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 effects of the route of the injection and adjuvants on the immune response of guinea pigs were investigated at various stages of immune response to tetanus toxoid. Delayed-type hypersensitivity (DH) was observed as the first immune response to the toxoid before initiation of antitoxin production. The DH reaction was weak when plain toxoid was administered subcutaneously. Water-in-oil in water (w/o/w) enhanced greatly the reactivity of the immunized animals; pertussis vaccine, endotoxin and aluminium showed adjuvanticities in this order. The foot pad (fp) injection of plain toxoid promoted remarkably the induction of DH. The reactivity was enhanced considerably by w/o/w and to a less extent by aluminium. However, pertussis vaccine showed an adverse effect on DH by the fp route. Active cutaneous anaphylaxis (ACA) induced by the subcutaneous route was enhanced by w/o/w, endotoxin, pertussis vaccine and, to a less extent, by aluminium. The fp route compared with the sc route enhanced ACA by plain toxoid; w/o/w and aluminium but not endotoxin and the vaccine showed adjuvanticities. The influences of adjuvants and the route of injection on Arthus reactions were inconsistent. The effect of adjuvants on antitoxin production was quite different from that on DH when antitoxin was produced abundantly. Aluminium showed consistently a potent adjuvanticity, but activities of w/o/w, endotoxin and pertussis vaccine were inconsistent 4-6 weeks after the primary stimulus by the subcutaneous route. The adjuvant effect became less significant in the secondary response. The fp route was more favorable for antitoxin production than the subcutaneous route with most adjuvants except pertussis vaccine added to tetanus toxoid. Antitoxin production by plain toxoid was very poor when administered intraperitoneally; aluminium and w/o/w but not endotoxin showed a remarkable adjuvanticity for the antitoxin production.
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PMID:Studies on adjuvants for human prophylactics. II. Influence of the route of injection on the activity of adjuvants to tetanus toxoid in guinea pigs. 15 4

Guanyl nucleotide binding-proteins, or G-proteins, are ubiquitous molecules that are involved in cellular signal transduction mechanisms. Because a role has been established for cAMP in meiosis and G-proteins participate in cAMP-generating systems by stimulating or inhibiting adenylate cyclase, the present study was conducted to examine the possible involvement of G-proteins in the resumption of meiotic maturation. Cumulus cell-free mouse oocytes (denuded oocytes) were maintained in meiotic arrest in a transient and dose-dependent manner when microinjected with the nonhydrolyzable GTP analog, GTP gamma S. This effect was specific for GTP gamma S, because GppNHp, GTP, and ATP gamma S were without effect. Three compounds, known to interact with G-proteins, were tested for their ability to modulate meiotic maturation: pertussis toxin, cholera toxin, and aluminum fluoride (AlF4-). Pertussis toxin had little effect on maturation in either cumulus cell-enclosed oocytes or denuded oocytes when meiotic arrest was maintained with dibutyryl cAMP (dbcAMP) or hypoxanthine. Cholera toxin stimulated germinal vesicle breakdown (GVB) in cumulus cell-enclosed oocytes during long-term culture, but its action was inhibitory in denuded oocytes. AlF4- stimulated GVB in both cumulus cell-enclosed oocytes and denuded oocytes when meiotic arrest was maintained with hypoxanthine but was much less effective in dbcAMP-arrested oocytes. In addition, AlF4- abrogated the inhibitory action of cholera toxin in denuded oocytes and also that of follicle-stimulating hormone (FSH) in cumulus cell-enclosed oocytes. Cholera toxin or FSH alone each stimulated the synthesis of cAMP in oocyte-cumulus cell complexes, whereas pertussis toxin or AlF4- alone were without effect. Both cholera toxin and AlF4- augmented the stimulatory action of FSH on cAMP. These data suggest the involvement of guanyl nucleotides and G-proteins in the regulation of GVB, although different G-proteins and mediators may be involved at the oocyte and cumulus cell levels. Cholera toxin most likely acts by ADP ribosylation of the alpha subunit of Gs and increased generation of cAMP, whereas AlF4- appears to act by antagonizing a cAMP-dependent step.
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PMID:Modulation of meiotic arrest in mouse oocytes by guanyl nucleotides and modifiers of G-proteins. 132 Jun 58

To determine whether a nontoxic derivative of pertussis toxin obtained by recombinant DNA technology, PT-9K/129G, is a good candidate for a new pertussis vaccine, we examined the safety and the immunogenicity in children of a vaccine containing 15 micrograms of PT-9K/129G protein and 0.5 mg of aluminum hydroxide per dose. Fifty-three children 12 to 24 months of age and 21 infants aged 2 to 4 months were injected with two and three doses, respectively. The vaccine did not induce significant local or systemic reactions and elicited an increase of antibody titer in more than 98% of the children. The geometric mean of the toxin-neutralizing titers increased after each dose and was 85 units in children given two doses and 196 units in those given three doses. Two children who had detectable antibody levels before the first immunization had a high response (greater than 320 units) to the first vaccine dose. The findings suggest that PT-9K/129G is a promising antigen to be included in the development of acellular pertussis vaccines.
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PMID:Acellular pertussis vaccine composed of genetically inactivated pertussis toxin: safety and immunogenicity in 12- to 24- and 2- to 4-month-old children. 157 1

The occurrence of subcutaneous nodules at the injection site is one of the complications of diphtheria-tetanus-pertussis-poliomyelitis vaccination, but the causes and mechanisms involved are still poorly understood. An experimental study in the New Zealand rabbit enabled us to determine the frequency of occurrence of these nodules, how long they persist and the histopathologic features of the cells involved. Aluminium (Al) assays by electrothermal atomic absorption spectrometry allowed us to study concentrations both in nodules and the organism (serum, normal skin). The results show an absence of Al diffusion outside nodules, a correlation between infiltrate intensity and Al concentration in nodules and modifications in the histological constituents of nodule cells. The histological picture indicates a foreign body reaction to Al. All these data underscore the role of Al in the formation of early postvaccinal nodules at the injection site.
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PMID:Role of aluminium in skin reactions after diphtheria-tetanus-pertussis-poliomyelitis vaccination: an experimental study in rabbits. 158 78

Plasma membranes from bovine liver contain a phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PLC) activity that is activated by guanine nucleotides. The G-proteins involved retained their ability to activate bovine brain PLC-beta 1 in a guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)-dependent manner following extraction from the membranes with cholate and reconstitution with phospholipids. This reconstitution assay was used to purify the G-proteins by chromatography on heparin-Sepharose, DEAE-Sephacel, octyl-Sepharose, hydroxylapatite, Mono Q, and Sephacryl S-300 gel filtration. Gel electrophoresis showed that two alpha-subunits with molecular mass of 42 and 43 kDa were isolated to a high degree of purity, together with a beta-subunit. Neither alpha-subunit was a substrate for pertussis toxin-catalyzed ADP-ribosylation. Gel filtration of the final activity indicated an apparent molecular mass of 95 kDa, suggesting the presence of an alpha beta gamma heterotrimer. Immunological data revealed that the 42- and 43-kDa proteins were related to alpha-subunits of the Gq class recently purified from brain (Pang, I.-H., and Sternweis, P. C. (1990) J. Biol. Chem. 265, 18707-18712) and identified by molecular cloning (Strathmann, M., and Simon, M. I. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 9113-9117). The activation of PLC-beta 1 by the purified G-protein preparation was specific for nonhydrolyzable guanine nucleotides, the efficacy decreasing in order GTP gamma S greater than guanylimidodiphosphate greater than guanylyl(beta,gamma-methylene)-diphosphonate. Half-maximal activation required 4 microM GTP gamma S suggesting that the affinity of the G-proteins for GTP analogues is low. The GTP gamma S-dependent activation of PLC-beta 1 required millimolar Mg2+ and was inhibited by guanosine 5'-O-(2-thiodiphosphate) and by excess beta gamma-subunits. Aluminum fluoride also activated PLC-beta 1 in the presence of the G-proteins. The G-proteins were inactive toward PLC-gamma 1 or PLC-delta 1. In summary, these findings identify two G-protein activators of PLC-beta 1 that have the properties of heterotrimeric G-proteins and are members of the Gq class.
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PMID:Purification and characterization of two G-proteins that activate the beta 1 isozyme of phosphoinositide-specific phospholipase C. Identification as members of the Gq class. 165 41

Specific binding of the Ca++ antagonist desmethoxyverapamil, (-)-[3H]D888, to cell membranes of equine portal vein smooth muscle was inhibited in a concentration-dependent manner by guanosine 5'-O-(gamma-thio)triphosphate and ATP but was little affected by guanosine 5'-O-(beta-thio)diphosphate, noradrenaline or phorbol 12-myristate 13-acetate ester. Inhibition constants for GTP and ATP were in the range of 0.1 to 0.3 mM. From Scatchard plots and dissociation kinetic experiments, it is proposed that D888 high affinity binding sites are transferred into low affinity sites. In intact strips of rat portal vein bathed in physiological solution, both noradrenalin and a combination of aluminum chloride and sodium fluoride inhibited (-)-[3H]D888 binding, whereas guanosine 5'-O-(gamma-thio)triphosphate was without effect. In strips pretreated with 1 microM prazosin or 10 micrograms/ml pertussis toxin (PTX) for 6 h, noradrenalin had no effect on specific (-)-[3H]D888 binding. In addition, inhibition of (-)-[3H]D888 binding in the presence of 3 microM noradrenalin was reversed in a concentration-dependent manner by prazosin but not by propranolol. Noradrenalin-induced contractions were inhibited in a concentration-dependent manner by D888. In strips preincubated with 10 micrograms/ml PTX for 6 h, the concentration-response curve was shifted to the left, indicating that removal of the PTX sensitive transduction pathway increased D888 affinity for its specific binding sites. These results show that (-)-[3H]D888 binding to Ca++ channels is changed by GTP analogs in a way that suggests that a PTX-sensitive guanine nucleotide-binding protein may directly interact with Ca++ channels in response to activation of alpha 1 adrenoceptors.
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PMID:Guanine nucleotide-binding proteins modulate desmethoxyverapamil binding to calcium channels in vascular smooth muscle. 165 17

Treatment of BC3H1 myocytes or 3T3-L1 fibroblasts with fluoroaluminate (AlF4-), a direct activator of G proteins, increased the tyrosine phosphorylation of a 42-kDa cytosolic protein. AlF4- induced a parallel increase in protein kinase activity toward myelin basic protein (MBP) in partially purified cell extracts. To test whether AlF4- was activating the 42-kDa MAP (mitogen-activated protein) kinase, extracts from AlF4--treated cells were taken through the chromatographic steps routinely used to purify MAP kinase from growth factor-stimulated cells. Following phenyl-Superose chromatography, a peak of MBP kinase activity eluted at a position characteristic of MAP kinase. Immunoblotting of the active fractions with anti-phosphotyrosine antibodies revealed a single reactive protein band of Mr 42,000. Stimulation of MAP kinase by AlF4- was rapid, peaking within 15 min and persisting for at least 1 h. In contrast, the activation of MAP kinase by insulin was transient, characteristic of its activation by growth factors in other cell types. Although concentrations of sodium fluoride greater than 1 mM also activated MAP kinase, this effect was shown to be dependent upon the simultaneous presence of aluminum ions in the medium. Activation of MAP kinase by AlF4- was not affected by either cellular depletion of protein kinase C or pretreatment of cells with pertussis toxin. Potential sites of action of AlF4- are discussed. These findings suggest that activation of a G protein(s) in intact cells can initiate events that result in tyrosine phosphorylation and activation of MAP kinase.
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PMID:Activation of mitogen-activated protein kinase in BC3H1 myocytes by fluoroaluminate. 170 25

Reactions to adsorbed diphtheria-pertussis-tetanus (DPT) vaccine have mostly been attributed to the pertussis organisms or pertussis components in the vaccine. Nevertheless reactions may also be due to other factors such as sensitization induced by aluminium adjuvants and impurities present in crude toxoids that cannot be removed by purification of toxoids after formalinization. Aluminium compounds such as aluminium phosphate and aluminium hydroxide are the most commonly used adjuvants with vaccines for human use. Due to the increasing concern about the toxicity of aluminium, other adjuvants like calcium phosphate may be evaluated as an alternative to aluminium adjuvants. To minimize reactions after immunization with DPT vaccine due to impurities in the toxoids, the use of toxoided purified toxins is suggested.
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PMID:Adverse reactions after injection of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or pertussis components in the vaccine. 175 87

Intraperitoneal injection of adsorbed diphtheria-purified pertussis-tetanus combined vaccine (DPPT) often causes an ascites-accumulating (A-A) reaction in guinea pigs. Those vaccines which caused A-A reaction increase the vascular permeability (VP) of the skin tissue at the intracutaneous injection sites. A total of 23 lots of DPPT were assayed for A-A and VP-increasing activities. A positive correlation between the volume of ascites accumulated and the intensity of VP was significant. Other kinds of aluminum-adsorbed (Al-Ad) vaccines such as Al-Ad tetanus and Al-Ad diphtheria-tetanus combined and Al-Ad hepatitis B vaccines induced little or no A-A reaction. These results were discussed from the viewpoint of quality control in the process of the production of DPPT.
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PMID:Accumulation of ascites and increase in skin vascular permeability observed by injection of adsorbed diphtheria-purified pertussis-tetanus combined vaccine in guinea pigs. 180 65

We recently reported that aluminum administration to beagles stimulates uncoupled bone formation in the marrow cavity which increases trabecular bone volume and generates new osseous networks within the axial skeleton. To investigate whether this osteogenic process results from direct stimulation of bone cell replication, we examined the mitogenic effects of aluminum on undifferentiated osteoblasts derived from the MC3T3-E1 clonal cell line. Addition of AlCl3 (1-50 microM) to serum-free culture medium of quiescent osteoblasts resulted in a dose-dependent increase in [3H]thymidine incorporation into DNA and a concordant increase in cell number to 48% of the density achieved at the maximum replicative rate induced by fetal bovine serum (FBS). The time course of aluminum-induced mitogenesis was similar to that of FBS, with onset of DNA synthesis detectable by 12 h and progressive increases in replicative rates observed over a 48-h study period. Moreover, maximal stimulation of DNA synthesis by AlCl3 and that by FBS were not additive, whereas aluminum exerted additional effects on cell replication when combined with low FBS concentrations. Analysis of cell cycle kinetics indicated that aluminum, analogous to FBS, influences the osteoblast replicative activity by inducing transition from the G0 to the S phase of the cell cycle. In addition, exposure of cells to aluminum resulted in rapid accumulation of c-fos mRNA by 30 min, indicating that aluminum, like fetal bovine serum, induced expression of growth-regulating genes. Deferoxamine mesylate, a chelator of aluminum, blocked the replicative actions of aluminum in a dose-dependent fashion. In contrast, pertussis toxin, a specific inhibitor of certain G-proteins, had no effect on the mitogenic effects of aluminum, indicating that aluminum-induced mitogenesis occurs by a pertussis toxin-insensitive pathway. Though the particular cellular pathway remains to be defined, these data provide initial evidence that aluminum-induced neoosteogenesis may depend upon direct stimulation of osteoblast replication.
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PMID:Aluminum-induced mitogenesis in MC3T3-E1 osteoblasts: potential mechanism underlying neoosteogenesis. 190


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