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)

An ATPase was purified from mouse myeloma MOPC 70E the activity of which depends on the presence of single-stranded DNA and divalent cations such as Mg2+, Mn2+, Ca2+, Ni2+ or Fe2+. The enzyme splits both ribonucleoside and deoxyribonucleoside triphosphates but preferentially ATP and dATP yielding nucleoside diphosphates and inorganic phosphate. The enzyme has an absolute requirement for single-stranded DNA. Alternating double-stranded polydeoxynucleotides are only slight effective, and native double-stranded DNA, single-stranded and double-stranded RNAs as well as DNA - RNA hybrids are ineffective in stimulating the ATPase. The enzyme has further characterized by sedimentation in a sucrose density gradient (s20, w = 5.5 S) and by isoelectric focussing in an ampholine pH gradient (pI = 6.5).
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PMID:An ATPase depending on the presence of single-stranded DNA from mouse myeloma. 12 26

The mortality experience of 716 male hydrometallurgical nickel refinery employees who worked at Sherritt Gordon Limited in Fort Saskatchewan, Alberta for at least 12 continuous months during the years 1954 to 1978 was examined. Mortality ascertainment was obtained utilizing the Canadian Mortality Data Base maintained by Statistics Canada and covered the years 1954 through 1984. Cause-specific mortality analyses were accomplished using male, age and calendar-year adjusted death rates for Canada and the province of Alberta. Total mortality was significantly below expectation (27 observed vs. 47 expected). Statistically significant fewer observed deaths were found for circulatory disease while multiple myeloma demonstrated a statistically significant increase of observed deaths. No deaths due to nasal cavity or paranasal sinus cancer were detected. Only one lung cancer death was found with three deaths expected (SMR 33). No association was found in this study between exposure to nickel concentrate or metallic nickel and the subsequent development of respiratory cancer.
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PMID:Mortality experience at a hydrometallurgical nickel refinery in Fort Saskatchewan, Alberta between 1954 and 1984. 201 Oct 3

A five-year extension to an ongoing epidemiology study has been undertaken. Mortality information was updated for an additional five years through 1985-1989 for 715 male hydrometallurgical nickel refinery employees who worked at Sherritt Gordon Limited in Fort Saskatchewan, Alberta, during the years 1954 to 1978. Mortality ascertainment was obtained using the Canadian Mortality Data Base, maintained by Statistics Canada, and covered the years 1954 through 1989. Cause-specific mortality analyses were accomplished for males, by age group and calendar year of death, for Canada and the province of Alberta. Total mortality was significantly below expectation (42 observed vs. 70 expected deaths for Canada, and 66 expected for Alberta). Statistically fewer observed deaths were found for circulatory disease while multiple myeloma and lymphoid malignancies demonstrated a statistically significant increase of observed deaths. Specific focus was directed at cancers of the respiratory system because of previous reports linking these conditions with exposure to nickel compounds in some workforces. No deaths due to nasal cavity or paranasal sinus cancer were detected among cohort or study group members. Four lung cancer deaths were found with five deaths expected for Canada and four expected for Alberta. To date, no association between exposure to nickel concentrate or metallic nickel and the subsequent development of respiratory cancer has been found in this study. The hydrometallurgical refinery operation is an enclosed process in contrast to other refinery processes such as pyrometallurgical and electrolytic.
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PMID:An update of an epidemiology study at a hydrometallurgical nickel refinery in Fort Saskatchewan, Alberta. 819 31

Sensitivity to nickel, cobalt, and chromium is common among the general population. The identification of these sensitivities is generally by the detection of cell-mediated immunity. We have reported previously the use of an indirect enzyme-linked immunosorbent assay method to quantitate metal-specific antibodies in patients with total joint replacements. To study the haptenic potential of these metal ions, rabbit albumin-glutathione-metal complexes with chromium, cobalt, or nickel were injected into mice. The splenocytes from one mouse in each group which developed a strong antibody against GSH-metal complexes were isolated and fused with myeloma cells to produce monoclonal antibodies. Chromium, cobalt, and nickel antibodies had similar affinity and bound with the specific GSH-metal complex. There was very little cross-reactivity between these antibodies. An inhibition assay using these monoclonal antibodies was demonstrated to be a simple technique, suitable for quantitation of free metal in solution.
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PMID:Production of monoclonal antibodies to study corrosion products of CO-CR biomaterials. 873 Nov 51

Oral administration of rabbit secretory IgA (sIgA) to adult BALB/c mice induced IgA+, IgM+, and IgG+ lymphoblasts in the Peyer's patches, whose fusion with myeloma cells resulted in hybridomas producing IgA, IgM, and IgG1 antibodies to the secretory component (SC). This suggests that SC could serve as a vector to target protective epitopes into mucosal lymphoid tissue and elicit an immune response. We tested this concept by inserting a Shigella flexneri invasin B epitope into SC, which, following reassociation with IgA, was delivered orally to mice. To identify potential insertion sites at the surface of SC, we constructed a molecular model of the first and second Ig-like domains of rabbit SC. A surface epitope recognized by an SC-specific antibody was mapped to the loop connecting the E and F beta strands of domain I. This 8-amino acid sequence was replaced by a 9-amino acid linear epitope from S. flexneri invasin B. We found that cellular trafficking of recombinant SC produced in mammalian CV-1 cells was drastically altered and resulted in a 50-fold lower rate of secretion. However, purification of chimeric SC could be achieved by Ni2+-chelate affinity chromatoraphy. Both wild-type and chimeric SC bound to dimeric IgA, but not to monomeric IgA. Reconstituted sIgA carrying the invasin B epitope within the SC moiety triggers the appearance of seric and salivary invasin B-specific antibodies. Thus, neo-antigenized sIgA can serve as a mucosal vaccine delivery system inducing systemic and mucosal immune responses.
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PMID:A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route. 896 37

In order to detect the protein delivery mediated by the PTD (protein transduction domain) of TAT Protein, a expression vector, named pT7460-GFP, was constructed by insert the PTD DNA Sequence, followed by a GFP (green fluorescent protein) gene fused in-frame, into the pT7450 vector. The TAT-GFP fusion protein was expressed in the E. coli ER2566. Most of the fusion protein was presented in the inclusion body. The protein was purified by Ni2+ affinity chromatography under denature conditions, then by a Sepharose Q column to remove urea. The soluble denatured protein was added directly to medium containing the Myeloma Cell SP2/0. It came out that the fusion protein could be detected delivered into the cells under fluorescent microscope in a short time.
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PMID:[The PTD domain of Tat protein enhance GFP protein delivering into myeloma cell SP2/0]. 1256 Dec 18

IL-15 and IL-15 receptors (IL-15R) play a crucial role in the pathogenesis of adult T-cell leukemia (ATL), multiple myeloma and inflammatory autoimmune diseases. To develop a novel therapeutic agent capable of eliminating IL-15R-over-expressing abnormal cells, the gene coding for human IL-15 antagonist (IL-15M) was fused with a DNA fragment coding for the mutated form of Pseudomonas exotoxin, PEdelta293. The resulting gene fusion was cloned into pET16b under the control of T7 promoter, giving rise to the expression plasmid pET-IL15M-PEdelta293. Using Ni2+ -NTA affinity chromatography, IL15M-PEdelta293 was purified from E. coli BL21 (DE3) pLysS transformed with pET-IL15M-PEdelta293. The fusion toxin showed cytotoxicity to IL-15R-bearing myelogenous leukemia cell line K562 and K562-derived multidrug resistant cell line K562/AO2. However, IL-15R negative cell line Jurkat was insensitive to IL15M-PEdelta293. In addition, the toxic effect of IL15M-PEdelta293 on K562 was completely blocked by excessive amount of recombinant human IL-15. These results demonstrated that the selective cytotoxicity of IL15M-PEdelta293 correlated with the appropriate IL-15R expression on target cells. The present data suggest that the chimeric toxin constructed in this report may have therapeutic potential in the treatment of diseases associated with abnormal expression of IL-15/IL-15R, even in the treatment of chemotherapy refractory tumors.
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PMID:[Development of a fusion toxin IL15M-PEdelta293 based on a receptor-specific IL-15 antagonist]. 1585 27

B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) family. It is required for B cell development. Deregulation of BLyS was involved in the pathogenesis of B cell-related autoimmune diseases and multiple myeloma. To prepare monoclonal antibodies (MAbs) against BLyS, cDNA encoding soluble BLyS (sBLyS) was first amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers, and then inserted into a prokaryotic expression vector pET-30a. Right recombinant plasmid was expressed in Escherichia coli strain BL21(DE3), purified by nickel affinity chromatography. Isolated sBLys was used as an antigen to immunize mice. Splenocytes of one immunized mouse were fused with NS- 1. Hybridomas secreting antibodies against sBLyS were identified by ELISA. One positive clone was selected to produce antibody by injecting the hybridoma into the peritoneal cavity of mice. After collecting ascites, the antibody was purified by protein A affinity chromatography. Western blot and immunoflourescence demonstrated that the antibody could bind recombinant sBLyS and genuine membrane-bound BLyS (mBLyS) on U937. This MAb can be used as a detecting reagent to analyze the serum level of BLyS in patients with autoimmune diseases and the expression profile of mBLyS on multiple myeloma cells.
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PMID:Preparation and characterization of a monoclonal antibody against human B lymphocyte stimulator. 1670 8

Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of acute promyelocytic leukemia with giving a complete remission rate of 83-95%. ATO also shows significant activity in relapsed/refactory multiple myeloma; however, efforts to expand clinical utility to other cancers have been limited by its toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III) materials exhibit a significantly attenuated cytotoxicity that undergoes pH-triggered release of an active drug. The arsenic drugs are loaded into 100-nm-scale liposomes at high concentration (>270 mM) and excellent retention (shelf life > 6 months at 4 degrees C), as determined by inductively coupled plasma optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous acid crosses the bilayer membrane in exchange for acetic acid and an insoluble transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resultant liposomal arsenic nanoparticles appear to be stable in physiological situations but release the drug cargo in a lower pH environment, as encountered in intracellular endosomes. These drugs exhibit attenuated cytotoxicities against human lymphoma tumor cells compared with that of free As2O3. Controlled release of arsenic drugs, and hence control of toxicity, is feasible with this system. The results demonstrate that cytotoxicity can be controlled via transitions of the inorganic drug between solid and solution phases and suggest a mechanism for further improvement of the risk/benefit ratio of As2O3 in treatment of a variety of cancers.
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PMID:Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release. 1703 34

Monoclonal antibodies against lead were generated by immunizing BALB/c mice with lead conjugated to keyhole limpet hemocyanin (KLH) via a bifunctional chelator, S-2-(4-aminobenzyl)diethylenetriamine pentaacetic acid (DTPA). Stable hybridoma cell lines were produced by fusion of murine splenocytes and SP2/0 myeloma cells. One of the hybridomas generated from this fusion (4/7) synthesized and secreted an antibody that bound tightly to Pb2+-DTPA complexes but not to metal-free DTPA. The performance for a competitive inhibition enzyme-linked immunosorbent assay (ELISA) incorporating this antibody was assessed for its sensitivity to changes in pH, ionic strength, and blocking reagents. The cross-reactivities in this ELISA were less than 3% for Fe3+, Cd2+, Hg2+, and Cu2+ and less than 0.3% for Cr3+, Mn2+, Mg2+, In3+, Ag1+, Ni2+, Co2+, Zn2+, Ca2+, Cu1+, and Hg1+. The IC50 value achieved for lead was 2.72 +/- 0.034 microM, showing the detection range of 0.092-87.2 microM and the lowest detection limit of 0.056 +/- 0.005 microM. Recoveries from the analyte-fortified tap water and ultrapure water were in the range of 80-114% . These results indicate that the ELISA could be a convenient analytical tool for monitoring lead residues in drinking water.
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PMID:Characterization of monoclonal antibodies for lead-chelate complexes: applications in antibody-based assays. 1754 20


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