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)

Mouse myeloma immunoglobulin IgM heavy chains were cleaved with cyanogen bromide into nine peptide fragments, four of which contain asparagine-linked sites of glycosylation. Three of these glycopeptides contain a single site located at asparagines 171, 403, and 563 in the sequence of the intact heavy chain. Another glycopeptide contains two sites of glycosylation at asparagines 332 and 364. All sites contain multiple oligosaccharide structures with a trend towards increased processing from the COOH to the NH2 terminus. Structures present at asparagine 563, located only exclusively high mannose oligosaccharides. Asparagine 403, located penultimate to the COOH terminus, has a major component that is of a complex nature but is incompletely processed. Other sites contain predominantly complex structures consisting of biantennary or triantennary branches. The unusual structure found at asparagine 403 contains fucose even though only one branch has been processed to a terminal galactose. These studies suggest that each site has a unique set of heterogeneous oligosaccharides derived from a complex processing system which utilizes a combination of "position completeness" and polypeptide structure to determine final carbohydrate structure.
 ...
PMID:Heterogeneity of asparagine-linked oligosaccharides of five glycosylation sites on immunoglobulin M heavy chain from mineral oil plasmacytoma 104E. 681

The crystallizable myeloma immunoglobulin IgG1 KOL [allotype Gm(-1,4), (gamma 1, gamma)2] which is well characterized in its three-dimensional structure by X-ray diffraction analysis of high resolution has been proved to be homogenous by polyacrylamide gel electrophoresis. The H- and L-chains were separated by gel filtration after complete reduction and carboxymethylation and were characterized by amino acid analysis, end group determination and polyacrylamide gel electrophoresis, respectively. The intact IgG1 KOL was cleaved by cyanogen bromide and all CNBr-fragments were isolated and characterized. The reduced and carboxymethylated H-chain was digested by trypsin and the tryptic hydrolysate was separated by ion-exchange chromatography. Using different procedures of rechromatography 35 out of 37 tryptic H-chain peptides could be isolated in sufficient amounts, the missing 2 peptides were produced by tryptic digestion of 2 CNBr-fragments. The amino acid sequences of all tryptic peptides were determined using a modified Edman degradation method after separation of the enzymatic cleavage products by high-performance liquid chromatography (HPLC). The complete primary structure of the VH-part of the H-chain was established by isolation and partial sequence determination of overlapping peptides obtained from cleavage of the intact H-chain by Staphylococcus aureus proteinase. The gamma 1-H-chain KOL comprises 455 amino acid residues and belongs to subgroup III. The switch from the variable to the constant part occurs at position 126/127, thus making VH-KOL one of the longest variable parts among the yet known immunoglobulin H-chains. This is due to the hypervariable region Hhv4 which is made up by 17 amino acid residues (4-9 residues more compared with other VH-parts). Within this region a so far not described additional intrapeptidal disulfide bridge could be localized (Cys 105-Cys 110) that creates a short loop with antiparallel running peptide strains in beta-pleated sheet conformation. Its role in the three-dimensional structure of the antigen-binding site of the IgG1 KOL molecule is discussed using the data obtained from X-ray diffraction analysis.
 ...
PMID:[Three-dimensional structure determination of antibodies. Primary structure of crystallized monoclonal immunoglobulin IgG1 KOL, I]. 688 94

Different clones of mouse hybridomas, derived from the fusion of unstimulated mouse peritoneal cells with mouse myeloma cells, producing IgM monoclonal antibodies directed against the membrane of bromelain-treated mouse erythrocytes (MRBC(Br)) have been previously established. We have recently shown that one of these hybridomas produce, in ascites, antibodies cross-reacting with phosphorylcholine derivatives (trimethylammonium (TMA) derivatives). In this work the cross-reactivity for TMA derivatives of the monoclonal antibodies produced by 4 anti-MRBC(Br) hybridomas have been studied at the cell level (plaque-forming cells). Phosphorylcholine, choline bromide and p-aminophenyl-trimethylammonium were found to be potent specific inhibitors of plaque formation (anti MRBC(Br)). The hemolytic activities of ascites and tissue culture supernatants were studied and their inhibition by TMA derivatives was determined. Immunoglobulins from ascites purified on TMA immunoadsorbent column were analyzed by two-dimensional gel electrophoresis, their spectrotype was compared to the spectrotype of immunoglobulins from tissue culture supernatants from the same hybridoma radioactively tagged by internal incorporation of [14C]leucine. It could be shown without ambiguity that the PTMA column retained an IgM with the same characteristics as the IgM secreted in vitro.
 ...
PMID:Relationship between choline derivatives and mouse erythrocyte membrane antigens revealed by mouse monoclonal antibodies. I. Anticholine activity of anti-mouse erythrocyte monoclonal antibodies. 715 55

Rat monoclonal antibody (MoAb) to fragment D (FgD) of human fibrinogen was used to characterize the direct binding of antibody to protein in solution or bound to solid supports. Purified IgG, F(ab')2 and Fab' were prepared from ascites fluid of hybridoma 104-14B which is a fusion product of spleen cells from a rat immunized with FgD and the mouse myeloma cell line, P3-X63-Ag8. Two-dimensional electrophoresis of radioiodinated antibody preparations demonstrated the presence of hybrid immunoglobulin molecules, but only structures having rat heavy and rat light chains had active antibody combining sites. The affinity constant for IgG as well as F(ab')2 and Fab', 6 X 10(9) M-1, was identical when tested using fluid phase antigen (125I-labeled FgD). Affinity constants determined for direct binding of iodinated IgG using FgD immobilized on solid supports showed a slight dependence on the antigen concentration used in the measurement. These values ranged from 0.5 X 10(9) M-1 at high antigen concentrations (1.3 X 10(-7) M) to 9 X 10(9) M-1 at low antigen concentration (1.3 X 10(-10) M). Binding constants for F(ab')2 and Fab' gave similar results indicating that binding was homogeneous and univalent. The capacity of solid state antigen to bind antibody varied with the method used to bind FgD to the solid support. FgD bound directly to polystyrene plates was least efficient at binding labeled antibody; FgD bound to plates through intermediate carriers poly(L-lysine) was only slightly more efficient, while antigen bound to Sepharose beads by cyanogen bromide activation was the most active.
 ...
PMID:Binding of monoclonal antibody to protein antigen in fluid phase or bound to solid supports. 715 17

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.
 ...
PMID:Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy. 752 6

A study was made of the effects of inhibitors of ATP synthesis on the process of rhodamine 123 (R-123) release from sensitive sp2/0-Ag14 cells, multidrug-resistant mouse myeloma spEBR-5 cells and hybridoma IF7, derived from spEBR-5 cells. It has been shown that IF7 cells are cross-resistant to ethidium bromide, colchicine, actinomycin D and adriamycin. However, hybridoma IF7 cells, compared to parental spEBR-5 cells, show a lower resistance index. When studying the dependence of the R-123 efflux rate on glycolysis intensity (effect of 2 mM 2-deoxyglucose) and on the level of oxidative phosphorylation activity (effect of 2 mM KCN and 30 microM dinitrophenol), the following distinctive properties of the R-123 transport system of IF7 cells (compared to spEBR-5 cells) were detected: 1) uptake of R-123 into IF7 cells is similar to that observed for the sensitive sp2/0-Ag14 cells; 2) efflux of R-123 from IF7 cells takes place more intensely; 3) R-123 transport is dependent on the rate of glycolysis and may be inhibited by KCN. It is found that 2,4-dinitrophenol inhibits the R-123 efflux from all the cells. Verapamil reverses the multidrug resistance both in spEBR-5 and IF7 cells. The mechanisms of multidrug resistance of cells are discussed.
 ...
PMID:[The kinetics of rhodamine 123 efflux from cells with multiple drug resistance under the action of energy metabolism inhibitors]. 757 Oct 15

It is now well documented that apoptosis represents the prevalent mode of cell death in hybridoma cultures. Apoptotic or programmed cell death occurs spontaneously in late exponential phase of batch cultures. Until lately, no specific triggering factors had been identified. Recently, we observed that glutamine, cystine or glucose deprivation induced apoptosis in both hybridoma and myeloma cell lines whereas accumulation of toxic metabolites induced necrotic cell death in these cells. Other triggering factors such as oxygen deprivation might also be responsible for induction of apoptosis. In the present study, induction of cell death by exposure to anoxia was examined in batch culture of the SP2/0-derived hybridoma D5 clone. The mode of cell death was studied by morphological examination of acridine orange-ethidium bromide stained cells in a 1.5 L bioreactor culture grown under anoxic conditions for 75 hours. Under such conditions, viable cell density levelled off rapidly and remained constant for 25 hours. After 45 hours of anoxia, cell viability had decreased to 30% and the dead cell population was found to be 90% apoptotic. In terms of cellular metabolism, anoxia resulted in an increase in the utilization rates of glucose and arginine, and in a decrease in the utilization rate of glutamine. The lactate production rate and the yield of lactate on glucose increased significantly while the MAb production rate decreased. These results demonstrate that glycolysis becomes the main source of energy under anoxic conditions. Cells incubated for 10 hours or less under anoxic conditions were able to recuperate almost immediately and displayed normal growth rates when reincubated in oxic conditions whereas cells incubated for 22 hours or more displayed reduced growth rates. Nonetheless, even after 22 h or 29 h of anoxia, cells reincubated in oxic conditions showed no further progression into apoptosis. Therefore, upon removal of the triggering signal, induction of apoptosis ceased.
 ...
PMID:Induction of apoptosis in oxygen-deprived cultures of hybridoma cells. 776 24

Stable mutant cells spEBR-5, resistant to ethidium bromide in concentration of 5 micrograms/ml, have been isolated by multistep selection in mouse myeloma cells sp2/0-Ag14. The spEBR-5 cells, selected with ethidium bromide, appeared to be cross resistant to unrelated drugs in connection with mdr/lb gene amplification and overexpression. Five specific chromosomal markers were detected in the karyotype of spEBR-5 cells as a result of chromosome structural rearrangement. No cytological manifestation of gene amplification such as HCR of chromosomes or DMs was found. A diffuse location of amplified sequences in chromosome(s) is suggested. The new mutant cell lines spEBR-5 can be used as a model for investigation of multidrug resistance mechanisms.
 ...
PMID:[The isolation and genetic characteristics of the new cell line of mouse myeloma spEBR-5 selected for ethidium bromide resistance and characterized by multiple drug resistance]. 790 Feb 9

A toxic phospholipase A2 (PLA2) was isolated from Taiwan-habu-snake (Trimeresurus mucrosquamatus) venom by sequential chromatographies on CM-52, Sephadex G-75 and S-Sepharose columns. This basic PLA2 has a single polypeptide with an estimated M(r) of 15,000. The PLA2 activity was Ca(2+)-dependent and inactivated by p-bromophenacyl bromide and its specific antibody. The toxic PLA2-induced myotoxic and direct haemolytic effects as well as respiratory distress in mice with an intraperitoneal LD50 of 1.17 micrograms/g body weight. The histological examination showed it caused haemorrhage and congestion in the viscera of mice. It was also cytotoxic to myeloma cells (NS-1), baby-hamster-kidney (BHK) cells and human umbilical endothelial cells. By neutralization experiments with a specific antibody against toxic PLA2, it was found that the enzymic activity of toxic PLA2 is essential for its myotoxicity, but it is not the only factor responsible for the lethal toxicity.
 ...
PMID:Isolation and characterization of a toxic phospholipase A2 from the venom of the Taiwan habu (Trimeresurus mucrosquamatus). 813 82

We report here that cultured human lymphoma cells in the absence of sonicated eosinophils are sensitive to killing by glucose oxidase (beta-D-glucose:oxygen-oxido reductase; EC 1.1.3.4) at concentrations as low as 0.025 microgram/ml, a level that can be rapidly attained in s.c. tumor implants in mice that receive a single nonlethal injection of enzyme. Multiple clonogenic assays were used to measure the survival of human lymphoma cell lines (H9 and ARH-77) cultured for 14 days in complete RPMI 1640 supplemented with exogenous glucose oxidase (0.025-2.5 micrograms/ml) or an immunoconjugate containing glucose oxidase (0.25-25 micrograms/ml) in the presence or absence of catalase (10 micrograms/ml) or an equal number of sonicated human eosinophils with or without supplemental 100 microM Br-, I-, or SCN-. In addition, we used an immunoassay to measure the concentration of glucose oxidase in s.c. implants of the Sp 2/0 myeloma tumor at 0-30 min after an i.v. injection of 50 micrograms of enzyme into 21 BALB/c mice. Doses of glucose oxidase as small as 0.025 microgram/ml killed more than 3 logs of tumor cells. Catalase completely inhibited, and sonicated human eosinophils partially inhibited, the killing by glucose oxidase or immunoconjugate, whereas supplemental halides had no effect. Glucose oxidase i.v. produced levels > 0.04 microgram/g of tumor for 30 min after injection with a peak concentration of 0.079 microgram/g of tumor within 5 min of injection. These results are important because certain human lymphomas contain extensive extracellular deposits of eosinophil peroxidase, thereby making these tumors potentially less susceptible to killing by otherwise therapeutic doses of glucose oxidase.
 ...
PMID:Effects of sonicated eosinophils on the in vitro sensitivity of human lymphoma cells to glucose oxidase. 816 93


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