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)

Successful therapy for a case of multiple myeloma with a spontaneously crystallizing cryoglobulin of the IgG2-kappa light chain variety was achieved, using both continuous-flow cell centrifugation plasmapheresis to rapidly lower the M component and combination chemotherapy with phenylalanine mustard, prednisone, procarbazine, and vincristine to control the myeloma process. This resulted in resolution of incapacitating large and small necrotic cutaneous ulcerations of the extremities. Physicochemical studies of the crystalcryoprotein demonstrated that cryoprecipitation was rapid and accompanied by the formation of needle-shaped crystals, yet was completely reversible at 37 degrees C. Cryocrit determinations varied depending upon relative centrifugal forces and temperature and did not always relate linearly to the amount of abnormal protein, thus making these alone unreliable in assessing response to therapy.
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PMID:Successful therapy of crystalcryoglobulinemia: a case report. 11 18

A 76-year-old man with plasma cell leukemia was treated with L-phenylalanine mustard and prednisone (CLGB 7461). There was good partial remission of the plasma cell disease characterized by disappearance of the plasma cells in the peripheral blood, reduction of plasma cells in the marrow aspirates to less than 5% of the nucleated hematopoietic cells, a reduction in the serum monoclonal IgG from 7.6 to 2 gms/100 ml, and the disappearance of urinary monoclonal IgG, Bence-Jones protein and a complex of gamma-chain fragment and beta2-microglobulins. There was also a marked improvement in the renal function and a decrease in the proteinuria from 4+ to 1+. The patient relapsed after more than 8 months of response and failed to respond to subsequent treatment with cytoxan and cytosine arabinoside. However, the efficacy of standard myeloma therapy was clearly apparent in this case of plasma cell leukemia.
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PMID:Plasma cell leukemia: response to conventional myeloma therapy. 27 34

Amino acid sequence analysis of the pFc' fragment obtained by pepsin digestion of an IgG3; G3m(g) human myeloma protein HER shows it to consist of 112 residues. It starts at position 334 (gamma1 numbering), contains eight residues of the Cgamma2 region, and the whole Cgamma3 domain. Comparison with the sequence of gamma1 shows five differences including an extra Met at 397. Each is accountable by a single base substitution. The sequence is identical to that of a G3m(b0) molecule except for the previously noted allotype related Tyr/Phe exchange at position 436. The high degree of homology (95%) among gamma-chain subclasses suggests a recent diversification.
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PMID:The amino acid sequence of a human immunoglobulin G3m(g) pFc' fragment. 40

A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.
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PMID:Multiple myeloma complicating the course of seronegative systemic lupus erythematosus. 63 92

Magnetic-resonance techniques are used to refine the model of the combining site of the Fv fragment of the dinitrophenyl-binding mouse myeloma protein MOPC 315 constructed by Padlan, Davies, Pecht, Givol & Wright (1976) (Cold Spring Harbor Symp. Quant. Biol.41, in the press). Light-absorption studies indicate a dinitrophenyl-tryptophan interaction in the Fv fragment of the type occurring in free solution. The Dnp-aspartate-tryptophan complex is therefore used as a starting point for the n.m.r. (nuclear-magnetic-resonance) analysis of the dinitrophenyl-Fv fragment interaction. Ring-current calculations are used to determine the geometry of the complex. The specificity of complex-formation between dinitrophenyl and tryptophan is confirmed by the lack of ring-current shifts of the dinitrophenyl resonances when tryptophan is replaced by any other aromatic amino acid. Proton n.m.r. difference spectra (at 270MHz), resulting from the addition of a variety of haptens to the Fv fragment, show that the combining site is highly aromatic in nature. Calculations on the basis of ring-current shifts define the geometry of the combining site, which involves a dinitrophenyl ring in van der Waals contact with four aromatic amino acid residues on the protein. The observation of a nuclear Overhauser effect on the H((3)) resonance of the dinitrophenyl ring provides additional constraints on the relative geometry of the H((3)) proton and an aromatic amino acid residue on the Fv fragment. The specificity of the Fv fragment for dinitrophenyl ligands arises from a stacking interaction of the dinitrophenyl ring with tryptophan-93(L), in an ;aromatic box' of essentially tryptophan-93(L), phenylalanine-34(H) and tyrosine-34(L); asparagine-36(L) and tyrosine-34(L) also contribute by forming hydrogen bonds with the nitro groups on the dinitrophenyl ring. The n.m.r. results also confirm that the antibody-hapten reaction may be visualized as a single encounter step. An Appendix shows the method of calculation of ring currents for the four aromatic amino acids and their use in calculating structures.
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PMID:The combining site of the dinitrophenyl-binding immunoglobulin A myeloma protein MOPC 315. 92 44

From collected data on variable region sequences of heavy chains of immunoglobulins, the probability of random associations of any two amino-acid residues in the complementarity-determining segments was computed, and pairs of residues occurring significantly more frequently than expected were selected by computer. Significant associations between Phe 32 and Tyr 33, Phe 32 and Glu 35, and Tyr 33 and Glu 35 were found in six proteins, all of which were mouse myeloma proteins which bound phosphorylcholine (= phosphocholine). From the x-ray structure of McPC603, Tyr 33 and Glu 35 are contacting residues; a seventh phosphorylcholine-binding mouse myeloma protein also contained Phe 32 and Tyr 33 but position 35 had only been determined as Glx and thus this position had not been selected. Met 34 occurred in all seven phosphorylcholine-binding myeoma proteins but was also present at this position in 29 other proteins and thus was not selected; it is seen in the x-ray structure not to be a contacting residue. The role of Phe 32 is not obvious but it could have some conformational influence. A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant. The ability to use sequence data to locate residues in complementarity-determing segments making contact with antigenic determinants and those playing essentially a structural role would contribute substantially to the understanding of antibody specificity.
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PMID:Attempts to locate residues in complementarity-determining regions of antibody combining sites that make contact with antigen. 106 Nov 62

To study the expression of HLA-DQ beta chain alleles associated with type 1 diabetes, mAbs were generated from mice immunized with synthetic peptides representing allelic HLA-DQw7 and HLA-DQw8 beta chain sequences. The splenocytes from immunized mice were fused with myeloma cells, either immediately after or following additional in vitro boosting with peptide. Peptide-specific mAbs, predominantly of the IgG isotype, were isolated only from in vitro boosted splenocytes. Immunoblot analysis showed that several of the mAbs cross-reacted with DQ beta chain molecules. One mAb to a peptide representing DQw8 beta position [49-60] specifically recognised the DQw8 beta chain. Three mAbs to a peptide representing DQw8 beta position [39-52] specifically recognised an epitope consisting of Gly-Val-Tyr in position 45-47, i.e., all DQ beta alleles except DQw7 beta (position 45-47: Glu-Val-Tyr) and DQw2 beta (position 45-47; Gly-Glu-Phe). In FACS analysis these mAbs bound lymphocytes with the same specificity as found by immunoblotting analysis. Thus, by combining in vivo and in vitro immunization we have generated a number of epitope specific monoclonal IgG antibodies that distinguish closely related HLA-DQ beta chain alleles in predetermined positions.
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PMID:Production of epitope specific monoclonal IgG antibodies to HLA class II molecules by combining in vivo and in vitro immunization. 137 72

The ABPC 48 myeloma protein and the 3-14-9 mAb derive their V region genes from the same VH and V kappa gene families. They also share a cross-reactive idiotope defined by the anti-Id mAb IDA 10. Whereas ABPC 48 is specific for bacterial levan, 3-14-9 showed a significant Ag-binding activity to aminophenyl-beta-N-acetylglucosaminide (AZO). In order to define the molecular basis of idiotope expression and Ag-binding activity, we have cloned the genes encoding the 3-14-9 H and L chain V region genes, generated antibodies that carry mutations within the L chain genes, by site-directed mutagenesis, and investigated the effects of those mutations with respect to IDA 10 idiotope expression and binding to AZO. Our findings show that, whereas expression of the IDA 10-defined idiotope requires association of both the H and L chains, a single change (glycine to phenylalanine) at position 91 in the third complementarity-determining region of the L chain abolished both idiotope expression and Ag-binding activity. In addition, a L chain change of alanine to threonine at position 25 allowed idiotope expression to some extent but significantly reduced binding activity to AZO. These data suggest that a single amino acid change can play a crucial role in the functional activity and structural integrity of antibodies.
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PMID:A single amino acid mutation in CDR3 of the 3-14-9 L chain abolished expression of the IDA 10-defined idiotope and antigen binding. 138 May 35

Recombinant granulocyte colony-stimulating factor (rG-CSF) primed the ability of human neutrophils to generate increased levels of reactive oxidants in response to fMet-Leu-Phe, and also resulted in an increased rate of protein biosynthesis which was similar to that induced by granulocyte-macrophage colony-stimulating factor. However, rG-CSF reduced the chemotactic activity of neutrophils in response to endotoxin and did not result in an enhanced rate of killing of Staphylococcus aureus. rG-CSF was administered to patients after high dose chemotherapy and autologous bone marrow transplantation for the treatment of either Hodgkin's disease or multiple myeloma. This cytokine decreased the period of neutropenia following such treatment. Neutrophil function in two patients, measured seven days after the final administration of rG-CSF, was severely impaired as indicated by a greatly decreased ability to generate reactive oxidants. However, seven days later (i.e. 14 days post-therapy), the functional activity of the neutrophils from these patients had returned to normal. These data indicate that assays of neutrophil function together with morphological assessment of neutrophil numbers and maturity should be performed in order to evaluate the immune status of patients undergoing such therapy.
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PMID:Effects of recombinant human granulocyte colony-stimulating factor on neutrophil function in vitro and in vivo following chemotherapy and autologous bone marrow transplantation. 172 83

Peptichemio (PTC) is a mixture of six synthetic oligopeptides, each containing the alkylating agent m-di(2-chloroethyl)amino-phenylalanine. Freshly obtained myeloma cell infiltrated human bone marrow specimens were in parallel exposed to melphalan and PTC. The cytotoxic effect of the drugs on the myeloma cells of each specimen was measured by the differential staining culture method (DISC). PTC displayed higher cytotoxicity to the myeloma cells as compared to melphalan in all 12 cases analysed. The increase of the cytotoxic effect of PTC compared to melphalan varied between different cases. In melphalan resistant cases the cytotoxic effect of PTC as compared to melphalan was clearly significant (P = 0.001).
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PMID:Efficacy of peptide bound m-L-sarcolysin (peptichemio) on melphalan resistant human myeloma cells in vitro. 182 Apr 93


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