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)

Protein tyrosine phosphorylation in human neutrophils was examined by immunoblotting with antibodies specific for phosphotyrosine. The addition of the human hormone granulocyte-macrophage colony stimulating factor to human neutrophils caused an increase in the tyrosine phosphorylation levels of several proteins. The increases in at least two of these proteins having molecular masses of 40 kDa (p40) and 54 kDa (p54) were rapid and were inhibited in pertussis toxin treated cells. The newly synthesized tyrosine kinase inhibitor ST 638 inhibited the increases in the levels of the tyrosine phosphorylation in p92, p78, p54 and p40 proteins. The epidermal growth factor receptor tyrosine kinase inhibitors were less effective. The addition of the chemotactic factor fMet-Leu-Phe to human neutrophils also caused an increase in tyrosine phosphorylation in some of these proteins. The pattern of the fMet-Leu-Phe-induced tyrosine phosphorylation was different from that produced by GM-CSF. The increases were also inhibited by ST 638. In addition, ST 638 inhibited superoxide production but not actin polymerization in control and GM-CSF-treated cells stimulated with fMet-Leu-Phe. Moreover, the active but not inactive phorbol esters increase the tyrosine phosphorylation only in the 40 kDa protein. These results suggest several points: (a) some of the responses produced by GM-CSF and fMet-Leu-Phe are mediated through tyrosine phosphorylation, (b) the GM-CSF receptor is coupled to a pertussis toxin sensitive G-protein, (c) the 40 kDa protein is probably the Gi alpha 2, and (d) the 78 or the 92 kDa protein is most likely the receptor for GM-CSF, which indicates that the receptor may have a tyrosine kinase domain.
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PMID:Tyrosine phosphorylation in human neutrophil. 247 9

Granulocyte-macrophage colony-stimulating factor, GM-CSF, potentiates superoxide generation produced by human neutrophils stimulated with fMet-Leu-Phe and platelet-activating factor, PAF, but not by phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan. The potentiation is greatest in fMet-Leu-Phe-stimulated cells. This indicates that the actions of only certain receptors are potentiated by GM-CSF. Incubation of the cells with the protein kinase inhibitor H-7 or with the protein synthesis inhibitor cyclohexamide before the addition of GM-CSF does not affect the observed potentiation. The rationales behind these studies are to examine the roles of protein kinase C and protein synthesis in the action of GM-CSF. The data suggest that neither protein kinase C nor protein synthesis is necessary for GM-CSF action. On the other hand, no potentiation can be seen in the presence of cytochalasin B. Unlike intact cells, GM-CSF does not enhance superoxide production by cytoplasts stimulated with fMet-Leu-Phe. The rationale behind the use of cytoplasts is to examine the role of granules and/or nucleus in GM-CSF action, and the data indicate that one or more of these two components is necessary for the priming effect of GM-CSF. The amount of actin associated with the cytoskeleton under control of fMet-Leu-Phe-stimulated condition is the same in normal and GM-CSF-treated human neutrophils. Botulinum D toxin ADP-ribosylates a protein with a molecular weight of 22 kDa. This ribosylation is reduced in homogenates obtained from cells pretreated with botulinum D toxin or GM-CSF. Botulinum D toxin does not affect the basal or the fMet-Leu-Phe-induced rise in the intracellular concentration of free calcium in human neutrophils. GM-CSF also increases the rise in intracellular concentration of free calcium in human neutrophils stimulated with PAF or fMet-Leu-Phe. The increases are inhibited by pertussis toxin. Several important conclusion can be drawn from these data. 1) GM-CSF potentiates the rise in Ca2+i produced by PAF and fMet-Leu-Phe, and these potentiations are inhibited in pertussis-toxin-treated cells. 2) GM-CSF does not prime cytoplasts to stimulation by fMet-Leu-Phe. This suggests that the granules and/or nucleus are necessary for the priming action. 3) The priming by GM-CSF is not mediated by the H-7-sensitive protein kinase C, botulinum D-sensitive G-protein, or protein synthesis.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor on superoxide production in cytoplasts and intact human neutrophils: role of protein kinase and G-proteins. 254 9

Both TNF and and granulocyte/macrophage CSF (GM-CSF) can activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil degranulation. The secretion of lactoferrin of secondary granules and myeloperoxidase (MPO) of primary granules from single adherent human neutrophils was assayed by use of a reverse hemolytic plaque assay. Both rTNF and rGM-CSF caused secretion of lactoferrin in a dose-dependent manner. Both agents also caused secretion of MPO, but only in the presence of cytochalasin B. Preincubation with pertussis toxin inhibited rGM-CSF-induced secretion of both lactoferrin and MPO. rTNF-induced MPO secretion was also blocked by pertussis toxin, whereas lactoferrin secretion was only slightly affected. Neither rTNF nor rGM-CSF caused any detectable changes in the concentration of cytoplasmic free Ca2+ in fura-2-loaded cells. However, when neutrophils were loaded with increasing concentrations of quin-2 to buffer any local, not detectable, changes in the concentration of cytoplasmic Ca2+, both rTNF- and rGM-CSF-induced secretion of lactoferrin and MPO were almost totally abolished at a relatively low quin-2 concentration. These results suggest a role of a regulatory G-protein and minute local changes in the concentration of cytoplasmic Ca2+ in TNF- and GM-CSF-induced neutrophil degranulation.
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PMID:Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrophil degranulation. 265 22

Guillain-Barre syndrome is known as one of the autoimmune disease, but the etiology, pathophysiology relating immune reaction, as well as the treatment are not established. It still causes physical handicap although its rate is low. The causes, clinical symptoms and outcome of 132 cases of Guillain-Barre syndrome have been analyzed. The patients' ages ranged from 4 months to 15 years. The antecedent events for 56.1% of the patients were known. These were upper respiratory tract infection, unexplained fever, vomiting, diarrhea, vaccination, measles, german measles, shigellosis, mumps, hepatitis, pertussis and surgery in order of frequency. The CSF protein level reached a maximum at 12.3 +/- 9.5 days. Steroids did not influence the outcome of this disease. More studies are necessary to conquer the disease.
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PMID:Guillain-Barre syndrome in Korean children. 274 76

Colony-stimulating factor 1 (CSF-1) regulates the survival, growth, and differentiation of monocytes through binding to a single class of high affinity receptors. The present studies demonstrate that the interaction of CSF-1 with monocyte membranes is associated with a 2.4-fold increase in specific binding of the GTP analogue, GTP gamma S. Scatchard analysis of the GTP gamma S binding data indicated that CSF-1 stimulates GTP binding by increasing the affinity, rather than the number, of available sites. This stimulation of GTP binding by CSF-1 was also associated with an increase in GTPase activity. Furthermore, the CSF-1-induced stimulation of GTPase activity was sensitive to pertussis toxin. We also demonstrate that CSF-1 stimulates Na+ influx into monocytes by an amiloride-sensitive mechanism, presumably the Na+/H+ antiport. This CSF-1-stimulated influx of Na+ was further associated with an increase in Na+,K+-ATPase activity. Moreover, this stimulation of Na+ influx and Na+,K+-ATPase activity by CSF-1 was sensitive to pertussis toxin. Finally, we demonstrate that CSF-1-induced proliferation is also a pertussis toxin-sensitive event. The present findings thus suggest: 1) that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein; and 2) that a pertussis toxin-sensitive G protein is involved in the induction of Na+ influx by CSF-1.
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PMID:Colony-stimulating factor 1-induced Na+ influx into human monocytes involves activation of a pertussis toxin-sensitive GTP-binding protein. 284 56

The effect of human tumor necrosis factor (TNF) on early-passage HL-60 cells was studied. A transient phase of increased [3H]thymidine (TdR) incorporation was noted at 20-24 hr of exposure to TNF. This increase was disproportionate to the much slighter stimulation of the percentage of S-phase cells, which was measured by flow cytometry. Evidence for increased metabolic trapping of [3H]TdR following TNF treatment was apparent from whole cell uptake experiments. The salvage pathway enzyme TdR kinase was therefore measured and was found to be elevated comparably to [3H]TdR uptake. The mechanism of TNF regulation of TdR kinase was further investigated by a series of combination treatment experiments using other biologic factors and pharmacologic inhibitors of various intracellular steps. The response to TNF was not potentiated or reproduced by IL-1, IL-2, IL-3, IL-4, G-CSF, M-CSF, GM-CSF or alpha- or gamma-interferon. Blockers of early signal transduction steps, including H7, W7, sphingosine, and pertussis toxin, failed to inhibit TNF stimulation of [3H]TdR incorporation. mRNA synthesis inhibition with alpha-amanitin blocked this TNF effect, as did cAMP but not cGMP analogues. A sensitizing effect was noted with amiloride or cytochalasin B, characterized by greater relative increases of [3H]TdR incorporation and TdR kinase activity in response to TNF. In the presence of cytochalasin B, TNF treatment resulted in no change or slight decreases in the percentage of S-phase cells. Regulation of TdR kinase could thereby be dissociated from the usual cell cycle control. This study thus documents a unique example of stimulation of thymidine salvage pathway metabolism by a biologic factor, dissociable from overall cell cycle regulation.
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PMID:Stimulation by tumor necrosis factor of HL-60 thymidine salvage pathway metabolism dissociated from proliferation. 316 95

A 1 year old Caucasian male born with an omphalocoele, malrotation of the large bowel, and Ladd's bands developed an E. coli wound infection and subsequent meningitis-ventriculitis which responded to antibiotic therapy. Aqueductal stenosis and obstructive hydrocephalus initially was treated with a ventriculoperitoneal shunt. After a routine diphtheria-pertussis-tetanus immunization, the child developed a CSF ascites which resolved following a ventriculoatrial shunt.
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PMID:Cerebrospinal fluid ascites: a complication of a ventriculoperitoneal shunt. 504 7

A new semisynthetic 1-oxa-beta-lactam derivative, 6059-S, was evaluated for its safety and efficacy in children. Twenty-five patients were treated with 10 to 274 mg/kg per day of 6059-S by intravenous administrations. The diagnosis of the patients were acute pharyngitis (2), acute bronchitis (2), pneumonia (4), pertussis (4), acute enterocolitis (2), recurrent urinary tract infection (2), suspected septicemia (3), and acute purulent meningitis (1); and the remaining 5 patients were considered to have nonbacterial infections. The pathogens recovered were Streptococcus pneumoniae (1), Haemophilus influenzae (4), Haemophilus parainfluenzae (1), Enterobacter cloacae (1), Enterobacter aerogenes (1), Proteus morganii (1), Psuedomonas aeruginosa (2) and Salmonella typhimurium (1). All the patients of bacterial infections were cured after the 6059-S therapy. However, Pseudomonas aeruginosa and Salmonella typhimurium were not eradicated after the 6059-S therapy, and the rate of bacterial disappearance was 75%. Diarrhea (3), precordial pain (2, only in cases with high-dose therapy), transient elevation of GOT and GPT (2), and transient eosinophilia (2) were found to be associated with the 6059-S therapy. However, no severe adverse reactions were encountered. Half life of the serum 6059-S level was 1.34 +/- 0.16 hours. CSF concentrations in a case with Haemophilus influenzae meningitis ranged 4.0 to 9.7 mcg/ml after an intravenous injection of 34.3 to 75 mg/kg of 6059-S. From the present study, 6059-S appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections. It remains to be further determined whether 6059-S is superior to ABPC in the treatment of Haemophilus influenzae meningitis.
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PMID:[Clinical evaluation of 6059-S therapy in children (author's transl)]. 645 68

Cefoxitin (CFX) was evaluated for its safety and efficacy in children. Fifteen patients were treated with 73-125 mg/kg per day of CFX by intravenous administrations. The diagnosis of the patients were acute pharyngitis (4), pneumonia (2), pertussis and pneumonia (1), urinary tract infection (3); and the remaining 5 patients were esteemed to have nonbacterial infections. All the 10 patients of bacterial infections were cured after the CFX therapy. The pathogens recovered were Streptococcus pyogenes (1), Streptococcus pneumoniae (3), Haemophilus influenzae (2), Escherichia coli (2), enteropathogenic Escherichia coli (1), and Klebsiella pneumoniae (1). All the strains isolated were susceptible to CFX, but the 2 isolates of Haemophilus influenzae had relatively high MIC values (12.5 mcg/ml). Diarrhea (3 cases) and transient neutropenia (1 case) were found to be associated with the CFX therapy. However, no severe adverse reactions were encountered. Half-life of the serum level was short (24.1 minutes) and excretion into the urine was rapid. CSF concentration obtained 30 minutes after an intravenous injection of 50 mg/kg of CFX in 1 case with inflamed meninges was considerably high (8.3 mcg/ml). CFX appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections.
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PMID:[Clinical evaluation of cefoxitin in children (author's transl)]. 728 18

The tyrosine phosphorylation responses initiated in human neutrophils by soluble and particulate agonists were characterized. Chemotactic factors, hematopoietic growth factors, and inflammatory microcrystals stimulated in a time- and concentration-dependent manner the tyrosine phosphorylation of distinct patterns of substrates: pp120, pp85, pp70, and pp60 in the case of chemotactic factors; pp155, pp130, pp120, pp85, pp60, and pp40 in the case of granulocyte macrophage-CSF; and pp130, pp120, pp70, and pp60 in the case of monosodium urate (MSU) crystals. Several of the single bands on one-dimensional blots (including pp40, pp70, and pp120) could be resolved into multiple spots on two-dimensional gels. The responses of several other chemotactic factors resembled those of FMLP. Cytokineplasts retained the capacity to respond to FMLP, granulocyte-macrophage-CSF, or MSU crystals with a stimulation of tyrosine phosphorylation, and contained the major substrates detected in intact neutrophils. Several unrelated tyrosine kinase inhibitors (herbimycin A, genistein, and erbstatin) strongly diminished the tyrosine phosphorylation response to chemotactic factors. Pertussis toxin abrogated the tyrosine phosphorylation response to FMLP, whereas protein kinase C (Ro 21-8220, chelerithryn) inhibitors were without effect. Chelation of intracellular calcium attenuated the tyrosine phosphorylation response to FMLP. These results indicate that G proteins play a crucial role in the coupling of chemotactic factor receptors to tyrosine phosphorylation and that this coupling occurs in parallel to that of phospholipase C. These results also underline the complexity of the transduction pathways implicated in the initiation of tyrosine phosphorylation.
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PMID:Tyrosine phosphorylation in activated human neutrophils. Comparison of the effects of different classes of agonists and identification of the signaling pathways involved. 751 26


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