determine whether a defect in signal transduction mediates this NOD thymic T cell unresponsiveness, we tested whether these cells elevate their intracellular free Ca2+ ion concentration in response to Con A. An equivalent Con A-induced increase in Ca2+ ion concentration in both NOD and BALB/c thymocytes was observed, suggesting a normal coupling between the CD3 complex and phospholipase C in NOD thymocytes. In contrast to their low proliferative response to Con A or anti-CD3, NOD thymocytes respond normally (i.e., as do BALB/c thymocytes) to the combinations of PMA plus the Ca2+ ionophore ionomycin and PMA plus Con A but weakly to Con A plus ionomycin. Our data suggest that the age-related NOD thymocyte unresponsiveness to Con A and anti-CD3 results from a defect in the signaling pathway of T cell activation that occurs upstream of protein kinase C activation.
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PMID:Defective thymic T cell activation by concanavalin A and anti-CD3 in autoimmune nonobese diabetic mice. Evidence for thymic T cell anergy that correlates with the onset of insulitis. 182 15

The protein C anticoagulant system provides important control of the blood coagulation cascade. The key protein is protein C, a vitamin K-dependent zymogen which is activated to a serine protease by the thrombin-thrombomodulin complex on endothelial cells. Activated protein C functions by degrading the phospholipid-bound coagulation factors Va and VIIIa. Protein S is a cofactor in these reactions. It is a vitamin K-dependent protein with multiple domains. From the N-terminal it contains a vitamin K-dependent domain, a thrombin-sensitive region, four EGF) epidermal growth factor (EGF)-like domains and a C-terminal region homologous to the androgen binding proteins. Three different types of post-translationally modified amino acid residues are found in protein S, 11 gamma-carboxy glutamic acid residues in the vitamin K-dependent domain, a beta-hydroxylated aspartic acid in the first EGF-like domain and a beta-hydroxylated asparagine in each of the other three EGF-like domains. The EGF-like domains contain very high affinity calcium binding sites, and calcium plays a structural and stabilising role. The importance of the anticoagulant properties of protein S is illustrated by the high incidence of thrombo-embolic events in individuals with heterozygous deficiency. Anticoagulation may not be the sole function of protein S, since both in vivo and in vitro, it forms a high affinity non-covalent complex with one of the regulatory proteins in the complement system, the C4b-binding protein (C4BP). The complexed form of protein S has no APC cofactor function. C4BP is a high molecular weight multimeric protein with a unique octopus-like structure. It is composed of seven identical alpha-chains and one beta-chain. The alpha- and beta-chains are linked by disulphide bridges. The cDNA cloning of the beta-chain showed the alpha- and beta-chains to be homologous and of common evolutionary origin. Both subunits are composed of multiple 60 amino acid long repeats (short complement or consensus repeats, SCR) and their genes are located in close proximity on chromosome 1, band 1q32. Available experimental data suggest the beta-chain to contain the single protein S binding site on C4BP, whereas each of the alpha-chains contains a binding site for the complement protein, C4b. As C4BP lacking the beta-chain is unable to bind protein S, the beta-chain is required for protein S binding, but not for the assembly of the alpha-chains during biosynthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. 183 51


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