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

Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration-dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh-Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino-6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys-Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25-dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells.
 ...
PMID:Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells. 131 32

Acellular vaccines against whooping cough are in the final stage of clinical testing and are likely to become available for mass immunization in the near future. Over a dozen vaccines of similar composition have been developed by vaccine companies and research laboratories; all of them contain a detoxified form of pertussis toxin (PT) that may be present alone or combined with one or more other non-toxic proteins, such as filamentous haemagglutinin (FHA), pertactin (69 kDa), and the agglutinogens (AGG). Most of the vaccines contain a PT that has been inactivated by chemical treatment, a process that reduces the immunogenicity of the molecule and may not completely eliminate the risk of reversion to toxicity. To avoid these problems, we have constructed by genetic manipulation a mutant of Bordetella pertussis that produces a non-toxic form of PT. This molecule (PT-9K/129G) contains two amino acid substitutions in the S1 subunit (Arg9-->Lys and Glu129-->Gly) which abolish the enzymatic activity of the S1 subunit and all the toxic properties of PT, without changing the immunological properties of the wild-type toxin. Following extensive preclinical studies, which have shown that PT-9K/129G is safe and more antigenic than the toxin treated with chemical agents, this molecule was tested for safety and immunogenicity in adult volunteers, 18-month-old children and 2-month-old infants. The molecule has been tested alone, combined with FHA and pertactin and also combined with diphtheria and tetanus toxoids.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Progress towards the development of new vaccines against whooping cough. 147 24

The prn gene encoding the 68 kDa protective outer-membrane protein of Bordetella bronchiseptica (P.68 pertactin) was cloned, sequenced and expressed in Escherichia coli. The gene was isolated by DNA:DNA hybridization experiments using a radioactively-labelled fragment of the homologous prn gene from Bordetella parapertussis. DNA sequence analysis reveals that the gene is capable of encoding a protein with a molecular mass of 93996 Da (P.94); this precursor molecule is processed to form the P.68 antigen on the surface of B. bronchiseptica. Heterologous expression of the full-length gene encoding P.94 in Escherichia coli results in similar processing, with the P.68 antigen targeted to the bacterial outer membrane. Comparison of P.94 with the P.93 and P.95 precursors, encoding homologous proteins from Bordetella pertussis and B. parapertussis, shows a high degree (greater than 90%) of homology. The major differences between all three proteins occur in the number of repeats of the two families (Gly-Gly-Xaa-Xaa-Pro)n and (Pro-Gln-Pro)n of reiterated sequence motifs.
 ...
PMID:Cloning, nucleotide sequence and heterologous expression of the protective outer-membrane protein P.68 pertactin from Bordetella bronchiseptica. 152 10

Parameters of ligand binding, stimulation of low-Km GTPase, and inhibition of adenylate cyclase were determined in intact human neuroblastoma SH-SY5Y cells and in their isolated membranes, both suspended in identical physiological buffer medium. In cells, the mu-selective opioid agonist [3H]Tyr-D-Ala-Gly(Me)Phe-Gly-ol ([3H]DAMGO) bound to two populations of sites with KD values of 3.9 and 160 nM, with less than 10% of the sites in the high-affinity state. Both sites were also detected at 4 degrees C and were displaced by various opioids, including quaternary naltrexone. The opioid antagonist [3H]naltrexone bound to a single population of sites, and in cells treated with pertussis toxin the biphasic displacement of [3H]naltrexone by DAMGO became monophasic with only low-affinity binding present. The toxin specifically reduced high-affinity agonist binding but had no effect on the binding of [3H]naltrexone. In isolated membranes, both agonist and antagonist bound to a single population of receptor sites with affinities similar to that of the high-affinity binding component in cells. Addition of GTP to membranes reduced the Bmax for [3H]DAMGO by 87% and induced a linear ligand binding component; a low-affinity binding site, however, could not be saturated. Compared with results obtained with membranes suspended in Tris buffer, agonist binding, including both receptor density and affinity, in the physiological medium was attenuated. The results suggest that high-affinity opioid agonist binding represents the ligand-receptor-guanine nucleotide binding protein (G protein) complex present in cells at low density due to modulation by endogenous GTP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Opioid signal transduction in intact and fragmented SH-SY5Y neural cells. 156 Feb 22

Alterations in brain opioid binding and opioid pharmacodynamics following chronic (8-day) naltrexone (NTX) treatment were determined in pertussis toxin (PTX)-treated mice. Intrathecal (IT) and intracerebroventricular (ICV) PTX produced a time-dependent, long-lasting inhibition of morphine (SC) analgesia without modifying basal nociception. Inhibition was maximal 16 days following PTX treatment, and was still observed at 40 days. Relative to placebo controls, NTX treatment produced supersensitivity to morphine analgesia in all control mice and in mice pretreated with PTX 1 day before NTX. Supersensitivity was not observed in 7-day PTX-pretreated mice. [3H][D-Ala2-D-Leu5]enkephalin ([3H]DADLE) and [3H][D-Ala2-MePhe4-Gly(ol)5]enkephalin ([3H]DAMGO) binding sites were increased by NTX treatment in saline- and PTX-pretreated groups. KDs were unchanged. These results indicate that PTX does not alter opioid antagonist-induced receptor upregulation. However, PTX treatment can diminish morphine potency in upregulated and control mice. Therefore, opioid analgesia in control and upregulated mice appears to be mediated by receptors linked to a common PTX-sensitive G-protein. Furthermore, in 7-day PTX-pretreated mice, NTX increased binding sites without altering morphine potency, which suggests that new binding sites can appear without being functionally coupled.
 ...
PMID:Dissociation of opioid receptor upregulation and functional supersensitivity. 165 19

The effects of i.c.v. treatment with pertussis toxin (PTX) on the motivational effect of opioid agonists were examined in mice. Morphine (0.1-10 nmol, i.c.v.), [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAGO, 0.001-0.1 nmol, i.c.v.), a selective mu-opioid receptor agonist, and [D-Pen2, D-Pen5]enkephalin (DPDPE, 1-15 nmol, i.c.v.), a selective delta-opioid receptor agonist, produced a dose-related place preference in mice. Administration of PTX (0.5 micrograms, i.c.v.) to mice resulted in no preference for either the drug- or vehicle-associated place. Pretreatment with PTX abolished the place preferences induced by DAGO (0.1 nmol), morphine (10 nmol) and DPDPE (15 nmol). These findings demonstrate that the appetitive effects of opioids result from the activation of central mu- and delta-receptors, and suggest that PTX-sensitive GTP-binding proteins in the central nervous system may be involved in the motivational effects of mu- and delta-opioid agonists.
 ...
PMID:Pertussis toxin abolishes mu- and delta-opioid agonist-induced place preference. 166 84

Epitopes defined by monoclonal antibodies (mAb) specific for the Bordetella pertussis outer membrane protein P.69 (pertactin) were mapped using a series of amino- and carboxy-terminal deletion mutants expressed in Escherichia coli. mAb were found to bind predominantly to a region of pertactin spanning a (Pro-Gln-Pro)5 repeat motif and one mAb was found to bind to another region spanning a (Gly-Gly-Xaa-Xaa-Pro)5 repeat motif. To localize further the mAb-binding sites, a panel of synthetic peptides, a series of 94 overlapping hexameric peptides, and a P.69 30-amino acid fusion to a hepatitis B core protein (HBcAg-69), were synthesized. This combined approach has identified the binding site for the mAb BBO5: Pro-Gly-Pro-Gln-Pro-Pro; mAb BBO7, E4A8 and E4D7: Ala-Pro-Gln-Pro-Pro-Ala-Gly-Arg; and mAb BPE3: Thr-Leu-Trp-Tyr-Ala-Glu-Ser-Asn-Ala-Leu-Ser-Lys-Arg. We have used a non-lethal murine respiratory model of B. pertussis infection to investigate the ability of a peptide containing the epitope of the mAb BBO5 to elicit protective immunity. Immunization of mice with the HBcAg-69 protein prevented growth of B. pertussis in the lungs compared to mice receiving HBcAg alone, and protection correlated with high titers of anti-P.69 antibodies.
 ...
PMID:Identification and characterization of a protective immunodominant B cell epitope of pertactin (P.69) from Bordetella pertussis. 170 65

3H-Labelled kappa-elastin peptides (kE:75 kDa molecular weight) were shown to bind to confluent human skin fibroblast (HSF) cultures in a time-dependent and saturable manner. Scatchard analysis indicated the presence of high affinity binding sites with kD = 2.7 x 10(-10) M and 19,000 sites per cell. Binding of kE to its receptor on HSF accelerates and intensifies the adhesion of insoluble elastin fibres (iE) to confluent HSF. Optimal effect was attained for a kE concentration of 0.3 x 10(-9) M close to kD. This stimulatory effect of kE on the binding of iE to HSF could be inhibited by neomycin, retinal and pertussis toxin, substances which act at different levels of the transduction mechanism following the activation of the receptor and the subsequent triggering of cell biological events (chemotaxis, modification of calcium fluxes). The stimulation of iE adhesion to HSF induced by kE as well as kE binding to the cells could be inhibited by lactose and laminin but not by Arg-Gly-Asp-Ser(RGDS) peptides. This indicates that the elastin peptide receptor on HSF possesses lectin-like properties and shares homology with the laminin receptor as also shown for other cell types. None of the substances tested, that is inhibitors of the transduction mechanism, lactose, laminin and Arg-Gly-Asp-Ser(RGDS) peptides were shown to interfere significantly with the binding of iE (in the absence of added kE) to confluent HSF. The proteins adhering strongly to elastin fibres were isolated by a sequential extraction procedure and the final hydrochloride guanidinium-DTT extract was analysed by SDS-PAGE under reducing conditions, Western blots using specific antibodies against several connective tissue proteins and affinity for [3H]-kE following nitrocellulose electro-transfer of proteins. Fibronectin, vitronectin, tropoelastin(s), and a 120 kDa cysteine rich glycoprotein previously designated as elastonectin were identified. Among these proteins, [3H]-kE was found to bind exclusively to a 65 kDa protein that could be eluted selectively from elastin fibres with a neutral buffer containing 100 mM lactose. Therefore the elastin peptide receptor on human skin fibroblasts shares properties with the elastin receptor characterized from other cell types. Conformational differences between elastin peptides and elastin fibres could explain the differences in the mechanisms of interactions between elastin fibres and elastin peptides with HSF in culture. The stimulatory effect of elastin-derived peptides on the adhesion of elastin fibres to HSF could have implications in the oriented biosynthesis of elastin fibres.
 ...
PMID:Mechanisms of interaction between human skin fibroblasts and elastin: differences between elastin fibres and derived peptides. 172 59

The plasmid pBRD026, which directs expression of the B subunit of the Escherichia coli heat-labile toxin (LTB), was modified so that DNA encoding epitopes could be inserted at the 3' end of the gene. An oligonucleotide linker containing restriction sites for BglII and SpeI was inserted at the SpeI site at the 3' end of the LTB gene to form plasmid pFV1. This linker also encodes the amino acid sequence Gly-Pro-Gly-Pro which we propose acts as a 'hinge' between the LTB and the foreign epitope. Oligonucleotides specifying an epitope from the Bordetella pertussis P.69 outer membrane protein were cloned into pFV1 to form pFV169. The resultant fusion protein (LTB69) was partially purified from the periplasm of E. coli strains in a soluble pentameric form which could bind GM1 gangliosides. Mice immunized intranasally with purified LTB69 produced antibodies against both LTB and the P.69 protein. In addition, ELISPOT assays demonstrated the presence of LTB-specific and P.69-specific antibody-secreting cells in the lungs of immunized mice.
 ...
PMID:Intranasal immunization using the B subunit of the Escherichia coli heat-labile toxin fused to an epitope of the Bordetella pertussis P.69 antigen. 172 57

A 69-kDa protein has been identified on the surface of the Gram-negative pathogen Bordetella pertussis that can elicit a protective immune response in animal models. This protein is associated with virulent strains of B. pertussis but its function has remained unclear. In this report we demonstrate that purified preparations of the 69-kDa outer membrane protein can promote the attachment of Chinese hamster ovary (CHO) cells. The interaction between the mammalian cells and this protein can be specifically inhibited by an Arg-Gly-Asp (RGD)-containing synthetic peptide that is homologous with a region found in the 69-kDa protein sequence. These studies indicate that a specific cell binding site containing an Arg-Gly-Asp sequence may be involved in the interaction of this bacterial protein with mammalian cell surfaces. To further investigate the role of this protein as a bacterial adhesin, a mutant of B. pertussis W28 that does not express the 69-kDa protein was constructed using the plasmid vector pRTP1. This mutant was 30-40% less efficient at adhering to CHO cells and to human HeLa cells than was the parent strain. These data support a role for this 69-kDa outer membrane protein in the attachment of B. pertussis to mammalian cells. We propose the name "pertactin" for this protein.
 ...
PMID:Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells. 198 35


1 2 3 4 5 6 7 8 9 10 Next >>