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)

The oxidation of the ribose ring of cytidine-5'-diphospho-choline (CDPC) by periodate to produce reactive dialdehydes was used to couple this activated reagent onto various proteins, onto Ficoll 400 and onto Sepharose 4B. Careful control of parameters of the different steps of the reaction enabled us to synthesize conjugates with a graded number of nucleotide residues. Human serum albumin conjugates with a relatively high degree of substitution were used to demonstrate and to measure anti-phosphorylcholine antibodies and the acute phase reactant, C-reactive protein by precipitation or passive haemagglutination techniques. These methods for measuring C-reactive protein in serum of patient suffering from acute inflammation may be useful for clinicians. CDPC-AH Sepharose was used to purify the phosphorylcholine-binding myeloma protein HOPC8 and to separate C-reactive protein from the bulk of serum proteins. Improvements of this technique will certainly lead to the complete purification of C-reactive protein.
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PMID:Cytidine-5'-diphospho-choline conjugates. I.--Synthesis and fixation to phosphorylcholine-binding proteins. 49

Culture filtrate extracts from a number of dermatophyte and Aspergillus species precipitate with human C-reactive protein (CRP) and the lectin Con A. Using immobilized Con A, a peptidopolysaccharide (PPS) has been isolated from Epidermophyton floccosum culture filtrate by affinity chromatography and shown to precipitate with Con A, human CRP sera and a mouse myeloma serum with specificity for phosphorylcholine (PC). The PPS contains carbohydrate (60%), protein (35%), choline and phosphate. The carbohydrate portion consists almost entirely of D-mannose with only 2% hexosamine. Amino acid analysis revealed that serine, threonine, proline and glycine accounted for over 50% of the total amino acids present. Precipitation of E. floccosum PPS and pneumococcal C substance with human CRP sera and mouse anti-PC serum were compared in quantitative precipitin studies. Inhibition studies demonstrated that PC is a potent inhibitor of the serum CRP-PPS and myeloma protein-PPS precipitation reactions. The involvement of 'C substances' in a variety of biological processes is discussed.
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PMID:Isolation of a peptido-polysaccharide from the dermatophyte Epidermophyton floccosum and a study of its reaction with human C-reactive protein and a mouse anti-phosphorylcholine myeloma serum. 88 87

An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.
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PMID:[Prognostic factors and monitoring of myeloma]. 128 67

A sensitive enzyme-linked immunosorbent assay of human interleukin-6 (IL-6) was developed to measure the serum IL-6 by Fujirebio INC. Its sensitivity was 3 pg/ml and its analytical range was from 3 to 200 pg/ml. Its precision, reproducibility, and sensitivity were quite satisfactory. The serum IL-6 levels in 200 normal individuals were less than 3 pg/ml. Serum IL-6 concentration in patients with malignant and benign monoclonal gammopathy (BMG) was determined by an ELISA. Serum IL-6 concentration in patients with Bence Jones protein (BJP) type multiple myeloma (MM) (n = 12) was 12.3 +/- 12.7 (mean +/- SD) pg/ml, BJP and IgG type MM (n = 4) 11.5 +/- 5.8 pg/ml, IgM type MM (n = 11) 11.1 +/- 17.5 pg/ml and IgA type MM (n = 4) 4.0 +/- 1.4 pg/ml. They were significantly higher in BJP, BJP and IgG, and IgM types than in normal individuals. The cases with the serum IL-6 of more than 10 pg/ml were move frequent in MM (32.8%) than in BMG (16.3%). The correlation between the serum IL-6 and C-reactive protein (CRP) was r = 0.563 in patients with MM (n = 61) and r = 0.498 in BMG (n = 43). Besides, during the clinical course of a patient with IgG-lambda and BJP-lambda type MM, serum IL-6 concentration responded more sharply than CRP and WBC on candida infection. The measurement of serum IL-6 therefore, seemed not useful for differential diagnosis of monoclonal gammopathies, but it seemed useful as an acute phase protein as well as CRP.
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PMID:[Determination of serum interleukin-6 concentration by an enzyme-linked immunosorbent assay in patients with paraproteinemia]. 151 81

In multiple myeloma (MM), an overproduction of IL-6, indicated by increased plasma C-reactive protein levels, is found in 37% of MM patients at diagnosis and is associated with disease aggressiveness, myeloma-cell proliferation, and poor prognosis. IL-6 is produced by the tumoral environment mainly and not by myeloma cells themselves. IL-6 is a major growth factor for malignant plasmablastic cells in vitro, and it is possible to reproducibly obtain IL-6-dependent myeloma-cell lines. Moreover, anti-IL-6 therapies in patients with terminal disease block myeloma-cell proliferation in vivo. The myeloma-cell growth factor activity of IL-6 is probably the consequence of IL-6 being a growth factor for normal plasmablastic cells. Hematopoietic cytokines (GM-CSF, IL-3, IL-5, G-CSF) synergize with IL-6 to support myeloma-cell proliferation. IFN-alpha and TNF induce an autocrine production of IL-6 in myeloma-cell lines and make possible the autonomous growth of these cell lines. On the contrary, IFN-gamma completely inhibits the IL-6-mediated myeloma-cell proliferation. The identification of some major cytokines involved in the control of the myeloma clone has immediate therapeutic implications, because some of these cytokines are, or might be, used in the treatment of patients with MM.
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PMID:Cytokine network in human multiple myeloma. 158 74

C-reactive protein (CRP) is a major acute phase reactant in most mammalian species. CRP molecules from all species display Ca2(+)-dependent binding to phosphorylcholine (PC). The conserved PC-binding region of CRP corresponds to amino acids 51-66 within the human CRP sequence. A synthetic peptide composed of residues 47-63 of human CRP was previously shown to possess PC binding activity. The charged amino acids at positions 57, 58, 60, and 62 of this synthetic peptide were critical for PC-binding based on lower binding activity of synthetic peptides containing uncharged residues at these positions. The PC-binding peptide was used to generate mouse mAb that were tested for reactivity with intact CRP and with the TEPC-15 (T-15) mouse myeloma protein that also binds PC. The PC-binding peptide of CRP was recognized by two mAb specific for the T-15 Id. One of the mAb generated against the PC-binding peptide of CRP (IID6.2) recognized an epitope on the T-15 protein that was also recognized by the near-binding site-specific mAb (F6) to the T-15 PC-Id. Binding of IID6.2 to T-15 myeloma protein was not inhibited by PC and did not require Ca2+; however, binding was inhibited by the synthetic PC-binding peptide itself. Recognition of synthetic peptides containing uncharged amino acid substitutions by mAb F6 and IID6.2 was greatly reduced indicating that the shared epitope on T-15 and CRP was composed of similar charged residues. Therefore, CRP displays the same idiotope as an antibody that shares its specificity for the hapten, PC.
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PMID:A synthetic peptide corresponding to the phosphorylcholine (PC)-binding region of human C-reactive protein possesses the TEPC-15 myeloma PC-idiotype. 170 98

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.
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PMID:Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. 171 18

A radioimmunoassay (RIA) for the determination of human group-II phospholipase A2 (M-PLA2) has been developed. M-PLA2 was purified from human spleen. Monoclonal antibody (IgG) was prepared by fusion of splenic cells from immunized mice with M-PLA2 and the mouse myeloma cell line NS-1. The RIA was carried out by a single antibody method. The assay is sensitive (0.78 micrograms/l), reproducible and specific. In healthy individuals, the serum M-PLA2 concentration ranges from 1.4 to 4.2 micrograms/l, the average being 2.2 +/- 0.1 micrograms/l (mean +/- SE). Using the RIA, we found increased serum M-PLA2 in patients with various infections and malignant tumors. We also showed the postoperative transient elevation of serum M-PLA2 in cases without any infectious complications. The elevation was independent of the surgical procedure or site. The maximum serum M-PLA2 level was seen on the 2nd to 4th postoperative day. In these patients, the serum M-PLA2 and C-reactive protein levels were significantly correlated. The present study indicated that serum M-PLA2 is an acute phase reactant.
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PMID:Development of a radioimmunoassay for human group-II phospholipase A2 and demonstration of postoperative elevation. 172 81

A 58-year-old female was admitted to our hospital because of anemia in March 1987. Monoclonal protein (IgA, kappa) was detected and a diagnosis of multiple myeloma was made. Partial remission was obtained after VAD therapy with alpha-interferon. In December 1989, she was readmitted because of a pathological fracture of the left humerus. A white blood cell count was 4400/microliters with 30% myeloma cells and the urine protein (Bence Jones protein) was 26 g/day. Systemic chemotherapy was not effective. She developed pleural and pericardial effusions, bone mass, disturbance of consciousness and died of respiratory failure only 3 months after readmission. The pleural and pericardial fluids contained many myeloma cells. c-myc gene rearrangement was detected in myeloma cells obtained from the pleural fluid using c-myc exon1 and exon2 probes. The levels of interleukin-6 (IL-6) measured by ELISA was 107.4 pg/ml in serum, 56.2 pg/ml in pleural fluid and 780.0 pg/ml in pericardial fluid. Because of the lack of any overt infectious focus, the level of IL-6 appears to have been related to aggressive proliferation of myeloma cells. It was of interest that C-reactive protein, induced by IL-6, was a good marker reflecting disease activity.
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PMID:[A high serum level of interleukin-6 in a patient with aggressive multiple myeloma]. 175 53

Human C-reactive protein (CRP) is an acute phase reactant that is opsonic and an activator of macrophage tumoricidal function. CRP also activates the classical C cascade. These activities suggest that CRP might interact with monocytes/macrophages via specific receptors in a manner analogous to the interaction of IgG with FcR. With the use of radio-labeled human CRP, we have observed specific binding of CRP to human blood monocytes and the human monocytic cell line U-937. Binding was saturable at a pathophysiologic concentration of CRP, with an estimated KD of 9.5 x 10(-8) M and 3.6 x 10(5) binding sites/cell. Specific binding was inhibited by polyclonal human IgG as well as an IgG1 myeloma. In the converse experiment, CRP failed to inhibit specific [125I]IgG binding. The mAb IV.3, which inhibits binding of IgG immune complexes to FcRII, did not inhibit CRP binding. A 100-fold excess of phosphorylcholine or the phosphorylcholine binding peptide of CRP (residues 47-63) failed to inhibit binding. Although human rIFN-gamma and PMA increased FcRI expression, these reagents had no affect on CRP receptor expression. A single membrane protein of 38 to 41 kDa from U-937 cells was chemically cross-linked to [125I]CRP; the cross-linking was inhibited by human IgG1 but not the IV.3 mAb. Furthermore, two membrane proteins with a Mr of 38 to 40 kDa and 58 to 60 kDa were isolated by CRP ligand-affinity chromatography. These proteins were of a distinct size from those isolated for FcRI from an IgG ligand matrix. These studies demonstrate specific binding of human CRP to a human monocytic cell line via receptors that are distinct from the IgG FcR and implicate CRP in nonspecific, preimmune host defense reaction mediated by cells of the monocytic lineage.
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PMID:Characterization and isolation of a C-reactive protein receptor from the human monocytic cell line U-937. 215 64


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