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)

Mouse thymuses with more than 99% T cells have been reported to contain immunoglobulin kappa mRNA-like molecules (kappa RNA) in relatively large quantities. The present study was undertaken to rule out the possibility that the kappa RNA was mainly a product of a few contaminating B cells of the thymus and to determine whether all T-cell subpopulations contained kappa RNA. By in situ hybridization with DNA complementary to kappa mRNA (kappa cDNA) the following observations were made: 98.5% of thymus cell preparations hybridized with kappa cDNA; the 1.5% unlabeled cells were generally larger and paler staining than the majority of thymus cells. Only 0.015% of thymus cells were intensely labeled and appeared to be plasma cells. Also, 87% of spleen cells hybridized with kappa cDNA; most of these showed similar labeling intensity to the majority of thymus cells. The number of unlabeled cells corresponded to the percentage of hemopoietic cells and macrophages in the spleen. Spleen cells in the range of 0.37-0.85% were intensely labeled and appeared to be plasma cells. The following controls supported the conclusion that the results with thymus and spleen were due to specific hybridization: most of the kappa mRNA-deficient tissue culture cells of the plasmocytoid tumor ABPL-4 did not hybridize with kappa cDNA. The kappa mRNA-producing cells from myeloma PC 3741 hybridized in situ with kappa cDNA. Furthermore, all cells from this tumor and all spleen cells hybridized uniformly with a cDNA probe complementary to most of the total cellular poly(A)-containing RNA species of these cells. These results indicate that T cells of all types in the thymus as well as in the periphery contain substantial quantities of kappa RNA.
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PMID:Direct demonstration of immunoglobulin kappa chain RNA in thymus T cells by in situ hybridization. 9 43

Endonuclease EcoRI-digested DNAs from BALB/c mouse embryos and MOPC 321 (a kappa chain secretor) myeloma were fractionated by agarose gel electrophoresis, and the DNA fragments containing part or all of the MOPC 321 kappa chain structural gene sequences were visualized by the Southern gel blotting technique using as the hybridization probes pCRI plasmids containing all or part of the enzymatically synthesized cDNA transcripts of the MOPC 321 kappa chain mRNA. The clear differences observed in the hybridization patterns of the two DNAs are in agreement with our previously reported results obtained with endonuclease BamHI and confirms that the sequence arrangement of kappa chain genes is different in the embryo and myeloma cells. We have cloned most of the kappa-sequence-positive EcoRI DNA fragments in Charon 4A phage by using the highly efficient in vitro phage lambda DNA packaging method, and we have characterized the cloned mouse DNA sequences by agarose gel blotting and R-loop mapping in electron microscopy. These studies identified, among others, one EcoRI DNA fragment which contains both variable and constant immunoglobulin kappa-gene sequences and is present only in the myeloma DNA. The two sequences are separated by a 2.8-kbase intron. We tentatively conclude that the kappa gene sequences on this DNA fragment underwent somatic rearrangement.
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PMID:DNA clones containing mouse immunoglobulin kappa chain genes isolated by in vitro packaging into phage lambda coats. 10 55

MPC 11 mouse myeloma cells synthesize two immunoglobulin kappa light chains, coded by two separate genes. One of these Kappa-chains has no variable region and is degraded intracellularly. The other is a full-length kappa-chain contaning both variable and constant regions: this chain is secreted, both by itself and combined with heavy chains in molecules of immunoglobulin G. This paper reports the amino acid sequence of the myeloma MPC 11 full-length kappa-chain. The chain is unusual in having 12 extra residues at its N-terminus when its sequence is aligned with those of other mouse kappa-chains; no other anomalies were found in its sequence.
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PMID:Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC 11. 41 75

We investigated by molecular hybridization whether T cells contain RNA sequences homologous to RNA which codes for immunoglobulin kappa-chain (k-chain). A radioactive probe of complementary DNA (cDNA) was prepared by transcription of purified k-chain mRNA from mouse myeloma MOPC-41 with reverse transcriptase (RNA-dependent-DNA nucleotidyltransferase) from avian myeloblastosis virus. The cDNA probably corresponded only to the constant region and 3'-terminus of k-chain mRNA. Kappa-chain cDNA was found to hybridize efficiently with RNA from both thymus cells and an established culture of thymoma cells. The thymus and thymoma cells contained 99.8% and 100% theta-positive cells, respectively. Quantitatively the average thymus T cell (thymus derived lymphocyte) contained about one half as much k-chain mRNA as the average spleen B cell ("bursa" dependent lymphocyte), whereas the thymoma cells contained only 1/33 as much. Control hybridizations of k-chain cDNA with myeloma and liver RNA support the conclusion that T cells in the thymus and in the thymoma cell line synthesize k-chain mRNA-like molecules. The thermal stability of hybrids of k-chain cDNA with RNA from spleen, thymus, thymoma, and another k-chain producing myeloma tumor was lower than that with MOPC-41 RNA. This finding may be due to the existence of several slightly different ck genes in the mouse as suggested by various control experiments.
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PMID:Sequences related to immunoglobulin kappa chain messenger RNA in T cells. 82 Oct 55

About 15% of monoclonal components or paraproteins are associated with malignancy when detected by simple electrophoresis on cellulose acetate membranes or agarose gel followed by protein staining. More sensitive methods for detecting monoclonal components result in a lower frequency of association with recognisable underlying disease. The sensitivity is dependent on the system used. Isoelectric focusing is 10 to 40 times more sensitive than simple electrophoresis at detecting monoclonal components. Electrophoretically separated bands may be quantitated densitometrically and at the present time this is the most satisfactory method for measuring monoclonal component concentration. Immunochemical methods for quantitating monoclonal components are limited by failure to react in a similar manner to polyclonal standards and giving problems of antigen excess resulting both in falsely elevated and low results. Electrophoretic methods must always be used in conjunction with these. The normal polyclonal ratio of immunoglobulin kappa:lambda light chain is disturbed by the presence of a monoclonal component. In 260 patients with myeloma we found that serum electrophoresis alone detected 90% while a disturbance in the kappa:lambda ratio detected 98%. However, 50% of monoclonal components less than 3 g/L were missed. Log kappa:lambda ratio correlates well with the densitometric scan of monoclonal components, both in vitro and in patients being monitored for treatment response in myeloma. This approach may complement or even replace densitometry for this purpose in the future.
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PMID:Electrophoresis and densitometry of serum and urine in the investigation and significance of monoclonal immunoglobulins. 219 91

Using a 15-nucleotide primer specific for the immunoglobulin kappa-chain gene, we synthesized cDNA from the mRNA of an anti-alpha(1----6)dextran hybridoma. The hybridoma had been produced using MPC-11 as the parental myeloma. Hybridization and sequence analysis of one clone showed that it was derived from a 1.2-kilobase (kb) kappa-chain mRNA that lacked a joining minigene segment (J). The mRNA had the leader region correctly spliced to the variable region (V) but, in the absence of a J, V kappa was flanked by 62 nucleotides (3202-3263) from the intervening sequence (between J5 and the kappa-chain constant region gene C kappa) before being spliced to C kappa. This mRNA originated from the kappa-chain-fragment gene of MPC-11 but differed from the previously described 0.8-kb kappa-chain-fragment mRNA [Choi, E., Kuehl, W.M. & Wall, R. (1980) Nature (London) 286, 776-779; Seidman, J.G. & Leder, P. (1980) Nature (London) 286, 779-783] in which the leader sequence is spliced directly to C kappa. This 1.2-kb mRNA was present as a polyadenylylated species in total cellular RNA but could not be detected in cytoplasmic RNA. Thus, it either failed to be transported out of the nucleus or was rapidly degraded in the cytoplasm. These studies show that transcripts of the kappa-chain-fragment gene are processed by two distinct splicing pathways to yield either a 0.8-kb mRNA with the leader region spliced directly to C kappa or a 1.2-kb mRNA with leader, V, 62 nucleotides of the intervening sequence, and C kappa.
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PMID:Alternative splicing patterns in an aberrantly rearranged immunoglobulin kappa-light-chain gene. 240 74

The monoclonality of myeloma proteins is usually demonstrated by their electrophoretic homogeneity and their reactivity with monovalent antisera directed against isotypic determinants of a single heavy chain and a single type of light chain. The absence of precipitation with anti-sera to immunoglobulin kappa and Lambda light chains is a constant character of heavy Chain Disease Proteins (HCDP). However, homogeneous M-components present in the sera of some patients and reacting only with anti-heavy-chain antisera were identified as IgA and IgD myeloma proteins bearing unreactive Lambda chains. In this study, the electrophoretic pattern of a patient serum showed a paraprotein with heterogeneous electrophoretic mobility and precipitation reaction limited to anti-IgD antiserum. The failure to react with anti-light chain antisera was observed by immuno-electrophoresis, immunofixation and rocket-immunoselection. Further analysis by crossed-immunoelectrophoresis revealed that IgD paraprotein contained two separate populations of molecules, one of them being retained when anti-Kappa and Lambda light chains anti-bodies were incorporated in the first dimension gel. It soon became obvious that the observed pattern was generated by enzymatic cleavage of native IgD myeloma protein.
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PMID:Spontaneous enzymatic cleavage of IgD myeloma protein giving a pattern of delta heavy chain disease. 251 42

The immunoglobulin kappa (kappa) gene promoter was activated by a "neutral" enhancer derived from Harvey murine sarcoma virus (HaMuSV) in immunoglobulin-producing myeloma cells, regardless of the enhancer's orientation or position in the vector. In one fibroblast line (3T3) the immunoglobulin kappa gene promoter was completely inactive when linked to the HaMuSV enhancer, whereas in mouse L cells, promoter activity was observed only with the HaMuSV enhancer in tandem with the immunoglobulin kappa gene promoter. The differential behavior of the gene promoter, when activated by a neutral enhancer in these three murine cell lines, suggests that promoter sequences contribute to the tissue-specific expression of this gene.
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PMID:Contribution of promoter to tissue-specific expression of the mouse immunoglobulin kappa gene. 299 13

Enhancers and promoters, cis-acting regulators of mammalian gene expression, are modular units containing multiple short binding sites for specific trans-acting transcription factors. To investigate if factors binding to enhancer sequences are functionally different from promoter-binding factors, we asked if a short DNA sequence element in the immunoglobulin kappa (kappa) light chain enhancer that binds to the nuclear factor NF-kappa B could also serve as a functional promoter element. A synthetic oligonucleotide containing this binding site was placed in either orientation upstream of the beta-globin TATA-element. In myeloma cells, the NF-kappa B binding site efficiently directed transcription. The promoter activity was directly correlated with the presence of the nuclear factor NF-kappa B: there was no transcription in fibroblasts or in unstimulated pre-B cells where the factor was absent. Transcription could be stimulated in pre-B cells by treatments known to activate NF-kappa B. Thus, the same nuclear factor can act as a positive activator of both enhancer and promoter function, suggesting that the two functions involve similar events in the transcription process.
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PMID:Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function. 314 Nov 47

Urine specimens from 164 patients sent to the laboratory for testing for Bence-Jones proteinuria were investigated using a new procedure. The protein in the untreated urine was subjected to isoelectric focussing in an agarose gel, transferred to a nitrocellulose membrane by blotting, and then stained by an immunoperoxidase technique for either immunoglobulin kappa or lambda chains. This technique was compared with a routine procedure for the detection of immunoglobulin light chains involving concentration by ultrafiltration, electrophoresis and then immunofixation. The new technique achieved a much increased rate of detection of Bence-Jones proteinuria. Among 51 patients known to have myeloma or macroglobulinaemia, Bence-Jones proteinuria was detected in 35 cases with the new procedure and in only 27 by the conventional method. In 28 patients with paraproteinaemia without other evidence of myeloma, macroglobulinaemia, leukaemia or lymphoma, 12 instances of Bence-Jones proteinuria were discovered with the new procedure, 10 of which were missed by the conventional method. The improved efficiency of detection is attributed to the high resolution of isoelectric focussing and the avoidance of protein loss from adsorption on to ultrafiltration membranes.
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PMID:Detection of Bence-Jones protein by isoelectric focussing of unconcentrated urine followed by nitrocellulose blotting and immunoperoxidase staining. 393 44


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