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)

1. Somatotrophs were obtained from rat pituitary glands after dissociation, separation and enrichment on a continuous gradient of bovine serum albumin at unit gravity. Somatotrophs were enriched up to 85% in the heavy fractions (F8 and F9). 2. After identification by reverse hemolytic plaque assay, patch-clamp recording in the whole-cell mode was performed on somatotrophs. 3. Under voltage-clamp conditions, two types of Ca2+ currents were recorded. From a holding potential of -70 mV, depolarizing voltage steps to potentials more positive than -50 mV activated a current which rapidly inactivated and which was very sensitive to Ni2+ but not to Cd2+. This current corresponds to T-type current. Depolarizing steps to potentials more positive than -30 mV from a holding potential of -40 mV triggered a current which slowly inactivated and which was very sensitive to Cd2+ but not to Ni2+. This current corresponds to L-type current. 4. Application of somatostatin to the bath solution (10 nM) markedly reduced the amplitudes of both T- and L-type currents. Somatostatin decreased the conductance of L-type current without modifying its time- and voltage-dependent inactivation but its activation was not affected. However, somatostatin decreased the conductance of T-type currents, and also accelerated its time-dependent inactivation. Half-inactivation voltage of T-type current was shifted from -52 to -63 mV by somatostatin but no change was obtained in the current activation curve. 5. All these modifications in Ca2+ currents were abolished by a pre-treatment of the cultures with pertussis toxin (100 ng/ml, for 10 h). This pre-treatment also blocked the inhibitory effect of somatostatin on high-K(+)-stimulated growth hormone release. 6. Our results show that somatostatin acts on somatotrophs by attenuating the voltage-dependent Ca2+ currents. These effects may contribute to a somatostatin-induced reduction in [Ca2+]i and the subsequent decline in growth hormone release.
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PMID:Two types of voltage-dependent calcium current in rat somatotrophs are reduced by somatostatin. 197 2

Our previous study demonstrated that cataract Shionogi (CTS) mice, an inbred strain related to non-obese diabetic (NOD) mice, are T lymphocytopenic and that their T cell-mediated in vitro reactions, such as proliferative responses of spleen cells to T cell mitogens and alloantigens or production of IL 2 and IL 2 receptors after stimulation of spleen cells with Con A, are greatly reduced. To confirm these in vitro characteristics, in vivo immune responses of CTS mice to T-dependent and T-independent antigens were compared with those of some reference strains including NOD mice. Antibody responses of CTS mice after one injection of a high dose (10(8)) or one or two injections of a low dose (10(5)) of sheep red blood cells (SRBC) were markedly lower than those of the reference strains. The decrease was particularly striking in the IgM antibody production at primary response to both high and low doses, and the IgG antibody production at the secondary response to low dose. Similar lower antibody production was observed in CTS mice against bovine serum albumin (BSA). Little production of IgE antibody was observed from 1 through 3 weeks after an injection of BSA plus Bordetella pertussis. IgG1 response was observed at high incidence but lower in titer than those in the reference strains. Unexpectedly, in spite of the poor antibody production to BSA, potent systemic sensitization for anaphylactic shock was easily established; incidence of lethal shock being comparable with those in the reference strains. This suggests that CTS mice are highly susceptible to the effector phase of active anaphylactic shock. Cell-mediated immunity was also impaired. Delayed type of hypersensitivity to SRBC was low, and the rejection of the skin graft from NOD mouse did not occur. In contrast to the reduced T cell-mediated responses, no difference was found between CTS and reference strains with regard to the antibody production to LPS, a T-independent antigen. These in vivo findings are consistent with the previous in vitro study.
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PMID:Immune deficiency of cataract Shionogi (CTS) mouse. II. Impaired in vivo T cell-mediated immune response. 207 15

Bordetella pertussis TOX3201 has a 12-base-pair insertion in the S1 subunit gene of pertussis toxin (PTX), which encodes for a 4-amino-acid insertion between residues 107 and 108 of the mature S1 subunit (Black et al., Science 240:656-659, 1988). This mutant strain has been shown to secrete a holotoxin analog of PTX, designated CRM3201, with reduced ADP-ribosyltransferase activity. In the present study, we evaluated the biochemical, biological, and immunoprotective activities of purified CRM3201. Assay of enzymatic activities showed that CRM3201 had 20 to 30% of the ADP-ribosyltransferase activity and 55 to 60% of the NAD glycohydrolase activity of native PTX. CRM3201, however, had only 2 to 6% of the activity of PTX in clustering CHO cells, promoting leukocytosis, inducing histamine sensitization, and potentiating an anaphylactic response to bovine serum albumin. In contrast, activities associated with the B oligomer (binding to fetuin, hemagglutination of goose erythrocytes, and lymphocyte mitogen activity) were comparable to those of native PTX. Injection of BALB/c mice with CRM3201 mixed with Al(OH)3 elicited high titers of antibody to PTX (as measured by enzyme-linked immunosorbent assay), which neutralized a leukocytosis-promoting dose of PTX in these mice and neutralized PTX in a CHO cell assay. Passive transfer of the anti-CRM3201 antibody protected 20-day-old Swiss-Webster mice against a lethal aerosol challenge with B. pertussis 18323. Active immunization with CRM3201 significantly reduced lung colonization in adult BALB/c mice with a B. pertussis respiratory infection. These results demonstrate (i) that the reduced ADP-ribosyltransferase activity of CRM3201 is associated with reductions in certain biological and toxic activities of PTX (the enzymatic and biological activities are not, however, totally concordant); (ii) that CRM3201 possesses a functional B oligomer; and (iii) that CRM3201 can induce toxin-neutralizing antibodies which protect mice against a respiratory challenge with B. pertussis. Our studies with CRM3201 show that recombinant analogs of PTX have the potential to be developed into safe, protective immunogens for use in new acellular pertussis vaccines.
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PMID:Pertussis toxin analog with reduced enzymatic and biological activities is a protective immunogen. 211 44

Two peptides, corresponding to amino acids 1-17 and 169-186 of the amino acid sequence of pertussis toxin (PT) subunit S1, were synthesized and coupled to the diphtheria toxin cross-reactive mutant protein CRM 197 and evaluated for immunogenicity and protective capacity against PT challenge in vivo. The peptide-CRM conjugates induced high antibody titers against native toxin in mice (BALB/c, C57/Black, and outbred NMRI) as measured by ELISA. Upon PT challenge (0.5 microgram of toxin) of the NMRI mice, the CRM conjugates of peptides 1-17 and 169-186 fully protected the mice from PT-induced leukocytosis. Immunization with the corresponding bovine serum albumin conjugates of these two peptides also fully protected mice. Rabbit antiserum to the peptide 1-17-CRM conjugate was highly efficient in inhibiting the ADP-ribosylating activity of PT but did not neutralize the clustering effect of PT on Chinese hamster ovary cells. In contrast, the rabbit antiserum raised against the peptide 169-186-CRM conjugate neutralized the clustering effect of PT on Chinese hamster ovary cells but did not inhibit the enzymatic activity of PT. Peptide 169-186-CRM conjugates mimic the immunoglobulin binding properties of PT and also cause clustering of Chinese hamster ovary cells. The CRM conjugates of these two peptides constitute a synthetic pertussis vaccine candidate with the ability to provide a chemically well-defined, safe, and efficient pertussis vaccine.
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PMID:Protective immunogenicity of two synthetic peptides selected from the amino acid sequence of Bordetella pertussis toxin subunit S1. 230 2

The anti-human serum albumin (HSA) B-cell repertoire of C57BL/6 mice was examined by culturing splenocytes at limiting dilution following polyclonal stimulation with Escherichia coli lipopolysaccharide and a lymphokine mixture. The frequency of anti-HSA precursors was determined before and after immunization with alum-precipitated HSA and 10(9) killed Bordetella pertussis organisms, by submitting clonal supernatants to an ELISA. Anti-HSA IgG1-forming precursors were rare in unimmunized spleens, representing approximately equal to 1 in 500,000 splenocytes or only approximately equal to 100 cells per spleen. Between day 5 and day 7 after immunization, this figure increased to approximately equal to 20,000 cells per spleen. Over the following 3 weeks, there was a progressive increase in the mean optical density generated in the clonal ELISA, presumably due to affinity maturation of the B-cell population. When freshly deaggregated HSA was injected before or even up to 4 days after challenge immunization, the appearance of anti-HSA IgG1-forming cell precursors was largely prevented. The effect was most marked with 5 mg or 1 mg of soluble HSA, but impressive partial effects could be seen with as little as 10 micrograms of HSA if administered before challenge immunization. Most of the few clones seen after the higher doses of the toleragen appeared to make antibody of low affinity. The capacity to influence the B-cell pool by soluble antigen administered just 1-2 days before the sudden appearance of IgG1 precursors argues against the totality of the effect being due to T-cell-mediated suppression and in favor of a direct effect on B cells.
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PMID:Soluble antigen abrogates the appearance of anti-protein IgG1-forming cell precursors during primary immunization. 230 21

WBB6F1 mouse, a mast cell-deficient strain, was tested for active and passive cutaneous anaphylactic reactions. Active cutaneous anaphylaxis was not produced in mice which had been immunized for 1 to 2 weeks by an intraperitoneal injection of bovine serum albumin with either adjuvant, Freund's complete adjuvant or Bordetella pertussis organisms, even though circulatory IgE and IgG1 antibodies were raised. Passive cutaneous anaphylaxis (PCA) was also absent, when the mice had been sensitized with allogeneic IgE or IgG1 monoclonal antibodies. However, obvious PCA was produced when allogeneic or xenogeneic hyperimmune serum was employed. These findings indicate that mast cells are not necessarily needed for the production of PCA. Some mechanism quite different from the well-elucidated mechanism, i.e., IgE- or IgG1 antibody-triggered histamine release from mast cells, seems to be operative.
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PMID:Active and passive cutaneous anaphylaxis in WBB6F1 mouse, a mast cell-deficient strain. 236 26

We synthesized six peptides (15-22 amino acids) from the amino acid sequence of the S1 subunit of pertussis toxin. The antigenicity of the polypeptides was investigated by enzyme-linked immunosorbent assays, in which the polypeptides coupled to bovine serum albumin were used as coating antigens. The polypeptides were examined as antigens for reaction with pre- and postvaccination sera from infants receiving either a Bordetella pertussis whole-cell vaccine or a vaccine containing pertussis toxoid. An elevated serum titer was noted upon vaccination with both types of vaccines when bovine serum albumin conjugates of five synthetic peptides were used as antigens. Similarly, mice immunized with whole-cell pertussis vaccine showed an elevated titer against all five peptides that were reactive with human sera. Thus, we identified five peptide sequences of S1 against which, in two species, antibodies are formed upon exposure of these species to whole cells of B. pertussis.
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PMID:Use of synthetic peptides to map antigenic sites of Bordetella pertussis toxin subunit S1. 245 Jan 53

This study examines the mechanism of guanine nucleotide-binding protein (G protein) coupling of receptors to phospholipase C. The Xenopus oocyte has a muscarinic receptor-activated Cl- current that is mediated by inositol 1,4,5-trisphosphate. Modulation of the muscarinic receptor-evoked Cl- current was examined under voltage clamp in oocytes injected with resolved G-protein subunits. The presence of an alpha subunit of G proteins in oocytes was shown by pertussis toxin-labeling of a 41-kDa band in oocyte membranes. The presence of the beta subunit of G proteins was demonstrated by immunoblotting experiments with an antiserum (U-49) that is specific for the beta subunit. Pertussis toxin treatment of oocytes resulted in the uncoupling of muscarinic receptors from activation of the Cl- current. Cells microinjected with 1.5 ng of human erythrocyte beta gamma-subunit complex or 1.0 ng of bovine brain beta gamma-subunit complex showed approximately a 95% reduction in the evoked Cl- current. Cells injected with equal volumes of protein storage vehicle showed no change in response. Cells injected with boiled beta gamma subunits, bovine serum albumin, or resolved alpha subunits also showed no reduction in response. Cells injected with various concentrations of beta gamma subunits showed a concentration dependence with half-maximal inhibition of the muscarinic activated Cl- current at about 10 nM. Cells injected with 1.0 ng of bovine brain beta gamma subunits could not respond to bath-applied agonist but could generate the Cl- current on intracellular injection of inositol 1,4,5-trisphosphate. These observations suggest that there is a G protein responsible for muscarinic receptor-mediated signal transduction through phospholipase C and that it is an alpha beta gamma heterotrimer. It appears that the mode of action of the G protein in the phospholipase C system may be similar to that of the hormone-activated adenylyl cyclase.
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PMID:Beta gamma subunits of GTP-binding proteins inhibit muscarinic receptor stimulation of phospholipase C. 246 57

The linear immunogenic and antigenic structure of the S2 subunit of pertussis toxin was investigated with synthetic peptides corresponding to regions of the protein sequence predicted to contain surface-exposed hydrophilic beta turns. Five peptides as peptide-bovine serum albumin conjugates were recognized by anti-pertussis toxin antiserum and were thus designated "immunogenic epitopes." Two prominent immunogenic epitopes were specified by peptides corresponding to sequences spanning R107-120 and R186-199, whereas peptides corresponding to residues R35-50 and R91-106 were only bound in low titer. Three peptides as thyroglobulin conjugates elicited antisera in rabbits that bound intact pertussis toxin by enzyme-linked immunosorbent assay and immunoblot. These peptides were designated "antigenic epitopes." The most prominent antigenic determinant was localized to the N-terminal end of the S2 sequence encompassing residue R1-7. Peptides R35-50 and R91-106 represented two minor antigenic epitopes. Antisera to two additional peptides corresponding to residues R134-149 and R186-199 recognized the S2 subunit only by Western blotting (immunoblotting). Only antiserum raised against peptide R91-106 also recognized the S3 subunit by Western blotting, indicating a marked antigenic and probably also structural difference between the two highly homologous subunits.
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PMID:Mapping of linear B-cell epitopes of the S2 subunit of pertussis toxin. 246 69

Chemosensitive sensory nerves have an important effector role in the control of vascular permeability in rat airways after neurogenic inflammation. To investigate whether they also have a role in antigen-induced lung inflammation, we have studied the changes in lung solute clearance (LSC) in sensitized rats after aerosol challenge with allergen and the effect of prior capsaicin-induced denervation on these changes. Sprague-Dawley rats were immunized with egg albumin (EA), using aluminum hydroxide and Bordetella pertussis as adjuvants. After 11 days, the animals were challenged for 5 min with aerosolized EA, and the clearance from the lungs of aerosolized 99mTc diethylenetriamine pentaacetic acid (99mTc-DTPA) over 7.5 min (LSC 7.5) was subsequently measured at various times after challenge as an index of epithelial permeability or integrity. Sensitized animals responded to the challenge with immediate respiratory symptoms and with an increased 99mTc-DTPA clearance rate that was detectable at 20 min (mean +/- SE LSC 7.5: baseline, 6 +/- 1%; 20 min, 17 +/- 3%; p less than 0.05), persisted at 4 h (14 +/- 1%; p less than 0.05), and returned to normal values after 24 h. Unsensitized rats exposed to EA and sensitized rats exposed to PBS or to bovine serum albumin did not show any change. Bronchoalveolar lavage failed to show significant changes of cell populations until 24 h, when an increased presence of lymphocytes, PMN, and eosinophils was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antigen-induced lung solute clearance in rats is dependent on capsaicin-sensitive nerves. 264 1


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