Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human peripheral blood eosinophils adhered specifically to microtitre plates coated with plasma fibronectin (Fn) in a dose- and time-dependent fashion. Adhesion was optimal at 60 min at a concentration of 100 micrograms/ml. Adherence to Fn was up-regulated by platelet-activating factor (PAF; optimum concentration of 10(-6) M) and was significantly inhibited by a polyclonal anti-Fn antibody (P < 0.05). The following evidence suggested that eosinophil adhesion to Fn was mediated by alpha 4 beta 1: (1) eosinophil adherence to Fn was not inhibited by an Arg-Gly-Asp-Ser (RGDS) synthetic peptide; (2) there was a dose-dependent adherence of eosinophils to microtitre plates coated with the 40,000 MW proteolytic fragment of Fn that contains the CS-1 alpha 4 beta 1 binding region, whereas adherence to the 120,000 MW chymotryptic fragment of Fn, which contains the RGD-dependent binding site, was weak and only observed at high concentrations (> 250 micrograms/ml); (3) significant inhibition of eosinophil adherence to Fn was achieved by monoclonal antibodies (mAb) against the alpha chain of VLA-4 but not by a mAb against CD45 or a mouse myeloma antibody as negative controls. After adhesion to Fn, eosinophils were investigated for their capacity to release leukotriene C4 in response to stimulation with a suboptimal concentration of calcium ionophore (2 x 10(-6) M). Significant enhancement of release was detected with Fn-coated plates but not with the control bovine serum albumin (BSA) (P < 0.01). Furthermore, this enhancement was significantly inhibited by the alpha 4 beta 1 mAb HP2/1 (P < 0.05) but not by an anti-CD45 mAb. From these studies we conclude that (1) alpha 4 beta 1 (VLA-4) integrin is a major receptor for Fn on human eosinophils and (2) adhesion to Fn may prime eosinophils for mediator release during allergic inflammation.
 ...
PMID:Adhesion to fibronectin primes eosinophils via alpha 4 beta 1 (VLA-4). 792 93

We report here the case of a patient with the Shy-Drager syndrome and multiple myeloma who had evidence consistent with a central neural autoimmune basis for sympathetic autonomic failure. Autonomic function testing showed no recordable peroneal skeletal muscle sympathoneural traffic, normal arterial norepinephrine (NE) spillover during supine rest and no increment in NE spillover during exposure to lower body negative pressure. The patient's cerebrospinal fluid and serum contained an immunoglobulin G that bound to rat locus ceruleus (LC) in an in vitro test system. The myeloma protein was of the lambda subtype and bound in the rat LC, without binding in the substantia nigra, as demonstrated with anti-lambda antiserum. Since in this case the monoclonal antibody produced by the myeloma bound specifically to LC cells, the results are consistent with the hypothesis that in this patient the Shy-Drager syndrome may have had an immune-mediated basis.
 ...
PMID:Autoimmune autonomic failure in a patient with myeloma-associated Shy-Drager syndrome. 892 51

In this study we have investigated the presence of PAF receptor (PAF-R) on 5 myeloma cell lines (U266, L363, IM9, OPM2 and XG1), their metabolism of PAF and lyso PAF, and the effect of PAF on their growth. All myeloma cell lines express a PAF acetylhydrolase activity and metabolize [3H]PAF and [3H]lyso PAF in 1-alkyl-2-acyl analogue of phosphatidylcholine. Polymerase chain reaction on reverse transcript (RT-PCR) experiments indicate that OPM2, U266, IM9, XG1 and L363 cells express the PAF-R transcript 1 but not the PAF-R transcript 2. Flow cytometry experiments reveal that PAF-R are present on these myeloma cell lines. PAF and the non-metabolizable PAF agonist 1-O-hexadecyl-2-N-methycarbamyl-glycero-3-phosphocholine have no effect on the growth of OPM2, U266, IM9, XG1 and L363 assessed by [3H]thymidine incorporation into DNA. As a positive control of PAF effect on myeloma cells, PAF (1 microM) enhances by 100% the immunoglobulin synthesis by IM9 cells cultured for 48 h. In conclusion the five myeloma cell lines used in this study metabolize PAF through the deacetylation/reacylation pathway. They express membrane PAF-R through the PAF-R mRNA transcript 1 but PAF does not affect their growth.
 ...
PMID:Metabolism and effect of platelet-activating factor on the growth of human myeloma cell lines. 1073 2

Streptococcus pneumoniae is a major human pathogen and many interactions of this bacterium with its host appear to be mediated, directly or indirectly, by components of the bacterial cell wall, specifically by the phosphorylcholine residues which serve as anchors for surface-located choline-binding proteins and are also recognized by components of the host response, such as the human C-reactive protein, a class of myeloma proteins and PAF receptors. In the present study, we describe the identification of the pneumococcal pce gene encoding for a teichoic acid phosphorylcholine esterase (Pce), an enzymatic activity capable of removing phosphorylcholine residues from the cell wall teichoic acid and lipoteichoic acid. Pce carries an N-terminal signal sequence, contains a C-terminal choline-binding domain with 10 homologous repeating units similar to those found in other pneumococcal surface proteins, and the catalytic (phosphorylcholine esterase) activity is localized on the N-terminal part of the protein. The mature protein was overexpressed in Escherichia coli and purified in a one-step procedure by choline-affinity chromatography and the enzymatic activity was followed using the chromophoric p-nitrophenyl-phosphorylcholine as a model substrate. The product of the enzymatic digestion of 3H-choline-labelled cell walls was shown to be phosphorylcholine. Inactivation of the pce gene in S. pneumoniae strains by insertion-duplication mutagenesis caused a unique change in colony morphology and a striking increase in virulence in the intraperitoneal mouse model. Pce may be a regulatory element involved with the interaction of S. pneumoniae with its human host.
 ...
PMID:Identification of the teichoic acid phosphorylcholine esterase in Streptococcus pneumoniae. 1126 Apr 77