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)

An expression vector (pIL-2/IgG1) was constructed with the coding sequence of human IL-2 inserted upstream of the four exons (CH1, hinge, CH2, and CH3) that encode the human IgG1 H chain constant region. Introduction of this vector into a nonsecreting murine myeloma cell line resulted in the production of a chimeric molecule (IL-2/IgG1) consisting of IL-2 attached to the three Ig constant region domains. This molecule was secreted by the transfectant as a homodimer. Functional characterization revealed that the IL-2/IgG1 chimeric molecule exhibited the binding and proliferation-mediating activities of IL-2. On a per molecule basis, IL-2/IgG1 was indistinguishable from human rIL-2 in the ability to induce the proliferation of an IL-2-dependent T cell line. This chimeric molecule also possesses Ig effector function, in that it can mediate the specific lysis of IL-2R-positive cells in the presence of complement. These results demonstrate that it is possible to maintain Ig effector function in molecules ("immunoligands") in which the binding specificity is conferred not by Ig variable regions, but rather, by a ligand of choice.
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PMID:A chimeric IL-2/Ig molecule possesses the functional activity of both proteins. 198 2

We measured superoxide scavenging activity (SSA) of erythrocytes with the recently developed chemiluminescence method by Nakano et al in Down syndrome and various hematological diseases. Hematological disorders were aplastic anemia, myelodysplastic syndrome, multiple myeloma, malignant lymphoma and chronic myelogenous leukemia. The SSA of erythrocytes was 1.7 times higher in Down syndrome, which was consistent with values reported in the previous publications. The erythrocyte SSA in patients of multiple myeloma treated with interferon-alpha was higher than that in healthy volunteers. The erythrocyte SSA in myelodysplastic syndrome, malignant lymphoma and chronic myelogenous leukemia did not differ from that in healthy volunteers. The mean value of erythrocyte SSA in aplastic anemia also remained within normal range. However, when an individual's hemoglobin concentration was compared with his or her own erythrocyte SSA, there was a clear correlation between them. Namely erythrocyte SSA increased when anemia was severe. There was no correlation between erythrocyte SOD activity and ageing.
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PMID:Erythrocyte superoxide dismutase in various hematological diseases. 215 34

Transfection into lymphoid cells of a chimeric T-cell receptor-immunoglobulin gene has been used to generate a secreted water-soluble form of the variable (V) domain of a human T-cell receptor alpha chain for use in structural (i.e. x-ray crystallographic) studies. The chimeric protein consists of the V alpha region of the T-cell receptor of a diphtheria toxoid-specific human T-cell clone fused to a human immunoglobulin kappa light chain constant (C) region. It is efficiently secreted by myeloma cells as a noncovalent homodimer of 65-kDa molecular mass in the absence of either immunoglobulin heavy or light chain. The V alpha C kappa protein is extensively glycosylated, and its secretion is glycosylation-dependent. Chimeric genes containing the V beta region of this particular T-cell receptor linked to immunoglobulin C kappa or C gamma 2 regions are expressed intracellularly, but the products, although glycosylated, are not secreted, nor do they assemble with the V alpha C kappa protein. This suggests that the chimeric beta chain-immunoglobulin proteins are incorrectly folded and/or processed due either to the design of the gene fusions themselves or to the absence of vital T-cell-specific accessory molecules in the myeloma host.
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PMID:Secretion of a homodimeric V alpha C kappa T-cell receptor-immunoglobulin chimeric protein. 252 93

We previously purified the murine transferrin receptor from cultured myeloma cells and determined the amino acid sequence of six tryptic peptides. We now report the cloning of cDNA encoding the murine transferrin receptor. A tryptic peptide containing a region of six consecutive amino acids, all encoded by four or fewer codons, was used to design two overlapping oligonucleotide probes, 17 and 14 nucleotides in length. These probes were used to screen a lambda gt10 cDNA library from NS-1 myeloma cells. Of approximately 400,000 plaques screened, two hybridized strongly to both probes. A subfragment of one clone that hybridized with both oligonucleotide probes was found to encode the tryptic peptide from which the probes were derived, as well as another sequenced tryptic peptide. Comparison of the sequence with that of the human transferrin receptor shows a high degree of conservation of the sequences surrounding and penetrating the membrane, including cysteine residues that may be involved in interchain disulfide bonding and/or covalent attachment of lipid. The current data, when combined with the published sequence of the human receptor, allow assignment of all six tryptic peptides to a single chain, supporting the idea that the receptor is a homodimer. A 4.9-kb messenger RNA was found in several cultured murine and human tumor cell lines, but transferrin receptor messenger RNA was not detectable in murine spleen. An additional RNA species of 2.7 kb was present in approximately equal abundance in the murine myelomas NS-1 and C118 but was absent from T lymphomas TIKAUT, ST-1, and ST-4.
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PMID:cDNA cloning of the murine transferrin receptor: sequence of trans-membrane and adjacent regions. 298 91

We have analyzed cells of the B lineage for expression of the Tp44 antigen, a 44,000 homodimer detected by monoclonal antibody 9.3 on approximately 80% of mature human T lymphocytes. Previous evidence has suggested that Tp44 may function as a receptor for accessory signals in T cell activation. High level Tp44 expression was observed on plasmacytomas grown in cell culture and on plasma cells from bone marrow biopsies of multiple myeloma patients. This antigen is not present on resting B cells from either peripheral blood or lymphoid organs, or on any other B cell tumor. The growth kinetics and Ig production in plasmacytomas are not affected by the binding of antibody 9.3. Moreover, the Tp44 molecule is co-expressed with PCA-1, an antigen characteristic of plasma cells, on peripheral blood B cells stimulated in vitro to differentiate toward plasma cells. Tp44 may represent a later stage of B cell differentiation than PCA-1 because unlike the PCA-1 antigen, this molecule could not be detected on any EBV-transformed cell line or Burkitt's lymphoma lines. The m.w. of the Tp44 molecule expressed on plasma cells and on T cells is identical, as determined by immunoprecipitation of radioiodinated cell surface proteins with monoclonal antibody 9.3. This antigen might be useful in studying the mechanism of growth and differentiation of human B cells, the heterogeneity within plasma cell populations, and B cell interactions with other components of the immune system.
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PMID:Tp44 molecules involved in antigen-independent T cell activation are expressed on human plasma cells. 303 21

A study correlating the presence of bovine isozymes in mouse myeloma/calf hybridomas with specific banded chromosomes of their bovine complement has enabled tentative assignments to be made of the bovine isozyme locus for peptidase C (PEP C) to chromosome 5 and the syntenic group lactate dehydrogenase B/peptidase B (LDH B/PEP B) to chromosome 19. There was some evidence for the association of LDH A with one of the last seven small pairs (23-29) of the complement and of superoxide dismutase 1 (SOD 1) with chromosome 13.
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PMID:Chromosome mapping in cattle using mouse myeloma/calf lymph node cell hybridomas. 638 Apr 91

Hybridomas were made between NS1/1-Ag4-1 mouse myeloma cells and spleen and lymph node cells from a sheep immunized with sheep red cells (RBC). The hybrid colonies grew well in culture but there was a substantial loss of sheep chromosomes. No hemolytic or agglutinating antibodies were detected in the culture supernatants after the 17th day following fusion, but immunofluorescence tests indicated that a few of the cells may have been expressing sheep IgG. Cytogenetic comparison of cells grown with and without HAT medium provided evidence that the enzyme HGPRT is located on the X chromosome of sheep as it is in man and mouse. Hybridoma isozyme patterns of esterase, G6PD, 6PGD, NP, LDH and SOD tested between the 63rd and 71st day of culture were like those of NS1; NP and LDH also showed zones that probably came from the sheep component.
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PMID:Culture of sheep X mouse hybridoma cells in vitro. 682 96

Alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) exhibited potent cytotoxic action on SP 2/0 mouse myeloma cells in vitro. Both SOD and vitamin E could inhibit the action of ALA and EPA indicating a role for reactive oxygen species and lipid peroxides. In addition, both ALA and EPA enhanced the formation of superoxide anion, hydrogen peroxide and lipid peroxides, and caused a reduction in the levels of antioxidant enzymes: SOD, catalase and glutathione peroxidase and induced significant damage to DNA in SP 2/0 cells. Thus, ALA and EPA inhibit antioxidant defenses of the cell and damage the DNA, which can ultimately lead to tumor cell lysis.
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PMID:Free radical-dependent suppression of growth of mouse myeloma cells by alpha-linolenic and eicosapentaenoic acids in vitro. 775 58

Alterations of NF-kappaB family members have been found to be associated with various forms of lymphoid malignancies. In order to determine whether alterations of the RelA gene are involved in lymphomagenesis, we analysed a large and representative panel (200 cases) of such tumors. Southern blot analysis did not reveal any rearrangements or locus amplification, suggesting that structural alterations of the RelA gene may represent rare events in lymphoid neoplasia. By means of PCR-SSCP analysis, we were able to identify a single point mutation leading to amino acid substitution (codon 494, Glu-Asp) in the transactivating (TA) domain in one case of multiple myeloma. The mutated allele was expressed in the pathological bone marrow sample but not in the peripheral blood cells of the patient. We demonstrate that the RelA protein carrying this specific mutation (called RelA494D) has less transactivating ability than the normal RelA protein. Interestingly, the mutated protein has a lower affinity for kappaB binding sites both as a homodimer or in association with the NFKB1/p50 subunit. Transfection experiments using a Gal4-RelA494D fusion protein indicated that the mutation does not alter the intrinsic transactivating ability of the TA domain of RelA. Furthermore, in vitro translated RelA494D is able to dimerize efficiently with other NF-kappaB members, such as p50, cREL and Ikappa Balpha. Our data therefore suggest that this mutation may alter the specific structural conformation needed for the DNA interaction of RelA, and provide insights into the amino acid sequences involved in mediating the biological activities of RelA.
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PMID:Identification of a tumor-associated mutant form of the NF-kappaB RelA gene with reduced DNA-binding and transactivating activities. 904 86

While in vivo gene inoculation is being increasingly exploited to express genes of choice and elicit specific immune responses in animal models, the utility of this method has not been explored extensively for the expression of antibody genes. The primary constraint of this method is the need to deliver to, and express in, a single cell two functional genes, i.e., those encoding heavy and light chains of an antibody molecule. Several single-gene constructs encoding variants of the monoclonal antibody (MAb) CC49 have been developed, MAb CC49 recognizes a tumor-associated glycoprotein, TAG-72. SP2/O myeloma cells, transfected with the CC49 single gene, express a single-chain protein which is secreted by the transfectoma as a homodimer. Following intramuscular injection of mice with the expression plasmids of the single-gene constructs, the encoded CC49 antibody (AB1) was detected in the plasma of the host. In addition, cellular and humoral immune responses to AB1 have been demonstrated. Antibodies (AB2) to the in vivo-produced variable region of AB1 have been detected and persisted for at least 70 days post-inoculation of the recombinant plasmid. Thus, in vivo gene inoculation of single-chain immunoglobulins may be an alternative or complimentary approach to the induction of anti-idiotypic responses in immunotherapy protocols.
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PMID:In vivo gene inoculation of a recombinant single-chain antitumor antibody induces anti-immunoglobulin response. 925 11


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