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

Recently new radioimmunoassay methods have been established to measure plasma concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), platelet release products which are set free when platelets aggregate. Plasma concentrations of beta-TG and PF4 were investigated in disorders with increased thromboembolic risk. Extremely high concentrations of these platelet proteins were found in patients with venous thrombosis, pulmonary embolism, polycythemia vera, and chronic renal failure. Moderately increased beta-TG and PF4 levels were observed in patients with peripheral vascular disease, coronary artery disease, chronic rheumatoid arthritis, multiple myeloma, and diabetes mellitus. These data indicate, that plasma concentrations of beta-TG and PF4 are useful parameters for the evaluation of the "in vivo" platelet activity. By using these new methods for clinical applications special blood sampling conditions have been taken into account; moreover one has to consider that the plasma levels of the platelet "release products" are dependent from renal function.
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PMID:[Clinical significance of the radioimmunological determination of beta-thromboglobulin and platelet factor 4]. 9 43

Ten hybridomas producing monoclonal antibodies (Mabs) against rabbit platelet factor 4 (PF4) were obtained from the fusion of splenocytes from mice immunized with purified rabbit PF4 and NSO mouse myeloma cells. When the reactivities of these monoclonal antibodies were determined by enzyme-linked immunosorbent assay and immunoblotting with human and rabbit PF4, they showed a high degree of specificity. Only one Mab recognized an epitope common to the human and rabbit molecules, the other nine reacted only with the rabbit protein. All the antibodies recognized, in crude platelet lysates, a band that comigrates with the purified PF4 protein. None of these antibodies cross-reacted with major rabbit or human platelet-poor plasma proteins. The significance of the Mabs in immunological and physiological studies is discussed.
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PMID:Production of novel monoclonal antibodies against rabbit platelet factor four. 173 41

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half-life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained--intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.
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PMID:Shortened platelet half-life in multiple myeloma. 373 Jun 14

Human basophils were stimulated to release histamine noncytotoxically by purified human platelet factor 4 (PF4) and the synthetic substituent peptide PF4(59-70). Histamine release was augmented significantly by 10(-7) M PF4 and 10(-5) M PF4(59-70), increased in a concentration-dependent manner, and attained a maximum at 3 X 10(-5) M PF4 and 3 X 10(-4) M PF4(59-70) similar to that achieved by goat anti-human myeloma IgE. PF4 (1-60) failed to initiate the release of histamine, which confirmed that the critical determinant of activity is in the carboxy-terminal sequence. Histamine release from basophils by optimally effective concentrations of PF4 and PF4(59-70) reached a plateau by 1-3 min, as contrasted with 10 min or longer for anti-IgE. The elimination of calcium and magnesium from the buffer suppressed the release of histamine by anti-IgE by 79-83%, but had no effect on that elicited by PF4(59-70). The rate of uptake of [125I]PF4 by purified basophils was similar on a molar basis to the rate of release of histamine by the same concentrations of PF4. The noncytotoxic release of histamine from human basophils by PF4 thus is temporally and biochemically distinct from that mediated by IgE and may be similar to that evoked by other polycationic stimuli.
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PMID:Stimulation of histamine release from human basophils by human platelet factor 4. 619 89

We have identified a circulating, heparin-like anticoagulant in a patient with multiple myeloma (IgG4 lambda) who had serious clinically evident bleeding that contributed to his death. Purification of the patient's circulating coagulation inhibitor was accomplished by ammonium sulfate concentration, anion exchange chromatography, and affinity chromatography on protamine sulfate. Analysis of the purified inhibitor showed that it was a proteoglycan that comigrated with heparan sulfate on lithium acetate-agarose-gel electrophoresis and that it contained 39 per cent L-iduronic acid. Control samples of heparan sulfate and heparin contained 29 and 68 per cent L-iduronic acid, respectively. Functional coagulation studies revealed that the purified inhibitor had cofactor activity with antithrombin III that could be abolished by prior incubation with protamine sulfate or platelet factor 4. Recognition of the existence of this or of other similar inhibitors in bleeding patients is important because of the potential for treatment with agents such as protamine sulfate and platelet factor 4, which neutralize the anticoagulant effects of proteoglycans.
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PMID:Circulating heparan sulfate anticoagulant in a patient with a fatal bleeding disorder. 623 89

The objective of this study was to characterize the heparin-binding properties of a protein secreted by mouse myeloma cells. The characterization was performed using clinical assays, such as heparin activity assays and heparin-induced thrombocytopenia (HIT) platelet activation assays. The tests were performed in the presence of heparin, low-molecular-weight heparins (LMWH), or heparinoids and either heparin-binding protein (HBP) or saline to determine whether the HBP affects the activity of heparins. The characterization of the HBP using heparin activity assays showed that the HBP shortened the prolonged clotting times of the activated partial thromboplastin time (aPTT) and thrombin clotting time induced by high concentrations of unfractionated heparin. The chromogenic assays for antithrombin (AT), thrombin inhibition, and factor Xa inhibition demonstrated that this effect is related to heparin concentrations below 0.5 IU/ml. The Heptest assay did not detect these differences. The HBP did not modify the anticoagulant effect of any LMWH or low- or high-sulfated glycosaminoglycans in the aPTT assay. Activation of donor platelets in the presence of unfractionated heparin, platelet factor 4 (PF4), and HIT-serum was not counteracted by the HBP in any of the assays. The characterization of the HBP using a PF4-enzyme-linked immunosorbent assay (ELISA) confirmed the lack of structural identity with PF4. However, the optical density data indicated that the protein structure may be similar to PF4 by binding to a PF4 antibody. These data suggest that the HBP isolated from mouse myeloma cells has a low affinity to heparin and interacts with the secondary binding site to AT and also perhaps to PF4.
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PMID:Effects of a heparin-binding protein on blood coagulation and platelet function. 1166 19

In this study, we have elucidated the chromosomal imbalances in the multistep pathogenesis and delineated several critical tumor suppressor gene (TSG) loci in multiple myeloma (MM). By using comparative genomic hybridization, allelotyping, and multicolor interphase fluorescence in situ hybridization, 5 MM cell lines and bone marrow CD138+ plasma cells from 88 Chinese patients with monoclonal gammopathy of undetermined significance (MGUS) and early and advanced stages of MM were investigated. In all MGUS and MM samples, chromosome copy number abnormalities were detected. A higher number of chromosomal imbalances and specific genetic alterations are involved in MGUS to MM transition (-6q, +3p, and +1p) and MM progression (+2p and +9q). In addition to -13q, we first found high frequencies (42% to 46%) of -4q involving high percentages (70% to 74%) of clonal plasma cells in both MGUS and MM, suggesting that inactivation of TSG in this region is also a potentially critical genetic event in MM tumorigenesis. By high-resolution allelotyping, we defined a common deletion region on 4q13.3 and found that a candidate TSG, platelet factor 4, was frequently silenced by promoter hypermethylation in MM (15 of 28) and MM cell lines (5 of 5). These data have opened up a new approach in the molecular targeting therapy and provide novel insights into MM tumorigenesis.
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PMID:4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4. 1707 31

This study was purposed to investigate the effects of viral vector-mediated gene transfer of platelet factor 4 (PF4) or 17-70 cDNA on cell growth of multiple myeloma (MM) in vivo. Full length and p17-70 cDNA of PF4 were cloned into virapower system to transfect packing cell line 293 and produce lentiviral vectors. 3 multiple myeloma cell lines were transferred platelet factor 4 or 17-70 cDNA by lentiviral vectors. SCID-rab mice models of multiple myeloma were established by injecting U266 multiple myeloma cells selected. The human light chain proteins and VEGF in serums of mice were detected every 2 weeks. The volumes and vascular density of tumors as well as survival time of mice were observed. The results showed that the MM cells expressing foreign genes were identified and screened. There were significant difference of VEGF levels in the supernatants of MM cells between each groups (p<0.01). The SCID-rab models of U266 cells were established successfully. There were significant differences in light chain protein and VEGF in serums among three groups (p<0.01). The light chain protein and VEGF in mice serums of 17-70 cDNA groups were less than that of PF4 group (p<0.01). The light chain protein and VEGF in mice serums of PF4 group were less than that of control group (p<0.01). There were significant differences in the tumor volumes and the vascular density of tumor among 3 groups (p<0.05). The results also showed that there were significant differences of overall survival in 3 different groups of SCID-rab MM models. The overall survival in control group was shortest as compared with other groups (p<0.05). It is concluded that the cell growth of multiple myeloma is suppressed in vivo by transfection of platelet factor 4 or 17-70 cDNA and the overall survival of transfected mice will be prolonged.
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PMID:[Suppression of multiple myeloma tumor growth in vivo by transfection of platelet factor 4 or 17-70 cDNA]. 2112 55