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)

Experimental autoimmune uveitis (EAU) is an organ-specific autoimmune disease and has served as a model of certain ocular inflammatory conditions in man. The present study was aimed at separating the effects of MHC and non-MHC genes on the development of EAU in the rat. EAU-susceptible LEW (RT1l), EAU-resistant WKAH (RT1k), and WKAH.1L (RT1l) MHC congenic strain of WKAH background rats were immunized with retinal soluble antigen (S-Ag) in Freund's complete adjuvant (FCA). LEW rats showed typical EAU, while neither WKAH nor WKAH.1L congenic rats developed EAU. However, when an additional i.v. injection of Bordetella pertussis was given, all rat strains developed EAU. Furthermore, when immunized with peptide M, an 18-mer synthetic peptide, which corresponds to amino acid positions 303-320 of bovine S-Ag, and given an additional i.v. injection of B. pertussis, LEW and WKAH.1L rats developed EAU, whereas WKAH did not. When ACI (RT1avl), BUF (RT1b), LEJ (RT1j), W (RT1k), F344 (RT1lvl), BN (RT1n), NIG-III (RT1q), TO (RT1t), and SDJ (RT1u) rats were immunized with peptide M or S-Ag and then B. pertussis, all strains developed EAU by immunization with S-Ag plus B. pertussis, but only F344 and NIG-III developed EAU by immunization with peptide M. These findings suggest that susceptibility to EAU in rats is controlled by both MHC and non-MHC genes; and that in the absence of B. pertussis adjuvant, the form of disease induced by native S-Ag in FCA is governed by non-MHC gene(s). However, this effect of non-MHC gene(s) could no longer be observed when the rats were also injected with B. pertussis adjuvant at sensitization.
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PMID:Regulation of experimental autoimmune uveitis in rats--separation of MHC and non-MHC gene effects. 174 50

Mutants of Bordetella pertussis deficient in virulence-associated factors were identified by using the transposon Tn5 lac. Tn5 lac is a derivative of Tn5 which generates promoter fusions for beta-galactosidase. Tn5 lac insertions in the vir-regulated genes of B. pertussis were identified by selecting for kanamycin-resistant mutants that expressed beta-galactosidase when the vir-regulated genes were expressed but not when the vir-regulated genes were turned off. Fourteen different mutations in vir-regulated genes were identified. Two mutants were deficient in the production of the filamentous hemagglutinin, two mutants were deficient in the production of adenylate cyclase toxin and hemolysin, and one mutant was deficient in the production of dermonecrotic toxin. One insertion mapped adjacent to the pertussis toxin gene, but the mutant produced pertussis toxin. The phenotypes of the remaining eight mutants were not determined, but the mutants did not appear to be deficient in the production of the 69,000-dalton outer membrane protein (agglutinogen 3) or the capsule. Screening for mutations in either of the fimbrial genes proved to be problematic since the parental strain was found to switch from a fimbriated to a nonfimbriated state at a high frequency, which was suggestive of the metastable expression of pili in other bacteria. We used Southern blot analysis with a 30-mer specific for the fimbrial sequences. No bands with the predicted increase in size due to the 12 kilobases from Tn5 lac were observed, which suggests that none of these genes were mutated. Southern blot analysis also revealed that seven of the eight unidentified mutations mapped to different restriction fragments, which suggests that they could be deficient in as many as seven different genes.
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PMID:Use of the promoter fusion transposon Tn5 lac to identify mutations in Bordetella pertussis vir-regulated genes. 256 47

The effects of thermocyclers and primers on the reproducibility of banding patterns in randomly amplified polymorphic DNA analysis were tested. Purified Bordetella pertussis DNA was analysed with four primers (12-mer), which did not differ from each other in their GC-content. Three different thermocycler models from two manufacturers were tested. Three of the primers produced consistent banding patterns in separate wells of the reaction plates of individual thermocyclers, and in different thermocycler models. In contrast, the fourth primer showed extensive between-instrument variation, and the within-instrument variation with this primer was acceptable only when the most advanced thermocycler model was used. We conclude that only primers that provide consistent banding patterns in different environments should be chosen for interlaboratory use in randomly amplified polymorphic DNA analysis. The primers showing variability in banding patterns can only be used if they produce consistent results in the thermocycler used.
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PMID:Effects of thermocyclers and primers on the reproducibility of banding patterns in randomly amplified polymorphic DNA analysis. 793 14

Prosaposin, the precursor of sphingolipid activator protein (saposins A-D), has been identified as a neurotrophic factor capable of inducing neural differentiation and preventing cell death. The putative prosaposin receptor was partially purified from baboon brain membranes by affinity chromatography using a saposin C-column. The purified preparation gave a single major protein band with an apparent molecular weight of 54 kDa on SDS-PAGE. Affinity cross-linking of 11 kDa 125I-saposin C demonstrated the presence of a 66 kDa product, indicative of an apparent molecular weight of 55 kDa for the receptor. A GTP gamma S-binding assay using cell membranes from SHSY5Y neural cells demonstrated agonist stimulated binding of [35S]-GTP gamma S upon treatment with prosaptide TX14(A) a peptide from the neurotrophic region; maximal binding was obtained at 2 nM. TX14(A) stimulated binding was abolished by prior treatment of SHSY5Y cells with pertussis toxin and by a scrambled and an all D-amino acid-derivative of the 14-mer. A 14-mer mutant prosaptide (6N-->6D) competed with TX14(A) with a Ki of 0.7 nM. Immunoblot analysis using an antibody against the G0 alpha subunit demonstrated that the purified receptor preparation contained a 40 kDa reactive band consistent with association of G0 alpha and the receptor. These findings indicate that the signaling induced by prosaposin and TX14(A) is generated by binding to a G0-protein associated receptor.
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PMID:Prosaposin receptor: evidence for a G-protein-associated receptor. 938 93

Prosaposin, the precursor of saposins A, B, C, and D, was recently reported to be a neurotrophic factor in vivo and in vitro. The neurotrophic region of prosaposin has been localized to a 12-amino acid sequence within the saposin C domain and has been used to derive biologically active synthetic peptides (14-22 residues), called prosaptides. Treatment of primary Schwann cells and an immortalized Schwann cell line, iSC, with a 14-mer prosaptide, TX14(A) (10 nM), enhanced phosphorylation of mitogen-activated kinases ERK1 (p44 MAPK) and ERK2 (p42 MAPK) within 5 min, which was blocked by 4 h pretreatment with pertussis toxin. Furthermore, incubation of Schwann cells with the nonhydrolyzable GDP analog GDP-betaS inhibited TX14(A)-induced ERK phosphorylation. TX14(A) enhanced the sulfatide content of primary Schwann cells by 2.5-fold, which was inhibited by pretreatment with pertussis toxin or the synthetic MAP kinase kinase inhibitor PD098059. In addition, TX14(A) increased the tyrosine phosphorylation of all three isoforms of the adapter molecule, Shc, which coincided with the association of p60Src and PI(3)K. Inhibition of PI3(K) by wortmannin blocked TX14(A)-induced ERK phosphorylation. These data demonstrate that TX14(A) uses a pertussis toxin-sensitive G-protein pathway to activate ERKs, which is essential for enhanced sulfatide synthesis in Schwann cells.
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PMID:Prosaptide activates the MAPK pathway by a G-protein-dependent mechanism essential for enhanced sulfatide synthesis by Schwann cells. 950 74

Prosaposin, the precursor of saposins A, B, C, and D, was recently identified as a neurotrophic factor in vitro as well as in vivo. Its neurotrophic activity has been localized to a linear 12-amino acid sequence located in the NH2-terminal portion of the saposin C domain. In this study, we show the colocalization of prosaposin and ganglioside GM3 on NS20Y cell plasma membrane by scanning confocal microscopy. Also, TLC and western blot analyses showed that GM3 was specifically associated with prosaposin in immunoprecipitates; this binding was Ca2+-independent and not disassociated during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The association of prosaposin-GM3 complexes on the cell surface appeared to be functionally important, as determined by differentiation assays. Neurite sprouting, induced by GM3, was inhibited by antibodies raised against a 22-mer peptide, prosaptide 769, containing the neurotrophic sequence of prosaposin. In addition, pertussis toxin inhibited prosaptide-induced neurite outgrowth, as well as prosaptide-enhanced ganglioside concentrations in NS20Y cells, suggesting that prosaposin acted via a G protein-mediated pathway, affecting both ganglioside content and neuronal differentiation. Our findings revealed a direct and tight GM3-prosaposin association on NS20Y plasma membranes. We suggest that ganglioside-protein complexes are structural components of the prosaposin receptor involved in cell differentiation.
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PMID:Colocalization and complex formation between prosaposin and monosialoganglioside GM3 in neural cells. 983 29

Analysis of peptide binding to human neutrophils (PMN) using phage display techniques has revealed cell-specific motifs reactive with the PMN surface. Phage libraries displaying either linear 9-mer or cyclic 10-mer and 6-mer peptides were incubated with normal human neutrophils followed by elution of bound phage with low pH (pH 2.2) and non-ionic detergent. Three rounds of selection generated several related peptide sequences that bound with high avidity to PMN. Using the linear 9-mer library, PMN-binding phage expressed peptides with the motif (G/A)PNLTGRW. The binding of phage bearing this motif was highly specific since no binding was observed on lymphocytes, fibroblasts, epithelial, or endothelial cells. Functional assays revealed that phage bearing the sequence FGPNLTGRW induced a pertussis toxin-sensitive increase in PMN cytosolic calcium analogous to that observed with Galphai coupled receptors. Other prominent motifs identified included phage bearing the consensus DLXTSK(M/L)X(V/I/L), where X represents a non-conserved position. Phage with this motif bound exclusively to a sub population of human PMN that comprised approximately 50% of the total and did not elicit a calcium response. The binding of such phage to PMN was prevented by co-incubation with competing peptides displaying identical or similar sequences (IC50 range from 0.6 micromol/L to 50 micromol/L for DLXTSK and GPNLTG, respectively). We speculate that these techniques will be useful in identifying functional cell-specific binding motifs and contribute to the development of new therapeutic and diagnostic strategies in human disease.
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PMID:Cell-specific peptide binding by human neutrophils. 1002 4

A retro-inverso 11-mer peptidomimetic of prosaposin, Prosaptide D5, induced neurite outgrowth in NS20Y neuroblastoma cells and enhanced [35S]GTPgammaS binding to rat synaptosomal membrane at low nanomolar concentrations similar to prosaposin. Intramuscular injection of D5 ameliorated thermal hyperalgesia in the Seltzer rat model of neuropathic pain, returning paw withdrawal latency to control levels within 3 h after treatment. The effect was sustained for at least 48 h after injection. Prosaposin and D5 inhibited K+-stimulated synaptosomal 45Ca2+ uptake similar to omega-conotoxin MVIIC, demonstrating that both effectors modulated voltage-dependent calcium channels (VDCC); inhibition was largely abolished by pretreatment with pertussis toxin before D5 treatment. The results suggest a mechanism whereby VDCC are modulated by a pertussis toxin-sensitive G-protein coupled receptor; D5 binds to this receptor and thereby ameliorates hyperalgesia in the Seltzer model of neuropathic pain.
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PMID:Prosaptide D5 reverses hyperalgesia: inhibition of calcium channels through a pertussis toxin-sensitive G-protein mechanism in the rat. 1064 16

Recently, the design of beta-sheet proteins and concomitant folding studies have attracted increasing attention. A unique natural all-beta domain occurs in a family of cytolytic bacterial toxins, the so-called RTX toxins. This domain consists of a variable number (about 6-45) of tandem repeats of a glycine-rich nine-residue motif with the consensus sequence GGXGXDX(L/I/F)X. The analysis of the three-dimensional structure of alkaline protease from Pseudomonas aeruginosa which possesses six of these repeats revealed that they fold into a novel 'parallel beta-roll' where calcium is bound within the turns connecting the beta-strands. A 75-mer peptide of the sequence NH(2)-WLS-[GGSGNDNLS](8)-COOH was chemically synthesised. Circular dichroism spectroscopy showed that this polypeptide folds in the presence of Ca(2+) and polyethylene glycol into a beta-structure which is presumably identical with the parallel beta-roll. This synthetic beta-roll behaves similarly to the isolated beta-roll domains from Escherichia coli haemolysin or Bordetella pertussis cyclolysin in terms of calcium binding and polymerisation behaviour.
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PMID:Folding of a synthetic parallel beta-roll protein. 1073 29

The sigma(1)-receptor is a one-transmembrane endoplasmic reticulum protein that binds neurosteroids and dextrorotatory benzomorphans. The roles of sigma(1)-receptors in regulating intracellular Ca(2+) in NG108 cells were examined in this study. sigma(1)-Ligands pregnenolone sulfate, (+)-pentazocine, and 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate hydrochloride modulate Ca(2+) signaling in NG108 cells via two modes of action. First, nanomolar concentrations of the ligands, without effect by themselves, potentiated the bradykinin-induced increase of the cytosolic free Ca(2+) concentration in a bell-shaped manner. This effect of sigma(1)-ligands was unaffected by depletion of Ca(2+) from perfusion buffer and was blocked by a 21-mer antisense oligodeoxynucleotide against the cloned sigma(1)-receptors. Second, after the cells were depleted of the endoplasmic reticulum Ca(2+) stores, the depolarization (75 mM KCl)-induced increase in cytosolic free Ca(2+) was potentiated by 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate hydrochloride, whereas it was inhibited by pregnenolone sulfate and (+)-pentazocine. These effects, albeit opposite in direction, were blocked by both the 21-mer antisense oligodeoxynucleotide and pertussis toxin. Western blotting indicates that sigma(1)-receptors are increased on the plasma membrane and the nuclear membrane in the presence of sigma(1)-ligand. These results suggest that Ca(2+) signaling via sigma(1)-receptors may represent a novel mechanism that affects intracellular Ca(2+) concentrations.
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PMID:Ca(2+) signaling via sigma(1)-receptors: novel regulatory mechanism affecting intracellular Ca(2+) concentration. 1086 77


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