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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the accompanying paper (Friedman et al., Mol. Cell. Biol. 6:3791-3797, 1986), hepatoma-specific expression of the rat albumin promoter within the adenovirus genome was demonstrated. However, the rate of transcription was very low compared with that of the endogenous chromosomal albumin gene. Here we show that in hepatoma cells the adenovirus E1A enhancer, especially in the presence of E1A protein, greatly stimulates transcription from the albumin promoter but not the mouse beta-globin promoter. This enhancer-dependent stimulation did not occur in myeloma cells in which a virus containing a immunoglobulin promoter and enhancer did function. These experiments suggest a limited distribution in cultured differentiated cells of cell-specific transcription factors. However, either the regulation of such cell-specific factors breaks down in other cultured cells, or strictly cell-specific factors are not at play in controlling cell-specific transcription, because HeLa cells could transcribe the albumin promoter from the same start site about 10% as well as hepatomas could and 293 cells could transcribe both albumin and globin promoters.
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PMID:Cellular promoters incorporated into the adenovirus genome: effects of viral regulatory elements on transcription rates and cell specificity of albumin and beta-globin promoters. 294 9

Recombinant adenoviruses were constructed in which the viral E1A gene was deleted and the E1B promoter was replaced by the rat albumin, mouse beta-major globin, or mouse immunoglobulin heavy-chain promoter. After infection of human or rat hepatoma cells, E1B-containing mRNAs could be detected only from the virus containing the albumin promoter. Conversely, only the immunoglobulin promoter was active in virus-infected myeloma cells. However, in hepatoma cells transcription from the albumin promoter in the virus was much less than that of the endogenous cellular albumin gene or of other viral genes. In primary mouse hepatocytes endogenous albumin gene transcription was high immediately after plating but declined within 24 h. Expression of the albumin promoter in the virus paralleled that of the cellular albumin gene. From these results it appears that cell-specific expression of albumin depends on the presence of tissue-specific trans-acting factors, but the presence of such factors does not suffice for a maximal rate of transcription, a conclusion that requires direct comparison within a differentiated cell of a newly introduced and preexisting active cell gene.
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PMID:Cellular promoters incorporated into the adenovirus genome: cell specificity of albumin and immunoglobulin expression. 294 8

Both low urinary pH and radiocontrast agents may intensify myeloma nephrotoxicity. To study the effects of these factors, we determined inulin clearances (CIn) before and after infusions of human Bence Jones protein (BJP) in male Sprague-Dawley rats in a dose previously shown to be nephrotoxic. Rats that drank 0.15 M NaHCO3 for 48 hr before study had no change in CIn (+3 +/- 20%) after BJP unlike those that drank 0.15 M NH4Cl (-33 +/- 14%, P less than 0.05); urinary pH differed (7.6 +/- 0.1 vs. 6.2 +/- 0.1, P less than 0.05), but urinary flow rates did not. The acidifying regimen was used in all subsequent groups. Infusion of diatrizoate (DTZ) after BJP produced a further decrease in CIn (-85 +/- 8%, P less than 0.05). In contrast, infusion of albumin, which raised plasma protein concentration to that seen in BJP-infused rats, did not change CIn (+39 +/- 17%). Infusion of beta-lactoglobulin also led to a greater decrease in CIn after DTZ (-35 +/- 9 vs. -67 +/- 8%, P less than 0.05), but myoglobin did not (-58 +/- 7 vs. -54 +/- 12%). Urinary pH and flow rate did not differ between any DTZ-infused group and its appropriate control. These data suggest that aciduria independent of urinary flow rate increases the nephrotoxicity of BJP. In this setting, DTZ further intensifies the nephrotoxicity of BJP as well as some but not all filterable proteins.
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PMID:Effect of urinary pH and diatrizoate on Bence Jones protein nephrotoxicity in the rat. 298 52

Concanavalin A binding to glycoprotein bands on nitrocellulose blots was used to detect mannose, sorbose, N-acetylgalactosamine and/or glucose residues on 100% (31/31) of human Bence Jones protein light chains, following sodium dodecyl sulphate-polyacrylamide gel electrophoresis. All (20/20) light chains form IgG myeloma proteins and light chains from a preparation of normal polyclonal human IgG were also bound by concanavalin A. The specificity of concanavalin A for glycoproteins was demonstrated by its binding to human Fc fragments and a human monoclonal anti-Rhesus D antibody (REG-A), but not to human albumin pFc' fragments and aglycosylated REG-A derived from cells grown in the presence of the glycosylation inhibitor tunicamycin. These results suggest that all Bence Jones proteins and light chains from myeloma IgG proteins contain mono- or oligosaccharides linked O-glycosidically to serine or threonine residues.
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PMID:Immunogenicity and antigenicity of immunoglobulins: detection of human immunoglobulin light-chain carbohydrate, using concanavalin A. 311 95

A 74-year-old man presented with interstitial pulmonary disease which was proven to be alveolar septal amyloidosis by transbronchial biopsy. Multiple myeloma was diagnosed on the basis of monoclonal IgG-lambda protein in serum, monoclonal lambda light chains in urine, a bone marrow plasmacytosis of 22 percent, and serum IgA and IgM levels less than 100 mg/dl and 50 mg/dl, respectively. Appropriate investigations failed to show additional sites of deposition of amyloid. Analysis of fluid from bronchoalveolar lavage showed an increase in total cells recovered, a lymphocytosis with a ratio of T helper over T suppressor cells greater than that in peripheral blood, the presence of an IgG-lambda paraprotein, and an IgG/albumin ratio greater than that in serum. While plasma cells could not be identified in the recovered cell population, cultured cells from bronchoalveolar lavage fluid showed increased production of IgG. These findings provide evidence of an ongoing pulmonary immune response resulting in excess IgG-lambda protein in the pulmonary compartment, a factor which may contribute to the development of amyloidosis.
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PMID:Pulmonary immunologic features of alveolar septal amyloidosis associated with multiple myeloma. 311 88

The Coomassie Brilliant Blue G-250 method for urinary proteins underestimates urinary immunoglobulin light chains when albumin or pooled serum is used as the protein standard. The specific color yields of these and other proteins can be brought closer together by adding sodium dodecyl sulfate to the reagent; however, there is some loss of sensitivity. We found such a reagent to be satisfactory for assaying urinary proteins on studying 43 patients with light-chain proteinuria, 19 of whom had multiple myeloma and six possible multiple myeloma.
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PMID:Improved measurement of urinary total protein (including light-chain proteins) with a Coomassie brilliant blue G-250-sodium dodecyl sulfate reagent. 311 57

To investigate the direct toxicity of human Bence Jones protein (BJP), individual nephrons of male Sprague-Dawley rats were perfused in vivo at 20 nl/min with an artificial tubule fluid (ATF) that contained no protein, a human kappa BJP (5 g/dl), or bovine serum albumin (5 g/dl), and proximal convoluted tubule function and morphology were examined. Perfusion with BJP perfusate for less than or equal to 5 minutes produced no changes (P = NS) in absorption of water, Jv, (1.09 +/- 0.20 vs. 1.50 +/- 0.25 nl/min/mm), chloride, JCl, (95 +/- 47 vs. 123 +/- 41 pEq/min/mm), and glucose, JG, (39 +/- 3 vs. 40 +/- 5 pmol/min/mm) compared to perfusions with only ATF. However, perfusion for at least 20 minutes with the same BJP perfusate produced decreased (P less than 0.025) in Jv (0.58 +/- 0.12 vs. 1.15 +/- 0.14 nl/min/mm) and JG (27 +/- 3 vs. 38 +/- 3 pmol/min/mm) compared to perfusions with ATF alone; the decrease in JCl (64 +/- 47 vs. 119 +/- 27 pEq/min/mm) did not reach statistical significance. Perfusion for 20 minutes with ATF containing albumin resulted in no changes in Jv (1.22 +/- 0.21 vs. 1.15 +/- 0.14 nl/min/mm), JCl (207 +/- 29 vs. 119 +/- 27 pEq/min/mm), and JG (31 +/- 1 vs. 38 +/- 3 pmol/min/mm), when compared to the ATF perfusions. Immunocytochemistry, immunofluorescence and immunoelectron microscopy of the BJP-perfused tubules demonstrated the kappa light-chain protein in endosomes and activated lysosomes. In addition, cellular desquamation and fragmentation, prominent cytoplasmic vacuolation, and focal loss of the microvillus border were found in the BJP-perfused tubules, but not in the albumin-perfused tubules. In conclusion, these functional and morphologic data show that a human kappa light-chain is toxic to the proximal convoluted tubule of the rat. This toxicity occurred in a time-dependent fashion when the lysosomal system was markedly activated. Direct damage of the tubule epithelium by BJP's may be involved in the development of the tubulointerstitial nephropathy associated with multiple myeloma.
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PMID:Human Bence Jones protein toxicity in rat proximal tubule epithelium in vivo. 312 60

We have prepared 16 anti-bilirubin monoclonal antibodies and described their unique reactivity to bilirubin and related compounds. Using the modified mixed anhydride method, bilirubin was covalently coupled to bovine serum albumin. We performed somatic cell fusion between murine spleen cells immunized with this bilirubin-albumin complex and murine myeloma P3-X63-Ag8-U1 cells. After screening assays, 16 clones were identified which were producing antibodies not to albumin but to haptenic bilirubin. In inhibition analysis, the antibodies in the culture supernatants cross-reacted with bilirubin glucuronides to varying degrees, but rarely reacted with structurally related biliverdin, hemin, and azodipyrroles of bilirubin. Albumin, when present in the solution, much reduced the reactivity of several monoclonal antibodies to unconjugated bilirubin, and this effect was partly reversed by addition of salicylate which dissociates the binding between bilirubin and albumin.
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PMID:Anti-bilirubin monoclonal antibody. I. Preparation and properties of monoclonal antibodies to covalently coupled bilirubin-albumin. 319 Nov 53

The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum beta 2-microglobulin (S-beta 2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S-TK), serum lactate dehydrogenase (S-LDH), S-creatinine, haemoglobin (Hb), ESR, S-albumin, age and clinical stage were also significant. No such relationship was found with M-component, presence of light chains in urine, type of secreted immunoglobulin or S-calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S-beta 2m, age and S-TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above. Individual analysis of the variables showed that Hb had the most significant relation to effect of initial therapy. Other significant variables were S-TK, S-beta 2m and age. When using the multivariate approach, Hb alone was found to contain all the relevant information.
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PMID:Biochemical markers in multiple myeloma: a multivariate analysis. 328 7

This paper critically examines the usefulness of serum albumin measurement in the light of current laboratory practice and knowledge of the pathophysiology of albumin metabolism. The main conclusions and recommendations are as follows: (i) Albumin measurement forms a limited, but useful part of the investigation of liver disease; a normal serum albumin concentration makes the diagnosis of cirrhosis unlikely, while a low level in viral hepatitis suggests either severe hepatocellular damage or other complications. (ii) Albumin measurement is essential in selecting patients for, and in determining the amount and frequency of, albumin replacement. (iii) Serum albumin concentration provides a useful indication of prognosis in myeloma. (iv) In the long-term management of patients undergoing enteral or parenteral nutrition, serum albumin concentration is one of several parameters which, together, are useful in predicting the outcome of treatment. (v) The serum albumin concentration may provide a clue to the aetiology of unexplained oedema. (vi) Serum albumin measurement is useful in indicating the level of ionised calcium and of unbound unconjugated bilirubin.
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PMID:When is serum albumin worth measuring? 332 60


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