Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesenteric and bronchial lymph node cells from sheep immunized with Ascaris suum antigens in combination with Bordetella pertussis vaccine were fused with mouse myeloma cell lines, P3-X63-Ag8.653, NSO.U and NS1.1.Ag1.1. One heterohybridoma cell line (NS1.1.Ag1.1 x sheep) producing ovine immunoglobulin E was detected by the passive cutaneous anaphylaxis test.
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PMID:Obtention of ovine IgE from heterohybridoma. 788 39

Lysophosphatidic acid (LPA) induces mitogenic responses in cultured fibroblasts through a pertussis toxin-sensitive signaling pathway. In contrast, we have shown that LPA inhibits the proliferation of Sp2/0-Ag14 myeloma cells. To resolve this apparent controversy, LPA-elicited responses in cell proliferation and the underlying second messenger mechanisms were compared in Sp2/0-Ag14 myeloma and NIH 3T3 fibroblast cells. The antimitogenic response was not elicited by micromolar concentrations of phosphatidic acid, phosphatidylglycerol, or diacylglycerol. In NIH 3T3 and Sp2 cells, LPA elicited an increase in inositol trisphosphate and a subsequent transient increase in free cytoplasmic Ca2+. Unlike the mitogenic response in NIH 3T3 cells, the antimitogenic effect was not affected by pertussis toxin; on the contrary, it was accompanied by an increase in cAMP. In Sp2 cells, cAMP analogs, forskolin, and isobutylmethylxanthine inhibited cell proliferation and enhanced LPA action in an additive manner, suggesting that an LPA-elicited increase in cAMP-mediated signaling was responsible for the antimitogenic response. In addition to the mitogenic response in fibroblasts and the antimitogenic response in tumor cell lines, there are some cell types (Jurkat T-cell lymphoma and primary astrocytes) in which LPA is ineffective in altering cell proliferation. The cell-type-specific dual action of LPA suggests that this endogenous lipid mediator when released from activated cells might play an important role as a regulator, rather than a ubiquitous inducer, of cell proliferation.
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PMID:Lysophosphatidic acid possesses dual action in cell proliferation. 812 4

Peptides which stimulate the formation of inositol phosphates (InoPs) in lymphocyte cell lines were identified by screening synthetic peptide libraries composed of random sequences of hexapeptides. The peptides containing the consensus sequence XKYX(P/V)M were found to be most active in the phospholipase C (PLC)-mediated formation of InoPs in a human B myeloma cell line, U266. The peptides also stimulated the phosphoinositide hydrolysis and the release of [Ca2+]i in HL60 and U937 cell lines. On the other hand, these peptides showed no effect in the following cell lines: NIH3T3, PC12, Daudi, Sp2, Jurkat, H9, Molt-4, SupT-1, K562, and RBL-2H3. The result suggests the possibility that the peptides may have cell type specificity. Experiments with one of the active peptides, WKYMVM-NH2 showed that its action mimics the effect of AlF4- which is a G-protein activator in the InoPs generation, and pertussis toxin partially blocked the InoPs accumulation and [Ca2+]i release induced by the peptide in the U266 cells. Binding assays with the peptide labeled with 125I showed that U266 cells have a saturable number of binding sites for the peptide. Taken together, these results suggest that the peptides could activate PLC-mediated signal transduction via a pertussis toxin-sensitive G-protein coupled receptor in certain cell types.
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PMID:Identification of the peptides that stimulate the phosphoinositide hydrolysis in lymphocyte cell lines from peptide libraries. 862 7

Mouse monoclonal antibodies MAHI 4 and MAHI 10 reactive with Haemophilus influenzae lipopolysaccharide (LPS), were generated by fusing mouse myeloma cells with spleen cells of mice immunized with H. influenzae strain RM.7004-XP-1. The antibody MAHI 4 reacted in whole-cell enzyme immunoassay (EIA) and colony-dot-immunoblotting with 20 of 123 H. influenzae strains and to a few other human Haemophilus spp. and Neisseria spp., but not to any Bordetella pertussis, B. parapertussis, Aeromonas spp. or Moraxella catarrhalis strains tested. This suggests a specific epitope accessible to recognition in just a few strains. This conclusion was supported by the data on binding of MAHI 4 to only three of 18 H. influenzae LPSs tested, but not to any Haemophilus ducreyi or enterobacterial LPSs. The antibody MAHI 10 bound to 80 of 123 strains of H. influenzae and to a few strains of Neisseria spp. and M. catarrhalis as evaluated by EIA and colony-dot-immunoblotting, which suggests an epitope accessible to recognition in 65% of the H. influenzae strains tested. The antibody MAHI 10 reacted with 10 of 18 H. influenzae LPSs as determined by EIA. By using polysaccharides, obtained after both mild acidic hydrolysis, strong alkali treatment, and dephosphorylation, as inhibitors of the antibodies binding to H. influenzae LPS antigens it was shown that phosphate groups were essential for the binding of MAHI 10 to LPS but they did not affect antigenic recognition by MAHI 4. None of the monoclonal antibodies bound to isolated lipid A, but the aggregation caused by the fatty acids of lipid A was essential for optimum epitope recognition. Enzymatic treatment of homologous LPSs with galactose-oxidase led to products which were between 20 to 30 times less effective as inhibitors of the binding of the MAHI 4 than the native LPSs. Taken together the results indicate that MAHI 4 has the following pentasaccharide as the epitope Gal beta 1-->2 Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1--> Kdo(P). These results emphasize the importance of the terminal beta-Gal residue in the definition of the MAHI 4 specificity, and of the terminal phosphorylated saccharide residues of some of the Haemophilus LPSs for the MAHI 10 specificity.
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PMID:Monoclonal antibodies against Haemophilus influenzae lipopolysaccharides: clone MAHI 4 binding to a pentasaccharide containing terminal beta-Gal residues and clone MAHI 10 recognizing terminal phosphorylated saccharide residues. 893 39

The chemokine stromal cell-derived factor-1alpha (SDF-1alpha) and its G-protein-linked receptor CXCR4 are involved in hematopoietic progenitor cell and lymphocyte migration. The integrin VLA-4 is a cell adhesion receptor for CS-1/fibronectin and VCAM-1 and constitutes one of the main adhesion receptors mediating myeloma cell adhesion to bone marrow (BM) stroma in multiple myeloma (MM). It is shown here that MM CD38(hi)CD45RA(-) BM cells and myeloma-derived cell lines expressed CXCR4 and displayed a moderate chemotactic response to SDF-1alpha. Because cell migration in response to SDF-1alpha might require a dynamic regulation of integrin function, it was investigated whether SDF-1alpha can modulate VLA-4 function on myeloma cells. SDF-1alpha rapidly and transiently up-regulated VLA-4-mediated myeloma cell adhesion to both CS-1/fibronectin and VCAM-1, which was inhibited by pertussis toxin and cytochalasin D, indicating the involvement of G(i) protein downstream signaling and an intact cytoskeleton. Modulation of VLA-4-dependent myeloma cell adhesion by SDF-1alpha could contribute to the trafficking and localization of these cells in the BM microenvironment.
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PMID:Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. 1115 7

Bordetella pertussis is a fastidious aerobic, Gram-negative coccobacillus that causes the classical disease of whooping cough. We present a 63 years old man with multiple myeloma who was admitted to the medical department with cough, hoarseness and fever. Bronchopneumonia was suspected and two courses of beta-lactam antibiotics had beneficial effect on his clinical condition, but his respiratory symptoms persisted. Eventually, B. pertussis grew in an aerobic blood culture. Delayed treatment with clarithromycin had little or no effect on his cough. To our knowledge this is the third reported case of B. pertussis bacteraemia. All three patients have been immunocompromized. Growth in blood culture may be slow, and prolonged incubation (at least 6 days) of the blood culture bottles and subculture to a special culture medium is necessary for isolation of B. pertussis.
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PMID:Isolation of Bordetella pertussis in blood culture from a patient with multiple myeloma. 1593 87

Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid which is known to induce diverse cellular responses through at least five G-protein-coupled receptors on various cell types. However, neither the distribution of S1P receptors nor the effects of S1P on multiple myeloma (MM) cells are fully understood. Here, we show that MM cells express the S1P receptors, S1P1, S1P2, and S1P3. Furthermore, S1P protects MM cells against Dex-induced apoptosis. Importantly, S1P upregulates Mcl-1 expression in a time- and concentration-dependent manner in human MM cell lines. Treatment of MM cells with pertussis toxin (PTX), a pan-S1P receptor inhibitor, results in blockage of S1P-induced upregulation of Mcl-1. These data demonstrate that S1P upregulates the expression of Mcl-1 and protects MM cells from Dex-induced apoptosis, providing the preclinical framework for novel therapeutics targeting at both Mcl-1 and/or S1P to improve the patient outcome in MM.
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PMID:Sphingosine 1-phosphate induces Mcl-1 upregulation and protects multiple myeloma cells against apoptosis. 1842 79

Prokineticin-1 (PK1) has been identified as a mitogen-specific protein for the endothelium of steroidogenic glands. Here we report a novel function of PK1 in the regulation of multiple myeloma (MM) cells. PK1 activates multiple signals including mitogen-activated protein kinase (MAPK), PI3K-AKT, and Jak-STAT3, sphingosine kinase-1 (SPK1) in MM cells. Treatment of MM cells with PK1 causes a time- and dose-dependent phosphorylation of MAPK, AKT and STAT3 and upregulation of SPK1 expression and cellular activity. We also show that PK1 upregulates Mcl-1 expression in a time- and dose-dependent manner in human MM cell lines and in the cells of patients with MM. Pertussis toxin, a pan-PK1 receptor inhibitor, can block PK1-induced upregulation of Mcl-1, indicating it relates to a G-protein-coupled receptor. We also show that PK1 protects MM cells against apoptosis induced by starvation for fetal calf serum (FBS), or for FBS and IL-6. Taken together, PK1 activates multiple signaling pathways and, upregulates Mcl-1 expression, leading to proliferation and survival of MM cells.
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PMID:Prokineticin-1/endocrine gland-derived vascular endothelial growth factor is a survival factor for human multiple myeloma cells. 2079 91

Guidelines recommend vaccination starting 12 months after autologous hematopoietic stem cell transplant (aHCT), but there is varying practice for patients on maintenance therapy, with some centers not immunizing at all. Because of decreased vaccine rates among the general population causing loss of herd immunity, we aimed to establish the safety and efficacy of revaccinating multiple myeloma patients on lenalidomide maintenance (LM). Of the 122 patients who were vaccinated after aHCT between 2010 and 2014 at Memorial Sloan Kettering Cancer Center, 91 (75%) were on LM. Vaccine responses were defined by increases between pre- and postvaccination titers. Reponses varied by vaccine type with 76% responding to pertussis, 70% diphtheria, 60% tetanus, 71% Haemophilus influenzae, and 58% pneumococcal. All patients retained minimal levels of polio immunity, but 27% responded with increased titers. Fewer patients received hepatitis A and B, but of those who did, 30% responded to hepatitis A and 40% to hepatitis B. No differences were seen in rates of response for those on LM at time of vaccination compared with those who were not. There were no vaccine-related adverse effects. Reimmunization with inactivated vaccines in patients on LM is therefore both safe and effective, offering this population immunity to vaccine-preventable diseases.
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PMID:Revaccination after Autologous Hematopoietic Stem Cell Transplantation Is Safe and Effective in Patients with Multiple Myeloma Receiving Lenalidomide Maintenance. 2928 18

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.
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PMID:Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study. 2984 44


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