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 authors report a case of a gastric involvement by a multiple myeloma, suspected on ultrasonography although the gastric endoscopy was normal. The barium examination and the CT scan agreed with the ultrasound hypothesis confirmed by histology.
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PMID:[Kahler's disease of the stomach. A case report]. 229 Jan 46

Enhancer activity of the rabbit immunoglobulin kappa light chain gene intron conserved region (KICR) was examined in mouse myeloma cells using transient expression experiments. Compared to the homologous region of the mouse kappa light chain gene, the rabbit KICR shows nearly no stimulatory effect on expression of the indicator gene, cat. Experiments with mouse-rabbit chimeric KICRs indicated that differences in the region around the NF-kappa B binding site are responsible for the impaired activity of the rabbit KICR whereas mouse sequences covering the kappa E2 and kappa E3 motifs can be replaced by the equivalent rabbit fragment without affecting enhancer function. Creation of a perfect mouse NF-kappa B target sequence in the rabbit gene only partially restores enhancer activity. Furthermore, mouse and rabbit DNA fragments encompassing the NF-kappa B target sequence behave in an identical manner in an electrophoretic mobility shift assay. The results indicate species-related functional differences in the immunoglobulin kappa light chain gene enhancer and suggest that although the NF-kappa B binding site plays a crucial role in enhancer activity surrounding gene elements are also necessary for full enhancer effect.
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PMID:Determinant differences between the rabbit and mouse immunoglobulin kappa enhancers impair the activity of the rabbit enhancer in mouse myeloma cells. 250 61

A 73-year-old woman with metastatic transitional cell carcinoma of the bladder developed vaginal bleeding a few days after undergoing radical cystectomy. She had no other signs of mucocutaneous bleeding. Coagulation studies revealed a markedly prolonged thrombin time (greater than 600 seconds), a slightly prolonged reptilase time (20 seconds), and mildly elevated fibrinogen (4.39 g/L), and fibrin D-dimer (200 to 500 ng/mL) levels. Treatment of the patient's plasma in vitro with protamine or barium sulfate normalized the thrombin time. The anticoagulant activity corresponded to 0.15 heparin U/mL when measured by a thrombin time assay using normal plasma as substrate and standardized with porcine heparin. The anticoagulant was quantitatively bound to and subsequently eluted with 1 mol/L NaCl from quaternary aminoethyl (QAE) Sephadex, and then isolated by affinity chromatography on immobilized antithrombin III. The isolated anticoagulant was shown to be sensitive to heparinase digestion. Therefore, the inhibitor has functional and chemical properties similar to those of high-affinity heparin. Thus far, this is the only anticoagulant of this type isolated from the plasma of a patient bearing a tumor other than plasma cell myeloma.
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PMID:Isolation of a heparin-like anticoagulant from the plasma of a patient with metastatic bladder carcinoma. 275 13

The adenovirus E1b region codes for two major tumor antigens of 19 kD and 55 kD, which are important for cell transformation. Our results indicate that the 19-kD T antigen possesses two enhancer-regulatory functions. It can trans-activate enhancer-linked promoters and relieve enhancer repression mediated by viral and cellular repressors. The 19-kD activation function enhances expression from different promoters linked to SV40, Py, Ela, and immunoglobulin heavy-chain enhancers. Enhancer activation by the 19-kD protein appears to be cell type-specific, since the heavy-chain and SV40 enhancers were not trans-activated in myeloma cells whereas the same enhancers were trans-activated in fibroblasts. The 19-kD enhancer activation function appears to be dominant over the enhancer repression function of E1a, since in cells expressing the 19-kD protein there is no significant repression despite a large increase in E1a expression. The 19-kD T antigen activates the Py enhancer in undifferentiated F9 cells indicating that the activation function of E1b masks enhancer repression by an "E1a-like" cellular gene product. The enhancer activation function of the 19-kD T antigen may be important for cell transformation and cell differentiation.
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PMID:Adenovirus transforming 19-kD T antigen has an enhancer-dependent trans-activation function and relieves enhancer repression mediated by viral and cellular genes. 296 99

In an attempt to understand the relationship of amino acid sequence to the formation of primary or multiple myeloma-related amyloid (AL amyloid), we have determined the complete amino acid sequence of amyloid protein BAN. This protein belongs to the kappa I immunoglobulin light chain subgroup and has a polypeptide chain length of 126 amino acids. It encompasses the entire variable region, the joining segment and the first tryptic peptide of the constant region. This protein has two unique features. First, the molecule is glycosylated. At position 61 the usual arginine residue has been replaced by an asparagine with the generation of the signal sequence Asn-Phe-Thr, to which a glucosamine-containing carbohydrate unit is attached. Secondly, the protein is not monoclonal but consists of two chains which have the same variable region but different J-segments. Comparison of the BAN sequence with other amyloid and nonamyloid kappa I proteins reveals a systematic difference between the two groups. In the amyloid proteins, several hydrophilic framework residues have been replaced by hydrophobic residues. These substitutions may provide the nucleation sites for self-aggregation and fibril formation.
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PMID:Polymorphism in a kappa I primary (AL) amyloid protein (BAN). 308 40

Spleen cells obtained from mice immunized with partially purified human coagulation Factor V were fused with NS-1 mouse myeloma cells, and hybrids were selected. Culture media were screened for anti-Factor V activity, and an antibody-positive clone was obtained and passaged as an ascites tumor in mice. The ascitic fluid from the hybridoma-bearing mouse could be diluted 1:10(6) before losing reactivity in an anti-Factor V radioimmunoassay. When immobilized on agarose, the monoclonal antibody quantitatively removed Factor V activity from human plasma. Factor V activity could be eluted with 1.2 M NaCl at pH 6.5. Homogeneous Factor V was isolated by chromatography of barium citrate-adsorbed, polyethylene glycol 6000 precipitated plasma on the antibody column followed by chromatography on phenyl-Sepharose. The isolated Factor V exhibited a single band upon gel electrophoresis in sodium dodecyl sulfate with an apparent Mr comparable to that of bovine Factor V (330,000). Upon exposure to thrombin, the activity of Factor V increased 53-fold when measured in Factor V-deficient plasma. This increased activity was associated with discrete proteolytic cleavages of the parent molecule.
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PMID:Isolation of functional human coagulation factor V by using a hybridoma antibody. 694 Dec 42

Our patient, who was known to have multiple myeloma, presented with weight loss, rectal bleeding, and a barium enema study suggestive of a colitis with a mass lesion. Colonoscopy with biopsy revealed the mass to be large mucosal folds infiltrated with amyloidosis. Amyloidosis has been reported to mimick malignancy, mainly by tumorous deposits in the stomach and less commonly in the small and large bowels. Gastrointestinal surgery in patients with amyloidosis potentially may have undesirable consequences due to failure of anastomotic suture lines and subsequent sepsis (6, 11, 17, 18). The knowledge that amyloidosis may be associated with multiple myeloma and an appreciation of the wide range of gastrointestinal roentgenographic findings in patients with amyloidosis should prompt the clinician to obtain endoscopic and biopsy evaluation of these patients.
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PMID:Amyloidosis masquerading as inflammatory bowel disease with a mass lesion simulating a malignancy. 708 Nov 72

The lambda 5 protein is expressed in pre-B cells in association with VpreB and mu-heavy chains, and is critical for differentiation to the B cell stage. Pre-B cell-specific expression of the lambda 5 and VpreB genes is regulated at the level of transcription initiation. In this report, we have identified several DNase l-hypersensitive sites 2.5- to 6.0-kb downstream of the lambda 5 gene, which are present in the pre-B cell line 70Z/3, but not in the myeloma cell line j558L. These sites, however, were shown to have no transcriptional enhancer activity as measured by transient transfection. Enhancer activity was identified within a 361-bp fragment (-296 to +65, where +1 is the major 5' transcription initiation site) upstream of the mouse lambda 5 gene. This activity is orientation and position independent, and is also tissue and differentiation stage specific (active in pre-B but not B and T cells). Deletion constructs indicate that three adjacent areas (-210 to -169, -153 to -64, and -64 to -22) are all necessary for enhancer activity. Pre-B cell-specific promoter activity was shown to reside within the -219 to +109 fragment. Basal promoter activity resides within the -64 to +109 fragment, but is not tissue specific or stage specific. A negative element within the -101 to -64 region is active in all lymphoid cell lines tested and therefore cannot by itself be responsible for the tissue and stage specificity. The data indicate that the elements responsible for the enhancer activity (-210 to -22) are part of the lambda 5 gene promoter and likely confer the tissue and stage specificity via positive elements within the -210 to -22 region.
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PMID:Identification and localization of a developmental stage-specific promoter activity from the murine lambda 5 gene. 765 Mar 80

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

Notch is a transmembrane protein involved in cell fate determination. In the present study, we observed temporally and spatially restricted expression of Notch1 in developing cartilage. Notch1 was localized starting from the mesenchymal condensation stage of embryonic mouse forelimbs. Interestingly, although localization could not be detected in the proliferating chondrocytes, obvious immunoreactivity indicating its expression was retained in the perichondrial region. Next, we investigated the expression of Notch1 and related molecules in a chondrogenic cell line, ATDC5 cells. Notch1, Delta-like (Dll)1, Deltex2, and Deltex3 were coexpressed after 6-day insulin treatment. Expression of Hairy and Enhancer of split homologue (HES)-1 followed thereafter. These results suggest that Notch may have a role in the early stage of chondrogenesis. To assess the effect of Notch activation, we cultured ATDC5 cells with a myeloma clone constitutively expressing Dll1, a ligand of Notch. We also used an adenovirus vector to express the constitutively active Notch1 intracellular domain (NIC). Activating either the endogenous or exogenous Notch receptor dramatically inhibited chondrogenic cell differentiation of ATDC5 cells, as assessed by Alcian blue staining of the cells and chondrocyte differentiation markers. Last, we investigated the effect of NIC on the proliferation of the ATDC5 cells. Expression of NIC by the adenovirus strongly suppressed thymidine incorporation. These results indicate that Notch is expressed in the initial stage of chondrogenic cell differentiation and has a strong inhibitory effect on both differentiation and proliferation of the cells when activated. The expression of Notch decreases as chondrogenic differentiation proceeds; however, a population of the cells with sustained expression of Notch1 become perichondrial cells. Considering that the perichondrium acts as a stem cell source of osteoblasts and chondrocytes, Notch1 may have a role in the formation of these cells by suppressing both differentiation and proliferation.
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PMID:Suppression of differentiation and proliferation of early chondrogenic cells by Notch. 1458 90


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