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)

The authors studied the biological properties of the preparations of pertussis protective antigens obtained by the disintegration of the microbial mass of Bordetella pertussis, with the subsequent purification with trichloracetic acid (TCA-preparations). TCA-preparations proved to possess a stable protective activity and by the ratio of the protective dose to toxic and histamine-sensitizing doses considerably exceeded the corpuscular vaccine. A TCA-preparation fraction with a greater immunogenic activity than the initial preparation was obtained by chromatography on sepharose 4B.
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PMID:[Immunogenicity and toxicity of soluble trichloroacetic acid precipitate from pertussis microbes and its fractions]. 20 17

Certain microbial toxins are ADP-ribosyltransferases, acting on specific substrate proteins. Although these toxins have been of great utility in studies of cellular regulatory processes, a simple procedure to directly study toxin-catalyzed ADP-ribosylation in intact cells has not been described. Our approach was to use [2-3H]adenine to metabolically label the cellular NAD+ pool. Labeled proteins were then denatured with SDS, resolved by PAGE, and detected by flurography. In this manner, we show that pertussis toxin, after a dose-dependent lag period, [3H]-labeled a 40-kD protein intact cells. Furthermore, incubation of the gel with trichloroacetic acid at 95 degrees C before fluorography caused the release of label from bands other than the pertussis toxin substrate, thus, allowing its selective visualization. The modification of the 40-kD protein was ascribed to ADP-ribosylation of a cysteine residue on the basis of inhibition of labeling by nicotinamide and the release of [3H]ADP-ribose from the labeled protein by mercuric acetate. Cholera toxin catalyzed the [3H]-labeling of a 46-kD protein in the [2-3H]adenine-labeled cells. Pretreatment of the cells with pertussis toxin before the labeling of NAD+ with [2-3H]adenine blocked [2-3H]ADP-ribosylation catalyzed by pertussis toxin, but not that by cholera toxin. Thus, labeling with [2-3H]adenine permits the study of toxin-catalyzed ADP-ribosylation in intact cells. Pasteurella multocida toxin has recently been described as a novel and potent mitogen for Swiss 3T3 cell and acts to stimulate the phospholipase C-mediated hydrolysis of polyphosphoinositides. The basis of the action of the toxin is not known. Using the methodology described here, P. multocida toxin was not found to act by ADP-ribosylation.
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PMID:A novel approach to detect toxin-catalyzed ADP-ribosylation in intact cells: its use to study the action of Pasteurella multocida toxin. 183 59

Pertussis toxin (PT), preactivated with 20 mm dithiothreitol (DTT), was incubated with different serum dilutions (1/10-1/200) before addition to the reaction mixture. Final concentrations of the reagents were: PT (50 ng/ml), dithiothreitol (DTT)(less than or equal to 0.3 mM), bovine transducin (2 micrograms/ml), ATP (1 mM). GTP (1 mM), lysophosphatidylcholine (LTC) (0.1 mg/ml), sodium acetate (NaAc) (0.1 M), Tris-HCl, pH 7.1 (0.06 M) and 32P-NAD+ (10 microCi 28 Ci/mM). The reaction was stopped by precipitation with 10% TCA (w/v), the pellet was collected and the samples were submitted to SDS-PAGE followed by autoradiography. ADP-ribosylation was detected as the radiolabelling of a protein band (m.w. approximately 40 kD) corresponding to the alpha-subunit of transducin. 32P-ADP incorporation was a linear function of PT concentration. By this assay quantitative differences in PT neutralizing antibodies were found between sera which were not revealed by measuring PT neutralizing antibodies by a Chinese hamster ovary (CHO) cell culture test or by an enzyme-linked immunosorbent assay (ELISA). The conditions of the ADP-ribosylation of bovine transducin have been optimized to permit detection of the enzymic activity of as low amounts of PT as 0.5 ng. This opens the possibility of the study of the presence and avidity of neutralizing antibodies to PT in post-vaccination sera without preceding purification and concentration of the antibodies and thus may provide a useful tool for evaluation of whooping cough vaccines.
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PMID:A sensitive method for measuring neutralizing antibodies to Bordetella pertussis toxin: optimized ADP-ribosylation of transducin. 204 77

B. pertussis protein fraction obtained by precipitation with trichloroacetic acid (TCA) stimulated the development of clinically and histologically pronounced experimental allergic encephalomyelitis (EAE) in guinea pigs when introduced together with a heterologous cerebral antigen, the two compounds forming an encephalitogenic mixture. The adjuvant activity of the TCA-precipitated fraction depended on its dose. The sera of the animals with EAE induced by the encephalitogenic mixture containing B. pertussis cells or TCA-precipitated fraction showed a cytopathogenic effect in the monolayer culture of newborn rat cerebellum cells. The cytopathogenic effect was more pronounced in the sera obtained at the period of the development of the clinical symptoms of the disease (days 14-18), while the cytotoxic effect of the sera obtained on day 30 after immunization decreased irrespective of the manifestations of EAE, this decrease being in correlation with the dose of the TCA-precipitated fraction in the encephalitogenic mixture.
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PMID:[Role of the protein fraction of Bordetella pertussis in inducing experimental allergic encephalomyelitis]. 630 Nov 73

The mechanisms by which somatostatin exerts its widespread inhibitory actions have been investigated extensively but understood only partially. Recent studies have shown that somatostatin can inhibit gene transcription directly. In view of the critical importance of early response genes in induction of gene expression, we examined whether the action of somatostatin might be mediated by inhibition of early response genes. The products of some of these genes, such as c-fos and c-jun, are known to form a heterodimeric transcription factor complex (AP-1) that binds specifically to the consensus sequence TGAC(G)TCA. Accordingly, we examined the effects of somatostatin on c-fos gene expression and on the binding of the AP-1 complex to its specific DNA element using isolated gastric parietal cells and the GH3 pituitary cell line. In both parietal and GH3 cells, c-fos-specific mRNA was increased by agents known to act via both adenosine-3',5'-cyclic monophosphate and Ca(2+)-dependent signaling mechanisms, and octreotide significantly inhibited this response. Pertussis toxin pretreatment (200 ng/ml) reversed the inhibitory effect of octreotide. AP-1 binding activity, assessed by gel shift assays using a 32P-labeled AP-1 oligonucleotide probe, was stimulated by dibutyryl adenosine 3',5'-cyclic monophosphate and serum and inhibited by octreotide treatment. Our observations support the notion that the universal inhibitory action of somatostatin may be mediated by inhibition of expression of early response genes via a pertussis toxin-sensitive inhibitory pathway. This effect appears to lead to decreased binding of regulatory nuclear proteins to their specific DNA elements resulting, presumably, in diminished gene expression.
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PMID:Molecular basis for somatostatin action: inhibition of c-fos expression and AP-1 binding. 791 96

Hamster tracheal epithelial cell cultures were used to investigate muscarinic regulation of high-molecular-weight glycoconjugate (HMWG) secretion by airway goblet cells. HMWG were radiolabeled with N-acetyl-D-[1-(3)H]glucosamine, precipitated with trichloroacetic acid and phosphotungstic acid, and counted by liquid scintillation. Carbachol (100 microM) increased HMWG secretion (166.6 +/- 18.7%, P < 0.001, n = 20), and this response was blocked by the muscarinic receptor antagonist atropine. Ca2+ may not be essential for carbachol response since 1) carbachol-activated secretion was not inhibited by chelating extracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or by reducing both extracellular and intracellular Ca2+ with BAPTA-acetoxymethyl ester in low-Ca2+ medium; 2) the carbachol response was only partially blocked in low-Ca2+ medium; and 3) calcium ionophore did not stimulate HMWG secretion. However, carbachol-stimulated secretion was abolished by pertussis toxin (PTX), indicating the involvement of a PTX-sensitive guanine nucleotide-binding regulatory protein (G protein), and by the protein kinase C (PKC) inhibitor chelerythrine chloride. Furthermore, carbachol-stimulated secretion was not inhibited by overnight incubation with phorbol 12-myristate 13-acetate. In conclusion, carbachol-stimulated secretion of HMWG appears to be coupled to a PTX-sensitive G protein and requires the activation of a phorbol ester-insensitive PKC isoform.
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PMID:Muscarinic-induced mucin secretion and intracellular signaling by hamster tracheal goblet cells. 912 73

Chemokine receptor-like 1 (CKR-L1) was described recently as a putative seven-transmembrane human receptor with many of the structural features of chemokine receptors. To identify the ligand of CKR-L1, we have studied chemokine-induced calcium mobilization in 293 cells transfected with CKR-L1. Of 20 different chemokines tested, only I-309 was able to elicit a significant calcium mobilization. In addition, I-309 induced the transfectants to migrate in vitro. As expected for chemokine receptor-mediated effects, pertussis toxin, but not cholera toxin, inhibited both the calcium flux and migration of the CKR-L1 transfectants in response to I-309. All of these data support the conclusion that I-309 is a functional ligand for CKR-L1. According to the current chemokine receptor nomenclature, we have designated this gene as CCR8. The murine CCR8 (mCCR8) gene was cloned, and its predicted amino acid sequence showed a 71% identity with that of human CCR8. As human CCR8, mCCR8 is expressed in thymus. Both I-309 and its murine homologue TCA-3 were able to induce calcium mobilization in transiently transfected 293-EBNA cells expressing mCCR8. The affinity of the binding of 125I-labeled TCA-3 to mCCR8 was high (Kd approximately 2 nM); the binding was prevented completely by an excess of cold TCA-3, and only partially competed (40%) by I-309. The identification of I-309 and TCA-3 as the functional ligands for CCR8 receptors will help to unravel the role of these proteins in physiologic and pathologic situations.
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PMID:Identification of CCR8 as the specific receptor for the human beta-chemokine I-309: cloning and molecular characterization of murine CCR8 as the receptor for TCA-3. 946 61

Chemokines have been hypothesized to contribute to the selectivity of lymphocyte trafficking not only as chemoattractants, but also by triggering integrin-dependent sticking (arrest) of circulating lymphocytes at venular sites of extravasation. We show that T cells roll on most Peyer's patch high endothelial venules (PP-HEVs), but preferentially arrest in segments displaying high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine, Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is selectively inhibited by functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and for macrophage inflammatory protein (MIP)-3beta (EBV-induced molecule 1 ligand chemokine [ELC]), and does not occur in mutant DDD/1 mice that are deficient in these CCR7 ligands. In contrast, pertussis toxin-sensitive B cell sticking does not require SLC or MIP-3beta signaling, and occurs efficiently in SLC(low/-) HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, sites of T and B cell firm adhesion are segregated in PPs, with HEVs supporting B cell accumulation concentrated in or near follicles, the target domain of most B cells entering PPs, whereas T cells preferentially accumulate in interfollicular HEVs. Our findings reveal a fundamental difference in signaling requirements for PP-HEV recognition by T and B cells, and describe an unexpected level of specialization of HEVs that may allow differential, segmental control of lymphocyte subset recruitment into functionally distinct lymphoid microenvironments in vivo.
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PMID:The role of chemokines in the microenvironmental control of T versus B cell arrest in Peyer's patch high endothelial venules. 1062 Jun 6

The regulation of glycogen synthase activity by bile acids in primary hepatocytes and in the intact liver was investigated. Bile acids (deoxycholic acid, DCA; taurocholic acid, TCA) activated AKT and glycogen synthase (GS) in primary rat hepatocytes. Incubation with a phosphatidyl inositol-3 kinase inhibitor or expression of dominant-negative AKT in primary rat hepatocytes abolished activation of AKT and GS by DCA and TCA. TCA, but not DCA, activated Galpha(i) proteins in primary rat hepatocytes. Treatment of cells with pertussis toxin or expression of dominant-negative Galpha(i) blocked TCA-induced activation of AKT and of GS but did not alter AKT or GS activation caused by DCA. TCA caused activation of AKT and GS in intact rat liver. Expression of dominant-negative Galpha(i) reduced TCA-induced activation of AKT and of GS in intact rat liver. Together, our findings demonstrate that bile acids are physiological regulators of glycogen synthase in rat liver and that conjugated bile acids use a Galpha(i)-coupled G protein-coupled receptor to regulate GS activity in vitro and in vivo.
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PMID:Conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and in vivo via Galphai signaling. 1720 Apr 18

A mathematical model based on a dynamic metabolic flux balance (DMFB) is developed for a process of fed-batch fermentation of Bordetella pertussis. The model is based on the maximization of growth rate at each time interval subject to stoichiometric constraints. The model is calibrated and verified with experimental data obtained in two different bioreactor experimental systems. It was found that the model calibration was mostly sensitive to the consumption or production rates of tyrosine and, for high supplementation rates, to the consumption rate of glutamate. Following this calibration the model correctly predicts biomass and by-products concentrations for different supplementation rates. Comparisons of model predictions to oxygen uptake and carbon emission rates measurements indicate that the TCA cycle is fully functional.
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PMID:A dynamic metabolic flux balance based model of fed-batch fermentation of Bordetella pertussis. 2322 86


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