UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fimbriae belong to a class of extracellular filamentous proteins which are involved in the attachment of bacteria to host tissues. Bordetella pertussis, the etiological agent of whooping cough, produces two serologically distinct fimbriae. We show that, like a number of other B. pertussis virulence genes, transcription of the fimbrial subunit genes (fim) is positively controlled by trans-acting polypeptides encoded by the bvg locus. In addition to this coordinate control, transcription of the fim genes is regulated at an individual level by phase variation. This process is characterized by a switching between a high and low level of expression of a particular fim gene. We have identified a conserved DNA region, located close to the start of the fim genes, which is likely to be involved in both positive regulation by the bvg locus, and phase variation. This promoter region contains a stretch of approximately 15 C residues and it appears that phase transitions occur by small insertions or deletions in this C-rich region. We propose that these mutations affect transcription of the fim genes by varying the distance between the binding site for an activator and the -10 box. The fim promoter shows homology with the pertussis toxin promoter, which is also positively regulated by the bvg locus.
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PMID:Fimbrial phase variation in Bordetella pertussis: a novel mechanism for transcriptional regulation. 197 38

We have identified four cDNA clones, cl-1, cl-5, cl-15, and cl-16, that represent genes induced by serum in resting mouse 3T3 cells. Partial sequence analysis of the four cDNAs indicated that cl-15 corresponds to the mouse beta-actin gene. Comparison of the DNA sequences of the other three clones with the sequence data bank (Genbank) showed little homology to other known DNA sequences and thus represent novel genes. The level of the mRNAs corresponding to the four genes began to increase in resting cells following serum stimulation, reached a peak between 5 h and 8 h and then started to decline. Inhibitors of transcription diminished the induction of the mRNAs corresponding to the four genes. Cycloheximide and anisomycin had little effect on the induction of beta actin mRNA while the induction of the other three genes was suppressed by the same inhibitors. 12-O-Tetradecanoylphorbol-13-acetate and the calcium ionophore A23187 enhanced the expression of the cl-16 mRNA while epidermal growth factor, fibroblast growth factor, or insulin enhanced the expression of cl-1- and cl-5-specific transcripts. The level of beta-actin mRNA was elevated in resting cells by epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate and to a lesser extent by fibroblast growth factor, insulin, and dibutyryl cyclic AMP-elevating agents. Pertussis toxin, an inhibitor of the action of G proteins, did not significantly suppress the activation of the four genes by serum. However, 2-aminopurine, a protein kinase inhibitor, suppressed the induction of the four transcripts in serum-stimulated cells. The possible pathways involved in the activation of these genes in resting cells are discussed.
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PMID:Identification and partial characterization of genes that are transactivated by different pathways in quiescent mouse cells stimulated with serum. 197 37

Acetylcholine (ACh) can inhibit calcium currents (ICa) in nerve cells by activating muscarinic ACh receptors (mAChR). There are several different genetic subtypes of mAChR. It is not known which subtype(s) are responsible for ICa inhibition. To resolve this issue, we measured ICa inhibition by ACh with patch-clamp recording, by using Ba2+ as charge carrier, in clones of NG108-15 neuroblastoma x glioma hybrid cells transfected with DNA for mAChRI, II, III and IV. Control (non-transfected) cells showed a mean maximum inhibition of peak ICa of 12.8 +/- 1.8% (n = 36) at 1 mM ACh. No consistent increase in inhibition was detected in vector-transfected cells, or in cells transformed to express mAChRI or mAChRIII. In contrast, inhibition was significantly increased in clones transformed to express mAChRII or mAChRIV. Inhibition was not correlated with the number of muscarinic receptors as determined by 3H-quinuclidinyl benzilate binding. Inhibition in both control and transfected cells was prevented by pretreatment with pertussis toxin (PTx). Inhibition persisted in the presence of extracellular or intracellular dibutyryl cyclic AMP, and hence is not because of inhibition of adenylate cyclase. We conclude that the inhibition of neuronal ICa is mediated preferentially by mAChRII and mAChRIV, via a PTx-sensitive GTP-binding protein.
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PMID:Selective coupling of different muscarinic acetylcholine receptors to neuronal calcium currents in DNA-transfected cells. 198 Jul 42

To test the hypothesis that agents activating receptors negatively coupled to adenylyl cyclase (AC) can stimulate cell proliferation, we have expressed a human alpha 2-adrenergic receptor (alpha 2-C10) in CCL39 cells and studied the effects of alpha 2-agonists on reinitiation of DNA synthesis in quiescent cells. We report that the alpha 2-agonists epinephrine and clonidine stimulate [3H]-thymidine incorporation in synergy with fibroblast growth factor and that the alpha 2-antagonist yohimbine efficiently inhibits this response. Epinephrine- and clonidine-stimulated DNA synthesis is completely blocked by pertussis toxin and correlates well with the inhibition of prostaglandin E1-stimulated AC. Thus, their action closely resembles the action of serotonin in the same cell system, which is mediated through 5-HT1b receptors. In fact, serotonin- and epinephrine-stimulated DNA synthesis reinitiation is not additive, suggesting that both agents act through a common pathway. Interestingly, alpha 2-agonists also induced a moderate release of inositol phosphates, indicating that alpha 2-adrenergic receptors can interact both with the AC and phospholipase C messenger system. Activation of phosphoinositide (PI) turnover by epinephrine leads to a significant stimulation of Na+/H+ exchange but is insufficient to trigger a mitogenic response in CCL39 cells, as will be discussed. We found no evidence for epinephrine-induced activation of Na+/H+ exchange by a mechanism independent of PI breakdown.Our data show that alpha 2-adrenergic receptors can play a role in the regulation of cell proliferation in an appropriate context; also, the data support the hypothesis that receptors negatively coupled to AC must be taken into account as mediators of growth factor action in fibroblasts, in particular when activated in parallel with receptor tyrosine kinases.
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PMID:Alpha 2-adrenergic agonists stimulate DNA synthesis in Chinese hamster lung fibroblasts transfected with a human alpha 2-adrenergic receptor gene. 198 85

In BALB/c 3T3 cells pretreated with platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) (primed-competent cells), insulin-like growth factors I and II (IGF-I and IGF-II) bind to their own receptors (IGF-IR and IGF-IIR) and stimulate calcium influx and DNA synthesis by a mechanism involving a 40-kDa pertussis toxin substrate. In contrast, these IGFs do not act on unprimed quiescent cells. In this study, the 40-kDa pertussis toxin substrate was identified as Gi-2 alpha using anti-G protein antibodies. We analyzed the quality of signal transduction from IGF-II to Gi-2 alpha. There was no difference in the amount of Gi-2 alpha between quiescent and primed-competent cells, and both of these cells had similar Kd values and numbers of IGF-II-binding sites. Whereas IGF-II did not alter pertussis toxin-catalyzed ADP-ribosylation of Gi-2 alpha in quiescent cells, IGF-II reduced the pertussis toxin substrate activity by 35-50% via the IGF-IIR in primed-competent cells. The action of IGF-II lasted for up to 3 h when IGF-II was present in the medium, and it disappeared when IGF-II was removed. These results suggest that the signaling pathway triggered by IGF-II is uncoupled between the IGF-IIR and Gi-2 alpha in quiescent cells and that PDGF and EGF restore the IGF-IIR-Gi-2 coupling. This study also indicates that low concentrations of IGF-I reduce the pertussis toxin substrate activity of Gi-2 alpha in primed-competent cells in a time course slower than that of IGF-II, but not at all in quiescent cells. However, both of these cells had similar Kd values and numbers of IGF-I binding sites. Therefore, the IGF-I signaling pathway may also be uncoupled between the IGF-IR and Gi-2 alpha in quiescent cells and restored by PDGF and EGF. In BALB/c 3T3 cells transfected with temperature-sensitive Kirsten sarcoma virus bearing the v-Ki-ras gene (ts cells), a 40-kDa pertussis toxin substrate was also identified as Gi-2 alpha. In nonpermissive ts cells, IGF-II was without effect on the pertussis toxin substrate activity of Gi-2 alpha or on calcium influx.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of transmembrane signal transduction of insulin-like growth factor II by competence type growth factors or viral ras p21. 198 36

Adenylate cyclase (AC) toxin from B. pertussis enters eukaryotic cells where it produces supraphysiologic levels of cAMP. Purification of AC toxin activity [(1989) J. Biol. Chem. 264, 19279] results in increasing potency of hemolytic activity and electroelution of the 216-kDa holotoxin yields a single protein with AC enzymatic, toxin and hemolytic activities. AC toxin and E. coli hemolysin, which have DNA sequence homology [(1988) EMBO J. 7, 3997] are immunologically cross-reactive. The time courses of hemolysis elicited by the two molecules are strikingly different, however, with AC toxin eliciting cAMP accumulation with rapid onset, but hemolysis with a lag of greater than or equal to 45 min. Finally, osmotic protection experiments indicate that the size of the putative pore produced by AC toxin is 3-5-fold smaller than that of E. coli hemolysin.
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PMID:Hemolytic activity of adenylate cyclase toxin from Bordetella pertussis. 199 77

To assess antibody and cellular immune responses, 156 healthy children were immunized at approximately 18 months of age with acellular diphtheria-tetanus-pertussis vaccine. Changes in antibody responses to filamentous hemagglutinin (FHA) and to pertussis toxin (PT) were similar in pattern, and antibody titers reached values equal to those from patients with convalescent-stage pertussis. The FHA-induced DNA synthesis in peripheral blood mononuclear cells was maximum at 4 weeks after the primary series, and these levels were equal to those of patients with pertussis. High amounts of PT-induced DNA synthesis were observed in both immunized and nonimmunized children; thus, PT seemed to act mainly as a nonspecific mitogen. Almost the same responses to several mitogens that activate different subsets of lymphocytes were observed in young infants compared with older children. Furthermore, young infants who had Bordetella pertussis infection responded by FHA stimulation almost as well as older children.
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PMID:Immune responses to Bordetella pertussis infection and vaccination. 199 29

Transcription of numerous virulence genes in Bordetella pertussis is positively regulated by the products of the bvgAS genes. In this study a series of lacZYA fusions containing deletions in either the fhaB or bvgA promoter regions was used to identify cis-acting regulatory regions required for bvg activation of these two genes. Gel retardation and DNase I protection analyses have shown that specific protein-DNA interactions occur at these regulatory regions and that these interactions require the transcriptional activator protein BvgA. The regulatory regions found upstream of fhaB and bvgA which are involved in protein binding both contain the sequence TTTCCTA. This sequence is part of an inverted repeat upstream of fhaB and a direct repeat upstream of bvgA. Homologous repeats are not apparent upstream of other bvg-activated genes, such as ptx and cyaA. These data suggest that the mechanism for transcriptional regulation of the other bvg-activated genes is complex and may require regulatory factors in addition to the bvgAS gene products.
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PMID:Identification of Bordetella pertussis regulatory sequences required for transcriptional activation of the fhaB gene and autoregulation of the bvgAS operon. 200 57

We recently reported that extracellular ATP was mitogenic for Swiss 3T3, 3T6, and A431 cells (Huang et al.: Proc. Natl. Acad. Sci. USA, 86:7904-7908, 1989). Here we examined the possible involvement of activation of the protein kinase C (PKC) signal transduction pathway in the mechanism of action of extracellular ATP. A potent synergistic stimulation of DNA synthesis in quiescent cultures of 3T3 and 3T6 cells was observed when ATP was presented in combination with growth factors that activate PKC, such as bombesin, vasopressin, or tumor-promoting phorbol esters. This finding suggests that ATP and these mitogens do not act through a common mechanism. In contrast, ATP was unable to show synergism with phorbol esters in A431 cells. We discovered striking differences when we examined the kinetics of formation of diacylglycerol (DAG) stimulated by ATP among these cell lines. Thus, ATP stimulated a sustained biphasic increase of DAG in A431 cells, but only a rapid transient increase of DAG formation was observed in 3T3 and 3T6 cells. The breakdown of phosphatidylcholine was stimulated by ATP in A431 cells; however, a significantly reduced effect was displayed in 3T6 cells. Furthermore, we found that the diacylglycerol-kinase inhibitor, 1-monooleoylglycerol, greatly potentiated ATP-stimulated DNA synthesis in A431 cells. Finally, down-regulation of PKC by long-term exposure to phorbol dibutyrate (PDBu) prevented stimulation of DNA synthesis induced by bombesin, vasopressin, or phorbol esters in 3T3 or 3T6 cells, while it had no such effect on ATP-stimulated mitogenesis in the presence of insulin or epidermal growth factor. On the other hand, PDBu-mediated down-regulation of PKC partially inhibited [3H [thymidine incorporation stimulated by ATP in A431 cells. Taken together, we conclude that a protein kinase C-dependent pathway is partially involved in ATP-stimulated DNA synthesis in A431 cells, but a protein kinase C-independent pathway exists in 3T3 and 3T6 cells. Pertussis toxin (PTX) inhibited the sustained phase of DAG formation and the breakdown of phosphatidylcholine stimulated by ATP in A431 cells. This suggests involvement of a PTX-sensitive G protein.
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PMID:Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: I. Involvement of protein kinase C-dependent and -independent pathways. 202 2

The gene prn encoding the outer-membrane protein P.70 (pertactin) from Bordetella parapertussis has been cloned in Escherichia coli and its DNA sequence determined. Analysis of the DNA sequence reveals that the gene has an open reading frame comprising 922 amino acids capable of encoding a protein with a molecular weight of 95,177 (P.95). In vivo processing of this precursor yields a protein with an estimated Mr of 70 kDa (P.70) which is located on the surface of B. parapertussis. Homology between the prn gene from B. parapertussis and that from Bordetella pertussis is 91.3%. The homology is 93% when the protein sequence of P.95 is aligned with that of P.93 from B. pertussis. The major differences between the P.70 pertactin from B. parapertussis and the P.69 pertactin from B. pertussis occur in the number of reiterated units within the repeat motifs found in both proteins; the sequence Gly-Gly-Xaa-Xaa-Pro is repeated four times in the P.70 pertactin, and five times in the P.69 pertactin, while the sequence Pro-Gln-Pro occurs nine times in P.70 pertactin and five times in P.69 pertactin. Cloning of the gene for P.95 in an E. coli expression vector results in the synthesis of a protein that mimics native gene expression in B. parapertussis, i.e. the P.95 protein is synthesized and subsequently processed to yield the P.70 form of the protein on the surface of the cell.
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PMID:P.70 pertactin, an outer-membrane protein from Bordetella parapertussis: cloning, nucleotide sequence and surface expression in Escherichia coli. 204 76

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