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 genome of hybridoma PTF-02 has two genes for the kappa chains, and only one of these codes for the synthesis of the antibody light chains. The nucleotide sequences corresponding to the leader peptide and to the variable region of this gene were determined. An amino acid sequence corresponding to exons has been proposed on the basis of the nucleotide sequence. A nucleotide sequence adjacent to the gene at the 5'-end has also been determined, in particular, the precise localization of TATA- and CAT-boxes as well as those of the conservative deca (dc) and pentadeca (pd) sequences. The structure of the regulatory region in the gene is similar to that in the myeloma genomes. However, the 5'-region differs in its nucleotide composition and in the frequency of dc sequences from the DNA sequences adjacent to the 5'-end of eukaryotic genes which do not belong to the immunoglobulin family.
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PMID:[The structure of the variable gene for the kappa chains of antibodies produced by hybridoma PTF-02]. 311 99

The monoclonal antibody 8A, which recognizes a human plasma cell-associated antigen, was covalently linked to xanthine oxidase in a conjugate maintaining both immunological and enzymatic properties. A significant degree of target cell lysis was obtained at an enzyme concentration that was ineffective on non-target cells and on myeloid staminal cells (CFU-GM). The cytotoxic activity was abolished by an excess of antibody, by allopurinol and by superoxide dismutase and catalase. A possible use of the conjugate for bone marrow purging in multiple myeloma patients is suggested.
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PMID:Selective cytotoxicity of an oxygen-radical-generating enzyme conjugated to a monoclonal antibody. 326 64

Legionellae are widely spread in natural and man-made habitats. In many instances contaminated tap water has been linked to sporadic or endemic cases of human pulmonary infections, but it is not known why, in spite of frequent occurrence, legionellae only rarely cause disease. Monoclonal antibodies against Legionella pneumophila serogroup 1 (Philadelphia 1) were prepared in order to distinguish between subtypes of this serogroup. Balb/c mice were immunized i.v. three times with heat inactivated bacteria. Antibody formation was detected by an enzyme-linked immunosorbent assay (ELISA) technique using peroxidase-conjugated antimouse IgG. Spleen cells were then fused with NS-1 myeloma cells and cloned by limiting dilution. Four monoclonal antibodies were studied in detail. The study included 47 strains of L. pneumophila: 19 strains were of human origin and 28 were isolated from different environmental sources. Most were from tap water, but none from natural habitats. All strains belonged to serogroup 1 as defined by direct immunofluorescence (DFA) using monospecific FITC-labelled polyclonal antisera from rabbits. The strains were further characterized by beta-lactamase production, activity of catalase, oxidase and proteases, analysis of ubiquinones, and demonstration of membrane protein patterns by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A strong homogenicity between all the strains could be revealed by these methods independent of their origin. One of the monoclonal antibodies (B-1) was able to distinguish between human and environmental isolates. Eighteen of the 19 human strains reacted very strongly in DFA using antimouse immunoglobulin. No reaction, however, was seen with all of the environmental strains. Immunoblots were performed for characterization of the distinguishing feature using membrane complexes of all strains on nitrocellulose strips. The blots were incubated with antibody B-1, and immune complexes were detected by 125I-protein A. Broad intense blackening was seen between 22 and 70 kilodalton. This result suggests that no single protein, but rather a smaller component such as an oligosaccharide attached to constituents of different molecular weights, might be responsible for the discriminating reaction.
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PMID:Discrimination between clinical and environmental strains of Legionella pneumophila by a monoclonal antibody. 353 65

Two new human myeloma cell lines have been established from a 36-year-old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortisone, and 2-mercaptoethanol and designated as M-3 medium. Two IgG kappa cell lines, LB -831 and LB-832, were established and proved to be Epstein-Barr virus negative using the internal repeat sequence DNA probe. Characteristic plasma cell morphology was evident by light and electron microscopy. Immunotyping revealed an IgG kappa , B1+, B2-, Ia (HLA-DR)+, CALLA+ phenotype for each cell line as well as for the original pleural fluid and bone marrow myeloma cells. The supernatants also contained IgG kappa, beta 2 microglobulin, and large amounts of osteoclast-activating factor (indicating bone-resorbing activity). Cytogenetic analysis of the LB-831 cell line revealed a nearly triploid highly abnormal karyotype with numerous clonal chromosomal abnormalities involving chromosomes 1, 3, 5, 7, 13, and 15; several structurally abnormal marker chromosomes; and a putative homogeneously staining region on chromosome 7p at band p22. Analysis of the LB-832 cell line revealed several additional clonal abnormalities. These additional cytogenetic changes suggest that in vivo sequential clonal evolution occurred in this patient. Therefore, two new but related cell lines have been established, which should prove useful for further biological studies.
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PMID:Establishment of two new myeloma cell lines from bilateral pleural effusions: evidence for sequential in vivo clonal change. 392 97

In the course of transient expression studies undertaken to determine the location of the mouse CD8b gene promoter, two additional promoter activities were detected within 600 nucleotides upstream of the gene. One activity directs transcription in the same direction as CD8b but fails to transcribe the CAT reporter gene due to an apparent transcription-blocking element lying between it and the gene. The second activity directs transcription opposite to that of the CD8b gene. Northern hybridization with a probe consisting of nucleotides -875 to -550 relative to the site of CD8b transcription initiation revealed hybridizing species of 4 kilobases (kb) and 1.8 kb in poly-A-selected RNA from mouse thymus but not from any other tissues. Similar RNA species were detected in poly-A+ RNA from concanavalin A-stimulated spleen cells and several long-term CTL lines but not from the EL4 or BW5147 T-cell lines or the J558L myeloma. The mRNA species were most abundant in cells of a secondary mixed leukocyte culture which were greater than 95% CD8(+). Northern hybridizations using single-stranded unidirectional probes indicated that these mRNAs represent transcription opposite to the CD8b gene. The tissue and cell type distribution of this newly-discovered gene (designated Bop for CD8b opposite) are consistent with T-cell-specific and possibly CD8-positive T-cell-specific expression. The head-to-head arrangement of the Bop and CD8b genes is reminiscent of the arrangement of the Tap1 and Lmp2 genes, and the expression of the Bop gene in CD8-positive cells raises the possibility that these genes are involved in the same functional pathway.
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PMID:Bop: a new T-cell-restricted gene located upstream of and opposite to mouse CD8b. 759 Sep 68

In addition to E mu, several elements downstream of the IgH cluster, i.e. 3' of the C alpha gene, are involved in regulating IgH gene rearrangement and expression. This entire downstream regulatory region was shown to be deleted in the mutant myeloma cell line, LP1.2. The deletion encompasses approximately 34 kb and is presumably responsible for the reduced levels of IgH expression in this cell line. An additional regulatory element, included in the LP1.2 deletion, was identified by investigation of a DNase I hypersensitivity site located approximately 33 kb downstream of the alpha gene and present in pre-B and plasma cells. This novel IgH gene enhancer element, termed 3' alpha-hs4, is capable of activity throughout B cell development. Transient transfection of 3' alpha-hs4 in a CAT reporter gene construct shows transcriptional enhancement activity approximating that of E mu in S194 plasmacytoma and M12.4.1 and A-20 B cell lines; while in a pre-B cell line, 18-81, the average activity is 25% that of E mu. Enhancer activity was localized to an 800 bp fragment. The activity of 3' alpha-hs4 is orientation independent and appears to be B cell specific. Tight regulation of 3' alpha-hs4 is inferred from its variable activity in different plasmacytoma cell lines and within the pre B cell line, 18-81.
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PMID:Identification of 3' alpha-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation. 773 12

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

We report here that cultured human lymphoma cells in the absence of sonicated eosinophils are sensitive to killing by glucose oxidase (beta-D-glucose:oxygen-oxido reductase; EC 1.1.3.4) at concentrations as low as 0.025 microgram/ml, a level that can be rapidly attained in s.c. tumor implants in mice that receive a single nonlethal injection of enzyme. Multiple clonogenic assays were used to measure the survival of human lymphoma cell lines (H9 and ARH-77) cultured for 14 days in complete RPMI 1640 supplemented with exogenous glucose oxidase (0.025-2.5 micrograms/ml) or an immunoconjugate containing glucose oxidase (0.25-25 micrograms/ml) in the presence or absence of catalase (10 micrograms/ml) or an equal number of sonicated human eosinophils with or without supplemental 100 microM Br-, I-, or SCN-. In addition, we used an immunoassay to measure the concentration of glucose oxidase in s.c. implants of the Sp 2/0 myeloma tumor at 0-30 min after an i.v. injection of 50 micrograms of enzyme into 21 BALB/c mice. Doses of glucose oxidase as small as 0.025 microgram/ml killed more than 3 logs of tumor cells. Catalase completely inhibited, and sonicated human eosinophils partially inhibited, the killing by glucose oxidase or immunoconjugate, whereas supplemental halides had no effect. Glucose oxidase i.v. produced levels > 0.04 microgram/g of tumor for 30 min after injection with a peak concentration of 0.079 microgram/g of tumor within 5 min of injection. These results are important because certain human lymphomas contain extensive extracellular deposits of eosinophil peroxidase, thereby making these tumors potentially less susceptible to killing by otherwise therapeutic doses of glucose oxidase.
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PMID:Effects of sonicated eosinophils on the in vitro sensitivity of human lymphoma cells to glucose oxidase. 816 93

The 5'-upstream region (1.3 kb) of the gene encoding the POU domain transcription factor Oct-1 was cloned and sequenced. CAT reporter gene analysis of this region has detected a functionally active promoter. This region contains 24 TAAT-core sites, arranged in five clusters (four to six sites in one cluster); two octamer sites (ATGCAAAT) are located in the first and second clusters; in the second one the CCAAT-box adjacent to the octamer overlaps with the TAAT-core site. As shown by gel retardation assay, Oct-1, Oct-2, and some unknown proteins from myeloma cell line NS/0 interact with the TAAT-core sites of these clusters. The results suggest autoregulation of Oct-1 gene expression that may also be controlled by other POU proteins, homeodomain proteins and CCAAT trans-action factors.
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PMID:Oct-1 promoter region contains octamer sites and TAAT motifs recognized by Oct proteins. 959 83

Syndecan-1 (CD138) is a cell membrane proteoglycan that binds extracellular matrix components and various growth factors. The role of syndecan-1 in the control of cell growth and morphology has been illustrated by its altered expression in hematological malignancies such as multiple myeloma as well as some solid tumors. It has been reported that the expression of syndecan-1 in cells of the B lineage is developmentally regulated such that pre-B cells and plasma cells express syndecan-1 while mature B cells do not. Thus, we investigated whether the proximal promoter region of the murine syndecan-1 promoter was able to confer the observed on-off-on expression of syndecan-1 in cells of the B lineage as they develop from pre-B cells to plasma cells. Experiments carried out using deletion mutants of the proximal promoter cloned upstream of the CAT reporter gene transfected into murine cell lines, representing the above stages of B-cell development, such as BA/F3 (pro-B cell), 70Z/3 (pre-B cell), 2PK3 (late mature B cell), and MPC-11 (plasma cell), showed detectable levels of CAT expression. The WEHI-231 (mature B cell) cell lines did not show detectable levels of CAT reporter activity. The strong levels of expression were observed with a fragment of the proximal promoter spanning the region from -365 to -95 (from the translation start point). However, Northern analysis of RNA obtained from the five murine B-cell lines, representing various stages of B-cell development, showed that the 70Z/3, MPC-11 but not BA/F3, and 2PK3 cells expressed detectable levels of syndecan-1 mRNA. By FACS analysis, using a rat anti mouse syndecan-1 antibody, syndecan-1 expression on the cell surface was found to correlate with the observed mRNA expression patterns in these cell lines. Our results indicate that the proximal promoter of the murine syndecan-1 promoter is not sufficient for the observed developmental pattern of syndecan expression in B cells.
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PMID:Proximal promoter of the murine syndecan-1 gene is not sufficient for the developmental pattern of syndecan expression in B lineage cells. 1127 53


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