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)

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.
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PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95

Monoclonal antibodies (MAbs) directed against phase I and II variants of Coxiella burnetii were produced by fusing myeloma SP2/O-AG 14 cells with spleen cells from mice immunized with the chloroform-methanol extraction residue of phase I whole cells. Two hybridoma clones which distinguished the phase variants by microimmunofluorescence assay were isolated and characterized. The MAbs showing specificity for phase I cells (MAbI-1, immunoglobulin G, subclass 3 kappa) reacted with the hot phenol-water extract of phase I C. burnetii in immunodiffusion and enzyme-linked immunosorbent assays. MAbI-1 reacted with high-molecular-weight components from phase I phenol-water extract and whole cell in an immunoblot assay. Specificity of MAbI-1 for a carbohydrate epitope in the phenol-water extract was demonstrated by periodic acid inactivation of binding by a competitive enzyme-linked immunosorbent assay. Phase I antigenic sites were apparently well represented on the surface of cells as demonstrated by complete fluorescence and microagglutination. The MAb showing specificity for phase II cells (MAbII-1, immunoglobulin G, subclass 2b kappa) reacted with whole cells in the microimmunofluorescence assay, microagglutination test, complement fixation test, and the enzyme-linked immunosorbent assay. MAbII-1 reacted specifically with a 29,500-dalton surface protein as demonstrated by immunoprecipitation of 125I-surface-labeled cells. Although MAbII-1 reacted with detergent-solubilized protein, it did not react with sodium-dodecyl sulfate-denatured protein by immunoblot assay. This protein was not exposed on the surface of phase I cells, but chloroform-methanol extraction of phase I cells exposed the phase II epitope.
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PMID:Monoclonal antibodies distinguish phase variants of Coxiella burnetii. 641 62

Monoclonal antibodies were prepared by the fusion of murine myeloma NS1 cells with spleen cells of BALB/c mice immunized with Formalin-killed elementary bodies of the Chlamydia trachomatis L2 serovar. The specificity of these monoclonal antibodies was determined with a solid-phase immunoassay in which HeLa 229 cells infected with C. trachomatis serovars D, G, H, I, L2 and the Chlamydia psittaci meningopneumonitis strain Cal-10 were used. An immunoglobulin G3 monoclonal antibody (L2I-6) was identified that reacted with both C. trachomatis- and C. psittaci-infected HeLa cells. The immunoreactivity of the genus-specific epitope was heat resistant (100 degrees C, 10 min) but was destroyed by sodium metaperiodate treatment. Further characterization of the chlamydial specificity of monoclonal antibody L2I-6 by microimmunofluorescence showed that it was reactive with all 15 C. trachomatis serovars and seven C. psittaci strains isolated from five different animal species. We undertook studies to identify the biochemical nature of the chlamydial component on which the genus-specific epitope was located. The immunoreactive component was isolated by hot phenol-water extraction of dithiothreitol-reduced chlamydial elementary bodies. The component was positive in the Limulus amoebocyte lysate test (results of Limulus amoebocyte lysate assay were identical with those of Salmonella typhimurium LT2 SAI 377 Re lipopolysaccharide [LPS]), contained 8.8% 2-keto-3-deoxyoctulosonic acid, was resistant to proteinase K, and possessed electrophoretic mobility and silver-staining characteristics in sodium dodecyl sulfate-polyacrylamide gel electrophoresis consistent with a rough LPS or glycolipid. On the basis of these findings, we conclude that the genus-specific epitope recognized by monoclonal L2I-6 is located on chlamydial LPS. We further characterized the antigenic properties of the chlamydial LPS epitope by examining the immunoreactivity of monoclonal antibody L2I-6 by immunoblotting analyses against isolated LPSs extracted from Neisseria gonorrhoeae, S. typhimurium, and Escherichia coli. Monoclonal antibody L2I-6 did not bind LPS of these organisms, demonstrating that the chlamydial genus-specific LPS epitope is apparently not shared by these gram-negative bacteria. We were able, however, to show that the chlamydial LPS does share antigenic determinants with LPS of gram-negative organisms. Polyclonal rabbit antisera raised against S. typhimurium Re LPS or lipid A showed intense immunological cross-reactivity with chlamydial LPS by immunoblotting.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal antibody against a genus-specific antigen of Chlamydia species: location of the epitope on chlamydial lipopolysaccharide. 642 19

The surface denaturation kinetics of mouse normal IgG and IgGl kappa secreted by myeloma MOPC-21 was studied in monomolecular layers at the air-water interface. Based on the denaturation kinetics data the orientation of the native IgG molecules was determined relative to the interface surface, which turned out to be horizontal for normal IgG and vertical for myelomic ones. As regards the orientation in the monolayers and the rate of surface denaturation, the mouse normal IgG were found to be similar to normal IgG from other species. Like human myelomic IgG, MOPC-21 IgGl kappa differed from normal IgG in both the orientation and lesser native structure stability.
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PMID:[Identical nature of the differences between normal and myeloma IgG in the mouse and man determined by the monolayer method]. 646 35

A monoclonal antibody (MAb) HL-C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/1-AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL-60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL-C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL-60, ML1, ML2, ML3, KG-1B and not with the less differentiated myeloid lines. Fluorescence-activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL-C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL-C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL-C5 was recovered in the upper phase of chloroform-methanol-water lipid extracts prepared from HL-60 cells. By competitive binding experiments, it was found that MAb HL-C5 recognizes the same antigenic determinant as MAb WGHS 29-1, which has been reported to react with glycolipids containing the sugar sequence lacto-N-fucopentaose 111. Autoradiographs of thin layer chromatograms of HL-60 glycolipid extracts which were revealed by incubation with MAb HL-C5 or WGHS 29-1 followed by the addition of 125I-labelled rabbit anti-mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.
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PMID:Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage. 657 67

A protected tridecapeptide, representing a new peptide corresponding to residues 56-68 of the VH domain in the mouse M603 myeloma protein, has been prepared by solid phase peptide synthesis. The protected tridecapeptide was prepared using the photolabile 4-bromomethyl-(3-nitro)-benzamidomethyl-resin and the multidetachable 2-[4-bromomethyl)phenylacetoxy]propionyl-resin as solid supports. The synthetic protocol and protecting groups were the same for both syntheses. The protected tridecapeptide was removed photolytically from both supports and the sequence integrity was determined by preview analysis using the solid phase Edman degradation procedure. The protected tridecapeptide-OMPA was purified to homogeneity by DMF/H2O precipitation and LH-60 chromatography. The purity of the protected peptide was further demonstrated by high pressure liquid chromatography on the free peptide after HF deprotection. The protected tridecapeptide was reattached to 4-bromomethyl-(3-nitro)-benzamidomethyl-resin to give the photolabile Boc-(protected)peptidyl-4-oxymethyl-(3-nitro)benzamidomethyl-resin in 25% yield. The protected tridecapeptide-oxymethylphenylacetic acid derivative was reattached to aminomethyl-resin to give Boc-(protected)peptidyl-2-[4-oxymethyl)phenyl]acetamidomethyl-resin in 45% yield and to 2-bromopropionyl-resin generating the multidetachable Boc-(protected)peptidyl-2-[(4-oxymethyl)phenylacetoxy] propionyl-resin in 80% yield. The reactivity of these reattached peptides was demonstrated by the quantitative coupling of Boc-leucine to the protected peptide-resin. The advantages and disadvantages of the different resins with respect to solid phase fragment synthesis are discussed.
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PMID:Synthesis of the protected tridecapeptide (56-68) of the VH domain of mouse myeloma immunoglobulin M603 and its reattachment to resin supports. 661 64

Monoclonal antibodies (MA) were prepared by the fusion of spleen cells from C57BL/6J mice infected with Schistosoma mansoni with non-secreting SP2 myeloma cells. Clones of fused cells secreting MA reactive with the egg and cercarial antigens (as determined by the enzyme-linked immunosorbent assay), as well as with schistosomules (as determined by immunofluorescence), were injected into pristane "primed" mice to produce ascitic fluid. Cercariae were treated with MA by incubating them in individual MA or a pool of 3 or 4 MA (0.25 ml each) in form of ascitic fluid diluted in 10 ml of snail water for 60-90 minutes prior to snail exposure. Groups of 7-9 mice were exposed to MA-treated cercariae either via the tail or intraperitoneally (i.p.). Control mice were exposed to non-treated cercariae or those which were treated with nonsense ascitic fluid. Maturing adult worms were recovered by the perfusion technique and counted. The results of two experiments indicate that cercariae treated with a pool of 3 or 4 MA fail to penetrate the skin of mice and thus were not able to develop into adult worms. Treatment of cercariae with 1 MA resulted in a very low worm recovery (4.3% of the exposure dose). The rate of worm recovery from mice injected i.p. with pool-treated cercariae was similar to that recovered from control mice. In contrast to control groups, mice injected with MA-treated cercariae had a higher percentage of immature worms which may indicate a possible form of stunting phenomenon associated with MA-treatment.
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PMID:The effect of monoclonal antibodies on Schistosoma mansoni cercarial penetration of mouse skin. 666 11

Human corneal epithelial water insoluble proteins were used to immunize mice. Immune splenocytes were fused with Sp 2/0-Ag14 mouse myeloma cells by 40% PEG. Hybridoma antibodies obtained by somatic cell fusion were tested by radioimmunoassay. Supernatants from antibody positive hybrid colonies were used in immunofluorescence and crossreaction assays to locate and characterize corneal epithelial antigens. At least three distinct epithelial cell antigens were detected, one of which cross-reacts with rabbit corneal epithelial cells.
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PMID:Hybridoma antibodies to insoluble antigens of the corneal epithelium. 675 52

Sodium was determined by flame photometry and by direct potentiometry in 56 serum or plasma samples from 24 patients with multiple myeloma or macroglobulinemia. We observed differences between the two techniques as large as 17 mmol/L (12%). The flame-photometric values decreased relative to the direct-potentiometric values as protein increased or water content decreased. Moreover, the two sodium measurements could not be interconverted simply on the basis of correcting for protein or water content. There was significantly lower residual variance (p less than 0.005) when the direct-potentiometric sodium values were compared with the osmolality (corrected for the influence of glucose and urea nitrogen) than when the flame-photometric values for sodium were so compared. We conclude that direct potentiometric measurements of sodium in patients with multiple myeloma gives clinically relevant results but flame photometry does not. Clearly, the method by which sodium is measured in patients with multiple myeloma must be considered if results are to be interpreted correctly.
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PMID:Sodium measurements in multiple myeloma: two techniques compared. 681 89

Orientation of normal and 12 abnormal immunoglobulins G (IgG) isolated from serum of patients with multiple myeloma in monomolecular layers at 0.15 M NaCl--air and 0.15 M NaCl--octane interfaces has been studied. Majority of abnormal proteins was found to be oriented vertically at phase border of both types unlike normal human IgG which had horizontal orientation. Abnormal IgG differed from the normal one also by lower resistance to surface denaturation at air--water interface. Thus the monomolecular layer method was demonstrated to be capable of distinguishing normal and abnormal IgG.
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PMID:[Comparative study of normal and myelogenic immunoglobulin G in monomolecular layers at air-water and oil-water interface]. 687 Dec 63


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