Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the development of severe hypophosphatemia and urinary phosphate wasting in two patients with multiple myeloma. In both cases, the serum phosphorus was repeatedly less than 1.0 mg/dL despite vigorous replacement, and the calculated fractional excretion of urinary phosphorus was greater than 100%. Neither patient demonstrated other tubular defects typical of Fanconi's syndrome. With treatment of the myeloma, both patients achieved normalization of the serum phosphorus and no longer required phosphorus supplementation. We believe that multiple myeloma should be considered in the differential diagnosis in patients with profound hypophosphatemia, urinary phosphate wasting, and otherwise intact tubular function.
 ...
PMID:Profound hypophosphatemia and isolated hyperphosphaturia in two cases of multiple myeloma. 904 Dec 22

Growth of the murine B-lymphocyte cell line CC9C10 and the myeloma SP2/0 was enhanced significantly by the presence of the unsaturated fatty acids, oleic and linoleic acids in serum-free culture. The cellular content of linoleic and oleic acids gradually increased during continuous culture passage, with no evidence of regulatory control. Over 10 culture passages in the presence of these fatty acids, the unsaturated/saturated fatty acid ratio of all cellular lipid fractions increased substantially. Most of the fatty acid accumulated in the polar lipid fraction (more than 74%) and only a small proportion was oxidized to CO2 (0.5%). Linoleic acid caused a decrease to one-eighth in the rate of metabolism of glutamine and a 1.4-fold increase in the rate of metabolism of glucose. There was no change in the relative flux of glucose through the pathways of glycolysis, pentose phosphate or the tricarboxylic acid cycle. The changes in energy metabolism were reversed when the cells were removed from fatty acid-supplemented medium. The most plausible explanation for these effects is the observed decrease in the rate of uptake of glutamine into cells loaded with linoleic acid. Growth of the CC9C10 cells in linoleic acid caused the Km of glutamine uptake to increase from 2.7 to 23 mM, whereas glucose uptake was unaffected.
 ...
PMID:Unsaturated fatty acids enhance cell yields and perturb the energy metabolism of an antibody-secreting hybridoma. 906 85

EctoATPases are extracellular membrane-bound enzymes that catalyze the hydrolysis of the gamma phosphate from ATP. EctoATPase is expressed by activated and immortalized Epstein-Barr virus-transformed human peripheral blood B lymphocytes and murine B cell hybridomas. By contrast, ectoATPase activity is not expressed on nontransformed human peripheral blood B lymphocytes, murine spleen cells, or murine myeloma cells. The K(m) for ATP for the B cell ectoATPases ranged from 5 to 77 microM; the Vmax ranged from 48 to 129 pmol/ min/10(4) cells. The enzyme required Mg2+ for maximal activity with little dependence on Ca2+. ADP and purine and pyrimidine nucleoside triphosphates were competitive inhibitors of the catalytic reaction. A putative ectoATPase protein has been identified by Western blot analysis of membrane proteins from the immortalized B cells. Under reducing conditions, antiectoATPase antibodies cross-reacted with a 66-kDa protein from murine B cell hybridoma membranes. By contrast a 200-kDa protein from the B cell hybridoma membranes cross-reacted with the antibodies under nonreducing conditions, suggesting a disulfide-linked trimer. The antibodies also cross-reacted with a 66-kDa protein from human B cell membranes under reducing conditions, but did not cross-react with membrane proteins under nonreducing conditions. This suggests that the antibody epitope(s) recognized on the reduced human protein is masked under nonreducing conditions. Thus, this work demonstrates: (1) that ectoATPase may serve as a marker for B cell activation; and (2) mammalian and avian ectoATPases have conserved interspecies immunological epitopes and kinetic properties.
 ...
PMID:Identification and partial characterization of ectoATPase expressed by immortalized B lymphocytes. 912 71

We report a patient with multiple myeloma and a prolonged history of hypophosphatemia who had remained asymptomatic. Extensive evaluation for a cause, including the search for a renal tubular disorder, oncogenous osteomalacia, or a parathyroid hormone (PTH)-related protein was unproductive. Renal biopsy showed no evidence of myeloma kidney. Subsequent mixing of the immunoglobulin G (IgG) fraction from the patient's serum with normal human serum, confirmed that the observed hypophosphatemia was spurious, resulting from interference of large amounts of an abnormal IgG with a standard automated laboratory assay for phosphate.
 ...
PMID:Spurious hypophosphatemia in a patient with multiple myeloma. 932 75

In December 1995, ambient radon levels exceeding 10,000 Bq/m3 were measured in a basement shelter workroom of a multilevel East Talpiot, Jerusalem, public elementary school (six grades, 600 students). The measurements were taken after cancers (breast and multiple myeloma) were diagnosed in two workers who spent their workdays in basement rooms. The school was located on a hill that geologic maps show to be rich in phosphate deposits, which are a recognized source for radon gas and its daughter products. Levels exceeding 1000,000 Bq/m3 were measured at the mouth of a pipe in the basement shelter workroom, the major point of radon entry. The school was closed and charcoal and electret ion chamber detectors were used to carry out repeated 5-day measurements in all rooms in the multilevel building over a period of several months. Radon concentrations were generally higher in rooms in the four levels of the building that were below ground level. There were some ground-level rooms in the building in which levels reached up to 1300 Bq/m3. In rooms above ground level, however, peak levels did not exceed 300 Bq/m3. Exposure control based on sealing and positive pressure ventilation was inadequate. These findings suggested that radon diffused from highly contaminated basement and ground-floor rooms to other areas of the building and that sealing off the source may have led to reaccumulation of radon beneath the building. Later, subslab venting of below-ground radon pockets to the outside air was followed by more sustained reductions in indoor radon levels to levels below 75 Bq/m3. Even so, radon accumulated in certain rooms when the building was closed. This sentinel episode called attention to the need for a national radon policy requiring threshold exposure levels for response and control. A uniform nationwide standard for school buildings below 75 Bq/m3 level was suggested after considering prudent avoidance, the controversies over risk assessment of prolonged low-level exposures in children, and the fact that exposures in most locations in the Talpiot school could be reduced below this level. Proposal of this stringent standard stimulated the search for a strategy of risk control and management based on control at the source. This strategy was more effective and probably more cost effective than one based on suppression of exposure based on sealing and ventilation. Because many Israeli areas and much of the West Bank area of the Palestinian National Authority sit on the same phosphate deposits, regional joint projects for surveillance and control may be indicated.
 ...
PMID:Radon exposures in a Jerusalem public school. 946 53

As part of the development of structured models for the metabolism of myeloma cells in suspension culture, a study was made of the subcellular localization of key enzymes of glucose and glutamine metabolism. Steady state chemostat cultures of the mouse myeloma SP2/0-Ag14 were used as a reproducible source of biomass. Homogenates of the cells, obtained via mechanical disruption, were separated into a mitochondrial and a cytosolic fraction via differential centrifugation. The following conclusions are drawn: (1) approximately one fifth of the hexokinase activity of cell-free homogenates is associated with the mitochondria; (2) a malate-aspartate shuttle may operate for oxidation of cytosolic NADH, as indicated by high levels of malate dehydrogenase and aspartate aminotransferase in both particulate and soluble fractions; (3) the pentose phosphate pathway and isocitrate dehydrogenase may contribute to the provision of cytosolic NADPH; (4) phosphoenolpyruvate carboxykinase and pyruvate kinase, which are present in high activities, are exclusively cytosolic and probably play a key role in glutamine metabolism; (5) oxidation of glutamine via these enzymes leads to the formation of pyruvate that enters the same pool as pyruvate generated by glycolysis. As a result, lactate and alanine formation can occur from both glucose and glutamine.
 ...
PMID:Subcellular localization of enzyme activities in chemostat-grown murine myeloma cells. 965 Feb 85

Mutations of the gene encoding the tumor suppressor protein p53 are the most common molecular alterations of cancer cells found in about half of all human tumors. Mutations which cluster in well-defined hot spots change the structure of the protein thus affecting its ability to bind to DNA. Post-translational modifications, primarily phosphorylation, might also influence how p53 binds to DNA or folds to its active tetrameric form. However, the lack of appropriate biochemical markers to characterize the status of phosphorylation in different cell types and in cells at different stages of tumor progression has prohibited such investigations. To generate a sensitive and phosphorylation-specific monoclonal antibody (mAb), we chemically synthesized the C-terminal 23 amino acid stretch of human p53 in a double-phosphorylated form. The peptide 371-393, carrying phosphate groups on Ser378 and Ser392, was co-synthesized with a turn-inducing spacer and peptide 31D, an immunodominant T-helper cell epitope in mice of the H-2k haplotype. After immunization and fusion of splenocytes with myeloma cells, a number of mAbs were obtained, from which mAb p53-18 emerged as a highly sensitive reagent. By enzyme-linked immunosorbent assay, p53-18, a mAb of the IgM isotype, recognized phosphorylated p53, expressed in insect cells infected with a recombinant baculovirus but not p53 expressed in Escherichia coli. Moreover, murine p53 from insect cells could be immune purified with mAb p53-18. Mass spectrometry following tryptic digestion of the purified protein and liquid chromatography of the fragments verified the presence of phosphate groups at both Ser375 and Ser389. From the corresponding human protein fragments, mAb p53-18 bound to the immunizing peptide phosphorylated on Ser378 and on Ser392, but failed to cross-react with the unphosphorylated peptide, or peptides phosphorylated individually on either Ser378 or Ser392. The binding to the unphosphorylated peptide could be restored, however, if the peptide conformation was stabilized to that of an alpha-helix. The immunogenic nature of the multiphosphorylated C-terminus of p53 is indicated by the finding that human sera, mostly from cancer patients, preferentially recognized the double-phosphorylated peptide over the monophosphorylated or unphosphorylated analogs. Antibody p53-18 appears to be a highly useful biochemical marker to detect low levels of p53 protein in different tissues, and to be a key tool to characterize the phosphorylation status of the C-terminus of p53 protein originated from various sources.
 ...
PMID:A monoclonal antibody to a multiphosphorylated, conformational epitope at the carboxy-terminus of p53. 973 74

The enzyme that catalyzes the formation of GDP-L-fucose from GTP and beta-L-fucose-1-phosphate (i.e. GDP-beta-L-fucose pyrophosphorylase, GFPP) was purified about 560-fold from the cytosolic fraction of pig kidney. At this stage, there were still a number of protein bands on SDS gels, but only the 61-kDa band became specifically labeled with the photoaffinity substrate, azido-GDP-L-[32P]fucose. Several peptides from this 61-kDa band were sequenced and these sequences were used for cloning the gene. The cDNA clone yielded high levels of GFPP activity when expressed in myeloma cells and in a baculovirus system, demonstrating that the 61-kDa band is the authentic GFPP. The porcine tissue with highest specific activity for GFPP was kidney, with lung, liver, and pancreas being somewhat lower. GFPP was also found in Chinese hamster ovary, but not Madin-Darby canine kidney cells. Northern analysis showed the mRNA in human spleen, prostate, testis, ovary, small intestine, and colon. GFPP was stable at 4 (o)C in buffer containing 50 mM sucrose, with little loss of activity over a 9-day period. GTP was the best nucleoside triphosphate substrate but significant activity was also observed with ITP and to a lesser extent with ATP. The enzyme was reasonably specific for beta-L-fucose-1-P, but could also utilize alpha-D-arabinose-1-P to produce GDP-alpha-D-arabinose. The product of the reaction with GTP and alpha-L-fucose-1-P was characterized as GDP-beta-L-fucose by a variety of chemical and chromatographic methods.
 ...
PMID:GDP-L-fucose pyrophosphorylase. Purification, cDNA cloning, and properties of the enzyme. 980 72

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P < .01). The tumor regression also results in protective immunity against a second challenge with parental tumor cells, which is mainly mediated by VKCK tumor-specific CD8+ T cells. These results indicate that AdV-mediated cytokine gene therapy may be a useful approach in the clinical management of solid human tumors.
 ...
PMID:Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression. 991 92

Activities of enzymes in glycolysis, the pentose phosphate pathway, the tricarboxylic acid cycle, and glutaminolysis have been determined in the mouse myeloma SP2/0.Ag14. Cells were grown on IMDM medium with 5% serum in steady-state chemostat culture at a fixed dilution rate of 0.03 h-1. Three culture conditions, which differed in supply of glucose and oxygen, were chosen so as to change catabolic fluxes in the central metabolism, while keeping anabolic fluxes constant. In the three steady-state situations, the ratio between specific rates of glucose and glutamine consumption differed by more than twentyfold. The specific rates of glucose consumption and lactate production were highest at low oxygen supply, whereas the specific rate of glutamine consumption was highest in the culture fed with low amounts of glucose. Under low oxygen conditions, the specific production of ammonia increased and the consumption pattern of amino acids showed large changes compared with the other two cultures. For the three steady states, activities of key enzymes in glycolysis, the pentose phosphate pathway, glutaminolysis, and the TCA cycle were measured. The differences in the in vivo fluxes were only partially reflected in changes in enzyme levels. The largest differences were observed in the levels of glycolytic enzymes, which were elevated under conditions of low oxygen supply. High activities of phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32) in all cultures suggest an important role for this enzyme as a link between glutaminolysis and glycolysis. For all enzymes, in vitro activities were found that could accommodate the estimated maximum in vivo fluxes. These results show that the regulation of fluxes in central metabolism of mammalian cells occurs mainly through modulation of enzyme activity and, to a much lesser extent, by enzyme synthesis.
 ...
PMID:Fluxes and enzyme activities in central metabolism of myeloma cells grown in chemostat culture. 1009 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>