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)

Sera from 14 patients with an IgA M-component, six of whom had myelomatosis and eight with benign monoclonal gammopathy (BMG) were analysed. All six sera from patients with high IgA (greater than 40 g/l) and total protein (greater than 100 g/l) concentrations were hyperviscous (HV). Four of these six patients also had hyperviscosity syndrome (HVS). There was no correlation between the quantity of IgA dimers or polymers and the presentation of HV and HVS. The binding between IgA and albumin and alpha 1-anti-trypsin was not covalent. Differences in the microenvironment of S-S bonds or of aromatic amino acids between isolated monoclonal monomeric and dimeric IgA were demonstrated with circular dichroism. Besides that, differences in hydrophobicity (exposure of aromatic amino acids) between IgA from normal serum and monomeric and dimeric IgA from a myeloma serum were revealed using hydrophobic interaction chromatography. The significance of hydrophobic interactions involving IgA and the influence of such forces on the circulation of the molecules are discussed.
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PMID:Factors affecting IgA related hyperviscosity. 685 Dec 49

The proteinase from culture supernatants of Candida albicans strain CBS-2730 was purified virtually to homogeneity by ion-exchange chromatography and affinity chromatography. The enzyme consists of a single polypeptide chain with tryptophan at the N- and leucine at the C-terminus. Its molecular weight is approx. 45,000 and the isoelectric point is at pH 4.4. With albumin as a substrate an apparent Km was determined to be 7 . 10(-5) M. The enzyme is inhibited by pepstatin at equimolar ratio and thus is a carboxyl proteinase (EC 3.4.23.6). Other group-specific inhibitors, though, did not efficiently block the enzyme. Above pH 8.4 the enzyme undergoes alkaline denaturation which is accompanied by dimerization. The enzyme is a glycoprotein. It is stable in presence of non-ionic detergents and can be freeze-dried. The enzyme clots milk at pH 5.5 and has trypsinogen kinase activity. Among several purified proteins that have been tested as a substrate, only horse ferritin was resistant to proteolysis, while myeloma proteins of the A1- and A2-type were readily cleaved, as were two proteinase inhibitors of human serum. Antibodies against purified enzyme did not react with several commercial Candida antigen preparations; antibodies against the enzyme, though, have been detected repeatedly in sera from patients with manifest candidiasis.
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PMID:Properties of a purified proteinase from the yeast Candida albicans. 701 86

The development of the monoclonal antibody YC5/45 HLK (YC5/HLK) against a 5HT-bovine seroalbumin immunogen and its application for immunocytochemistry is described. The YC5/HLK antibody is the product of a rat x rat hybrid myeloma, producing a heavy chain and two light chains. In hemagglutination tests, the antibody cross-reacts to entirety with dopamine, serotonin, and tryptamine at high concentrations. The serotonin-albumin conjugate is 20,000 times more effective in displacing the binding antibody, while albumin itself goes unrecognized by the antibody. In fixed preparations of brain tissue, immunofluorescence is observed only in neurons known to contain serotonin, while no reaction is observed in dopamine-rich neurons. All immunofluorescence is extinguished by the use of agents that inhibit the biosynthesis of 5HT, but not of the catecholamines.
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PMID:Immunocytochemical detection of serotonin with monoclonal antibodies. 703 68

A recently developed gel-filtration technique allows protein-bound calcium fractions to be separated and quantitated; the protein is separated under physiological conditions of pH, temperature, and concentrations of Na, Mg, and Ca to assure that the calcium-proteinate equilibrium is not disturbed. We used this gel-filtration technique to study the protein-bound calcium fractions in 18 patients with hyperparathyroidism, multiple myeloma, diabetes, osteoporosis, or liver cirrhosis. We calculated the amount of calcium bound per gram of protein for each of the three protein peaks and the intrinsic association constant (Ka) for calcium/albumin. Results with the multiple myeloma patients (three IgG, one IgA) indicated that IgG did not bind calcium appreciably, that IgA had about the same affinity as albumin for Ca, and that Ka was slightly low for one patient of the IgG type (79 L/mol) and normal for the other three myeloma patients (106, 90, and 91 L/mol). Results for patients with the other diseases were also essentially normal, except for the osteoporesis patients (two men, one woman), whose Ka values (69, 75, and 73 L/mol) were lower than normal.
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PMID:Clinical studies of protein-bound calcium in various diseases. 707 38

Currently we are using two different ISO-DALT two-dimensional gel electrophoresis systems, designated MC-Iso 1 and MC-Iso 2, for the analysis of serum and plasma samples. Here we report quality-assurance data for both of these systems. CV values for the slopes of the pH gradient (ISO dimension) are 5.6% of less; CV values for the slopes of the molecular-mass curves (log Mr vs relative mobility in the DALT dimension) are 3.4% or less. We examined the various steps of the analysis in detail for reproducibility and protein loss, using radiolabeled albumin, alpha 2-macroglobulin, and beta 2-microglobulin. Generally, in the first dimension, less protein enters the MC-Iso 2 gels (our routine system in which silver stain is used) than enters the MC-Iso 1 gels (our wide-range system for myeloma serum samples, in which the gel is stained with Coomassie Blue), on the average, 87% as much. The CV at this stage for both systems is 5--8%. During equilibration, considerable amounts of protein are lost (approximately 30% in 10 min) from the ISO gel, and the reproducibility is also decreased. Resolution in the DALT dimension has, in most cases, little or no effect on either recovery or reproducibility. Overall, for most proteins expected to appear in an ISO gel of a given pH range, approximately 50--60% of the starting material may be expected to reside in the sodium dodecyl sulfate slab gel, under our conditions. The two most important variables affecting recovery are the concentration of the NaOH (used as catholyte) and the pH of the starting sample. The overall CV for the process is between 8 and 12%.
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PMID:Reproducibility and quality assurance of two-dimensional gel electrophoresis of serum specimens. 707 81

Three cortisol fractions, protein-unbound (U-F), transcortin-bound (Tr-F) and albumin-bound cortisol (Al-F) were measured in patients with dysproteinemia by a newly devised isocolloidosmolar equilibrium dialysis method. Total cortisol (Total-F) concentrations in patients with liver cirrhosis (LC), anorexia nervosa (AN) and cachexia due to cancer (CA) were higher than in normal subjects, and those in patients with nephrotic syndrome (NS) and multiple myeloma (MM) remained within the normal range. In all groups of patients, the U-F concentration, which is believed to be the sole active fraction of cortisol, showed significantly higher values than in the normal subjects. We, therefore attempted to find which of the two binding proteins contributes to the elevated U-F concentrations. Concentrations of each cortisol fraction are greatly changed by alterations in the Total-F concentration. We therefore compared the Tr-F against Total-F and Al-F, and U-F against Total-E of patients with those of normal subjects. It was found that decreased transcortin-binding and not albumin-binding in the patients with cirrhosis, nephrotic syndrome and myeloma contributed to an increase in the U-F concentration. Although decreased binding of albumin due to hypoalbuminemia was found in LC, NS, MM, CA and AN, it had relatively little effect on cortisol distribution in the serum.
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PMID:The serum concentrations of unbound, transcortin bound and albumin bound cortisol in patients with dysproteinemia. 718 82

The serum anion gap is often decreased in patients who have multiple myeloma or monoclonal gammopathy, presumably owing to the unmeasured contribution of cations by the paraprotein. In 83 patients who had moderate-to-severe diffuse (polyclonal) elevations in immunoglobulin concentration (> 3 g/dl), the mean serum anion gap was significantly lower than in patients who had normal concentrations of immunoglobulin. In the subgroup with immunoglobulin levels greater than 4 g/dl, the mean anion gap was 8.7 mEq/l, compared with 11.9 for the control group (P < 0.001). Known causes of decreased anion gap, such as hyperkalemia or hypercalcemia, were absent. The albumin concentration had a minimal effect on the anion gap. The mean anion gap was independent of the patient's diagnosis and the relative contribution of each immunoglobulin class to the total immunoglobulin. Thus, patients who have diffusely elevated immunoglobulin concentrations, as well as those who have monoclonal elevations, have a significantly lower mean anion gap. This low anion gap should be considered in the evaluation of the acid-base status of these patients.
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PMID:Anion gap and immunoglobulin concentration. 741 79

Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity.
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PMID:Effect of myeloma light chains on phosphate and glucose transport in renal proximal tubule cells. 753 8

Thirteen patients with light chain (LC) proteinuria (11 with multiple myeloma and two with monoclonal gammopathy of undetermined significance) were followed up for one to 3.5 (median 2.5) years and studied for urinary excretion of LCs, alpha 1-microglobulin (alpha 1 M), beta 2-microglobulin (beta 2M), albumin, and serum creatinine concentration at intervals of 6 +/- 2 months. At the beginning of the follow-up, urinary alpha 1M excretion correlated with that of beta 2M (r = 0.81, p = 0.0007) and LCs (0.69, p = 0.0084), and with the serum creatinine level (r = 0.56, p = 0.047). During the follow-up period, renal function remained stable in eight patients despite high or fluctuating LC excretion. In seven of them, urinary alpha 1M was repeatedly below 150 mg/24 h and in one it transiently exceeded that level. The remaining five patients had an unstable renal function (deterioration in four, improvement in one) although their urinary LC and albumin excretion during the study period was comparable to those in patients with stable renal function. In the five patients with unstable renal function, high (> 150 mg/24 h) urinary alpha 1M excretion was associated with a rise in the serum creatinine level. alpha 1M excretion was thus found to be a useful indicator of renal damage caused by LCs.
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PMID:Urinary alpha 1- and beta 2-microglobulin in light chain proteinuria. 755 29

Autologous transplantation after high-dose chemo or radiotherapy is now frequently used for the treatment of patients with multiple myeloma (MM). The collection of peripheral blood stem cells (PBSC) has a theoretical advantage over autologous bone marrow collection as the malignant plasmacytic contamination is believed to be lower. However, the extent of B cell contamination in PBSC has not been extensively investigated. Using an immunoglobulin heavy chain gene 'fingerprinting' technique at diagnosis and during apheresis after one cycle of chemotherapy we detected a monoclonal population in 44% of PBSC samples (9 positives in 22 studied). There was no correlation between contamination and sex, age, Durie and Salmon classification, C-reactive protein and albumin. A significant correlation was observed with beta 2 microglobulin serum level (P = 0.02). Twenty one patients were grafted and up to the present, with a mean follow-up of 12 months, 6 patients have relapsed including 4 patients with contaminating B cells. Our results suggest that PBSC contamination, defines a 'poor risk' group of patients, with poor prognosis. However, we could not exclude reinitiation of the disease by plasmacyte stem cells after grafting.
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PMID:Detection of malignant B cells in peripheral blood stem cell collections after chemotherapy in patients with multiple myeloma. 767 Mar 99


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