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)

Male and female guinea pigs underwent immunisation with heterologous heart protein (rat heart), complete Freund's adjuvant and pertussis vaccine (immunised) or normal saline (control) at weekly intervals for 6 weeks, and were subsequently studied. In vivo intracardiac pressures, cardiac outputs, blood volumes, in vitro pressure-volume relations, left ventricular collagen contents, light microscopy, direct immunofluorescence, lymphocyte stimulation studies, and serology for circulating anti heart antibody (haemagglutination and radioimmunoassay) were performed. Immunised guinea pigs studied between 5 and 8 weeks following the immunisation protocol demonstrated a 44% increase in LVEDP (p less than 0.005), an increase in right atrial pressure (p less than 0.001), although no change in aortic pressure or cardiac output when compared with controls. Left ventricular weight was increased 20% (p less than 0.001), and in vitro left ventricular volume by 34% (at 8 mmHg distending pressure, p less than 0.001). Lung wet weight was increased 44% (p less than 0.005), and left ventricular collagen content increased 60% (p less than 0.001). Cultured lymphocytes from treated guinea pigs demonstrated a 1.5- to 4.5-fold (dependent upon proximity to last immunisation) increase in radiolabelled thymidine uptake when incubated with guinea pig heart protein compared to controls (p less than 0.001), and circulating anti guinea pig heart antibodies were detected by haemagglutination and radioimmunoassay. Histological examination of the left ventricles revealed inflammatory cell infiltration and myocyte increase to varying degrees in 15 of the 18 treated animals. We conclude that inflammatory, probably immune-mediated, chronic myocarditis can be produced in the guinea pig.
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PMID:Experimental autoimmune myocarditis in the guinea pig. 405 37

Monoclonal antibodies to the alpha L beta 2 integrin inhibit the binding of type I collagen to PMN (polymorphonuclear neutrophil leukocytes) as well as the subsequent stimulation of superoxide production and enzyme secretion-elicited by this collagen. Pepsinized collagen still binds PMN but no longer stimulates them. The I domain of the alpha chain of the integrin is involved in the binding. Two sequences of the alpha 1(I) polypeptide chain of collagen participate in the process. Experiments of competitive inhibition by synthetic peptides showed that the sequence RGD (915-917) is used for binding to the cells and DGGRYY (1034-1039) serves to stimulate PMN. Experiments of radioactive labeling of the cells and affinity chromatography on Sepharose-collagen confirmed the presence in PMN extracts of two proteins, 95 and 185 kDa, respectively, corresponding to the molecular weights of the beta 2 and alpha L chains of the integrin and recognized by their specific monoclonal antibodies. The transduction pathways depending on the alpha L beta 2 integrin do not involve a G protein (ruled out by the use of cholera and pertussis toxins), whereas the cytoskeleton was found to participate in the process, as evidenced by inhibition by cytochalasin B. After collagen stimulation, cytoplasmic inositol trisphosphate and calcium ion increased sharply for less than 2 min. The use of the inhibitors staurosporine and calphostin C demonstrated that protein kinase C was involved. Evaluation of the activity of this enzyme showed that, upon stimulation of PMN with collagen I, it was translocated to plasma membrane. Acrylamide gel electrophoresis of the protein bands corresponding to the integrin alpha L beta 2, followed by immunoblotting using monoclonal antibodies to phosphotyrosine, permitted us to demonstrate that, prior to stimulation by type I collagen, there was no phosphorylation, whereas after stimulation, both alpha L and beta 2 chains were stained by anti-phosphotyrosine antibodies. The adhesion of PMN to pepsinized type I collagen triggered tyrosine phosphorylation of the beta 2 chain of the integrin, without stimulating O2-. production by these cells, whereas their stimulation by complete type I collagen induced the tyrosine phosphorylation of both alpha L and beta 2 subunits. The tyrosine phosphorylation of both integrin subunits during transduction of stimuli is a heretofore undescribed phenomenon that may correspond to a new system of transmembrane communication.
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PMID:The binding of type I collagen to lymphocyte function-associated antigen (LFA) 1 integrin triggers the respiratory burst of human polymorphonuclear neutrophils. Role of calcium signaling and tyrosine phosphorylation of LFA 1. 749 7

Nonopsonized Bordetella pertussis bind to human monocytes by means of the virulence factors filamentous hemagglutinin (FHA), pertactin, and the minor fimbrial subunit FimD. Receptors on monocytes that mediate binding of B. pertussis to these cells include complement receptor type 3 (CR3), which binds to FHA of B. pertussis, and very late antigen-5 (VLA-5), which binds to an, as yet, unknown ligand on these bacteria. In the present study, the possibility that FimD acts as a ligand for VLA-5 was investigated. Soluble fibronectin, which is the natural ligand for VLA-5, or mAbs against VLA-5 inhibited binding to monocytes of B. pertussis strains that express FimD but not of mutant strains that lack FimD. Beads that were coated with the fusion protein maltose-binding protein-FimD bound to adherent monocytes, and this binding was inhibited by soluble fibronectin or mAb against the alpha- or beta-chain of VLA-5, while soluble collagen or mAb against VLA-4, VLA-6, CR3, or HLA class II had no effect. Down-modulation of VLA-5 on the apical surface of monocytes by plating the cells onto surfaces precoated with anti-VLA-5 mAb also inhibited binding of beads coated with maltose-binding protein-FimD to monocytes, while precoating of the surfaces with mAb against VLA-6 or CR3 had no effect. These results indicate that VLA-5 on monocytes serves as a receptor for FimD on B. pertussis. Binding of C3bi-coated erythrocytes to monocytes, which is a measure of the binding activity of CR3, was enhanced when monocytes were adhered onto plates precoated with purified fimbriae of B. pertussis, while precoating with fimbriae lacking FimD had no effect. Precoating of the plates with FimD-containing fimbriae also enhanced binding of B. pertussis, which express FHA, but not of strains that lack FHA, to monocytes. The enhanced binding of C3bi-coated erythrocytes and B. pertussis to monocytes could be markedly inhibited by tyrphostin-47, a protein tyrosine kinase inhibitor. These results demonstrate that interaction of FimD of B. pertussis with VLA-5 on monocytes activates CR3, which requires protein tyrosine kinases and results in enhanced binding of B. pertussis to the latter receptor via FHA.
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PMID:Binding of FimD on Bordetella pertussis to very late antigen-5 on monocytes activates complement receptor type 3 via protein tyrosine kinases. 756 Nov 5

Expression of the OmpU outer membrane protein of Vibrio cholerae is positively regulated by toxR, which also regulates critical virulence factors such as cholera toxin and the toxin-coregulated pilus colonization factor. In this study, we have characterized the 38-kDa OmpU protein and investigated its role in the adhesion of V. cholerae to mammalian cells. The amino-terminal sequence of OmpU has similarity with the sequences of Haemophilus influenzae HMW1 and HMW2 adhesins, which, in turn, also have similarity with the sequence of Bordetella pertussis filamentous hemagglutinin. A monoclonal antibody directed against FHA recognized both V. cholerae OmpU and Escherichia coli OmpA, and polyclonal anti-OmpU antibodies recognized FHA and E. coli OmpA, suggesting the existence of common epitopes among these proteins. OmpU was strongly recognized by convalescent-phase serum from volunteers experimentally infected with virulent V. cholerae strains, indicating that OmpU is immunogenic and produced in vivo. OmpU selectively bound to fibronectin and to an arginine-glycine-asparagine (RGD) tripeptide but not to other matrix glycoproteins tested such as collagen or laminin. Antibodies directed against OmpU or their F(ab)2 fragments completely inhibited adhesion of several V. cholerae strains to HeLa, HEp-2, Caco-2, and Henle 407 epithelial cells and also inhibited intestinal colonization and conferred protection in newborn mice against both biotypes (El Tor and classical) of V. cholerae O1. Collectively, these data indicate that OmpU has adhesive properties which may play a role in the pathogenesis of cholera.
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PMID:The OmpU outer membrane protein, a potential adherence factor of Vibrio cholerae. 759 Oct 82

Angiopeptin (AP: BIM23014C), a cyclic analogue of the peptide hormone somatostatin, inhibits intimal hyperplasia after balloon angioplasty. This inhibition has been attributed to a direct inhibitory effect on smooth muscle cell (SMC) proliferation. However, the SMC that proliferate in the intima and contribute to intimal hyperplasia arrive there by migrating from the injured media, suggesting that SMC migration may also play an important role in this process. Indeed, in the experiments we describe, AP inhibited the migration of rat aortic SMC cells (RA-SMC) in response to type I collagen, the predominant form of collagen in the vessel media, and did so dose dependently. RA-SMC migration was inhibited 70% in the presence of AP 100 nM. RA-SMC adhesion to type I collagen in these conditions was not inhibited, suggesting that AP does not interfere with RA-SMC recognition of type I collagen; instead, it blocks subsequent signaling events that are necessary for RA-SMC migration in response to type I collagen. AP inhibited the forskolin-stimulated accumulation of cyclic AMP by RA-SMC (35% at 30 nM). In addition, pertussis toxin (PT), which blocks Gi-mediated inhibition of adenylyl cyclase, blocked the inhibitory effect of AP on cyclic AMP (cAMP) accumulation and also blocked the inhibitory effect of AP on RA-SMC migration. These findings suggest that the inhibitory effect of AP on intimal hyperplasia is due at least in part to its effects on SMC migration and that these effects are mediated by a Gi-dependent pathway and may involve inhibition of adenylyl cyclase and cAMP accumulation.
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PMID:Angiopeptin (BIM23014C) inhibits vascular smooth muscle cell migration in vitro through a G-protein-mediated pathway and is associated with inhibition of adenylyl cyclase and cyclic AMP accumulation. 759 30

Thrombin binds at least to two sites of the platelet surface; to the recently cloned thrombin receptor [Vu, T. K., Hung, D. T., Wheaton, V. I. & Coughlin, S. R. (1991) Cell 64, 1057-1068] and to glycoprotein Ib. In the present study, the decrease of pertussis-toxin-dependent ADP-ribosylation of membrane and soluble inhibitory guanine-nucleotide-binding alpha (Gi alpha) proteins was measured after platelet stimulation with a thrombin-receptor-activating peptide (TRAP), and compared to stimulation with thrombin. Stimulation of intact platelets with TRAP decreased the pertussis-toxin-dependent ADP-ribosylation of the major membrane 41-kDa Gi alpha protein and the minor soluble 40 kDa Gi alpha protein recently described in platelets [Gennity, J. M. & Siess, W. (1991) Biochem. J. 279, 643-650]. The kinetics and extent of the decrease of pertussis-toxin-dependent ADP-ribosylation after stimulation of TRAP were similar to the effect of thrombin. The decrease of pertussis-toxin-dependent ADP-ribosylation of the soluble Gi alpha protein was more pronounced and observed at lower agonist concentrations than the decrease of the membrane Gi alpha protein. Desensitization of the thrombin receptor by incubating platelets with a low concentration of TRAP reduced the subsequent decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins, evoked by TRAP or thrombin. Platelet stimulation with gamma-thrombin that does not bind to glycoprotein Ib also showed a decrease in the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins. Treatment of platelets with the stable prostacyclin analog, iloprost, reduced the decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins induced by TRAP or thrombin. Among other platelet stimuli tested (endoperoxide/thromboxane analog U44619, collagen, ADP, vasopressin), only U44619 decreased the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins to a degree comparable to TRAP. It is concluded that the thrombin-induced activation of both the membrane and soluble Gi alpha proteins in platelets occurs via stimulation of the recently cloned thrombin receptor and is independent of the binding of thrombin to glycoprotein Ib. Furthermore, the coupling thrombin receptor/Gi protein is reduced by intracellular cAMP.
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PMID:Activation of the cloned platelet thrombin receptor decreases the pertussis-toxin-dependent ADP-ribosylation of the membrane and soluble inhibitory guanine-nucleotide-binding-alpha proteins. Inhibition by the prostacyclin analog, iloprost. 768 67

We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms.
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PMID:Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells. 778 47

The effect of lysophosphatidic acid (LPA) on the proliferation of normal and tumor mouse mammary epithelial cells in primary, serum-free, collagen gel cell culture was evaluated. LPA stimulated the growth of normal mammary epithelial cells from mature virgin mice. The growth of pregnancy-dependent tumors (PDT) was generally stimulated, although the response was attenuated in some of these tumors compared to normal cells. In contrast, the growth of 70% of ovarian-independent tumors (OIT) was inhibited by LPA; the remainder were unaffected. LPA stimulated cAMP accumulation and phosphoinositide (PI) hydrolysis in normal, PDT, and OIT. Thus, the regulation of adenylyl cyclase and PI-specific phospholipase C by LPA is similar in normal and tumor cells. Pertussis toxin (PT) partially inhibited LPA-stimulated growth in normal cells but did not affect LPA-stimulated PI hydrolysis or cAMP accumulation. Thus, PT-sensitive and -insensitive proliferative pathways are activated. PT also inhibited LPA-stimulated growth of PDT but generally had no effect on the growth of OIT. These results show that the mitogenic response to LPA is attenuated in the hormone-dependent phenotype and switches to growth inhibition in hormone-independent tumors. Furthermore, LPA stimulates multiple signal transduction pathways mediated by PT-sensitive and -insensitive G proteins. The PT-sensitive pathways are not tightly coupled to the proliferative response to LPA in tumor cells. These data suggest that alterations in G protein function may occur during tumor progression.
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PMID:Analysis of the proliferative response to lysophosphatidic acid in primary cultures of mammary epithelium: differences between normal and tumor cells. 781 18

Ca(2+)-activated K+ channels play an important role in Ca2+ signal transduction and may be regulated by mechanisms other than a direct effect of Ca2+. Inside-out patches of the apical membrane of confluent transformed rabbit cortical collecting duct cells cultured on collagen were subjected to patch clamp analysis. Two types of K+ channel, of medium and high conductance, were observed. The latter channel was characterized by a K+/Na+ permeability ratio of 10, an inwardly rectified current, a conductance of 80 pS at 0 mV, and an open probability dependent on both voltage and Ca2+. Guanosine 5'-triphosphate (GTP) but not a guanosine 5'-diphosphate (GDP) analogue, adenosine 5'-triphosphate (ATP), cytidine 5'-triphosphate (CTP), or inosine 5'-triphosphate (ITP), inhibited the activity of this Ca(2+)-activated K+ channel. The inhibitory effect of GTP was dose dependent, with a 50% inhibitory concentration of 10(-5) M in the absence of Mg2+. In the presence of Mg2+ (1 mM), which is required for the binding of GTP to G proteins, the 50% inhibitory concentration decreased to 3 x 10(-12) M. Pertussis toxin or cholera toxin (each at 10 ng/ml) did not prevent the inhibitory effect of GTP. After removal of GTP from the medium bathing an inhibited channel, subsequent application of Ca2+ failed to activate the channel. Ca(2+)-activated K+ channels of smooth muscle cells and proximal tubule cells did not respond to GTP. Thus, the Ca(2+)-activated K+ channel in the apical membrane of collecting duct cells is inhibited by GTP, which appears to exert its effect via a G protein that is insensitive to both cholera and pertussis toxins.
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PMID:Regulation by GTP of a Ca(2+)-activated K+ channel in the apical membrane of rabbit cortical collecting duct cells. 796 44

Pseudopod protrusion at the leading edge is a characteristic of migrating tumor cells as they traverse vascular subendothelial basement membranes to establish metastases. A micropipette system has been developed to study the dynamics of pseudopod protrusion in individual human melanoma cells in response to type IV collagen, a component of basement membranes. Soluble type IV collagen stimulates chemotaxis of A2058 melanoma cells through a G protein-coupled receptor, and induces an early burst of intracellular calcium (Savarese et al., 1992, J. Biol. Chem. 267, 21928-21935). A micropipette filled with type IV collagen solution (100 micrograms/ml) was positioned so that the tip was adjacent to a cell suspended in Dulbeceo's modified Eagle's medium. Within 10 min, tumor cells generated a pseudopod which entered the micropipette with an average velocity of 0.24 micron/min and proceeded to lengthen for 40 min. Pseudopods from individual cells ranged from 7.5-10 microns at this time and were characterized by an irregular shape which did not fill the lumen of the micropipette. Pretreatment of cells with pertussis toxin (0.5 microgram/ml), which inhibits cell migration by approximately 90% (but not the calcium burst), blocked formation of the irregular, extended pseudopod, while allowing a much smaller outpouching, or bleb, to form. Lengths of such blebs from individual PT-treated cells reached a plateau at approximately 20 min and ranged from 2.2-4.0 microns at the end point. Treatment of cells with bis-(amino-phenoxy)ethane tetraacetic acid (75 microM), an intracellular Ca2+ chelator, blocked initial bleb formation and prevented extension. From these observations we hypothesize that tumor cell pseudopod protrusion induced by soluble type IV collagen takes place in distinct, separable phases: an initial convex, symmetrical outpouching, caused by localized Ca(2+)-activated actin depolymerization and osmotic flux, followed by an extension with an irregular shape, which requires G protein-mediated actin polymerization.
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PMID:Two phases of pseudopod protrusion in tumor cells revealed by a micropipette. 802 14


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