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 cells and mitochondria had the same kinds of cytochrome components in the respiratory chain as the normal ones. Their constitution, however, was abnormally different from that found in normal cells and mitochondria. The cytochrome aa3 concentration was especially low in the myeloma as compared with cytochrome c concentration, and the resulting cytochrome aa3/c ratio was 0.25, which was the lowest ever reported in animal mitochondria. Normal lymph node cells, producing the immunoglobulin similar to the myeloma cells, had a ratio of 1.1. Human myeloma mitochondria had the same characteristics as the mouse myeloma. Ascite form myeloma originated from mouse solid from myeloma grew faster, and yet aa3/c of 0.5 in the ascites myeloma was found to be quite similar to that observed in various ascites tumor cells such as hepatomas, Ehrlich and sarcoma 180. A significant part of the cytochromes in the respiratory chain of the mouse myeloma remained in the oxidized form in the cyanide-inhibited or anaerobic states, and was reduced only by the addition of dithionite. The properties of the b cytochromes in mouse myeloma mitochondria are also described and discussed in the context of multiple forms of the b cytochromes in the respiratory chain.
 ...
PMID:An abnormal ratio of cytochromes in the respiratory chain of mouse and human myelomas. 125 59

The chick kidney mitochondrial cytochrome P-450 1,25-dihydroxyvitamin D3 24-hydroxylase was partially purified by sequential polyethylene glycol precipitation, aminohexyl-Sepharose 4B, and hydroxylapatite chromatography. The specific activity of the final preparation, when reconstituted with NADPH, adrenodoxin, and adrenodoxin reductase, was 245 pmol/min/mg of protein or 0.56 pmol/min/pmol of P-450. The specific cytochrome P-450 content was 0.45-0.73 nmol/mg of protein. BALB/c mice immunized with this preparation developed serum polyclonal antibodies to the 24-hydroxylase, as demonstrated by immunoprecipitation. Splenic lymphocytes from an immunized mouse were fused with myeloma NSI/1-Ag-4-1 cells, and hybridomas secreting monoclonal antibodies to the 24-hydroxylase were detected by immunoprecipitation. The hybridoma lines were cloned by limiting dilution and further characterized as IgG1, IgG3, and IgM subclasses. In one-dimensional immunoblots of soluble 24-hydroxylase preparations, the monoclonal antibodies revealed a single band with an apparent molecular weight of 59,000. The monoclonal antibodies did not cross-react with cytochrome P-450s from other species but immunoprecipitated and immunoblotted a soluble chick renal mitochondrial 25-hydroxyvitamin D3 1 alpha-hydroxylase preparation, demonstrating the close similarity of these two hydroxylases. These antibodies were coupled to Sepharose CL-4B and used to isolate to homogeneity the two enzymes from chick kidney mitochondria. Amino-terminal sequences and amino acid composition data demonstrate that these enzymes are different but homologous.
 ...
PMID:Immunopurified 25-hydroxyvitamin D 1 alpha-hydroxylase and 1,25-dihydroxyvitamin D 24-hydroxylase are closely related but distinct enzymes. 131 Jun 88

Ten monoclonal antibodies reactive with a high spin form of rat cytochrome P-448 (P-448-H) were obtained from hybridoma clones established by a fusion between P3X63Ag8.653 mouse myeloma cells and spleen cells of a BALB/c mouse hyperimmunized with the cytochrome. One monoclonal antibody recognized an epitope characteristic for P-448-H. Five monoclonal antibodies were cross-reactive with a low spin form of rat cytochrome P-448, but not with cytochrome P-450. Reactivity of these monoclonal antibodies with microsomes of rats pretreated with drug metabolizing inducers and Western blots of the microsomal cytochrome P-450 components are also demonstrated.
 ...
PMID:Monoclonal antibodies against a high spin form of rat cytochrome P-448. 241 46

Hybridomas were prepared from myeloma cells and spleen cells of BALB/c female mice immunized with hepatic cytochrome P-450E purified from the marine fish, Stenotomus chrysops (scup). Nine independent hybrid clones produced MAbs, either IgG1, IgG2b, or IgM, that bound to purified cytochrome P-450E in radioimmunoassay. Antibodies from one clone MAb (1-12-3), also strongly recognized rat cytochrome P-450MC-B (P-450BNF-B; P-450c). The nine antibodies inhibited reconstituted aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin O-deethylase of scup cytochrome P-450E to varying degrees, and inhibited AHH activity of beta-naphthoflavone-induced scup liver microsomes in a pattern similar to that in reconstitutions, indicating that cytochrome P-450E is identical to the AHH catalyst induced in this fish by beta-naphthoflavone. MAb 1-12-3 also inhibited the reconstituted AHH activity of the major BNF-induced rat isozyme. Conversely, MAb 1-7-1 to rat cytochrome P-450MC-B had little effect on AHH activity of scup cytochrome P-450E, and did not recognize cytochrome P-450E in radioimmunoassay nor in an immunoblot. Scup cytochrome P-450E and rat cytochrome P-450MC-B thus have at least one common epitope recognized by MAb 1-12-3, but the epitope recognized by Mab 1-7-1 is absent or recognized with low affinity in cytochrome P-450E. The various assays indicate that the nine MAbs against cytochrome P-450E are directed to different epitopes of the molecule. These MAbs should be useful in determining phylogenetic relationships of the BNF- or MC-inducible isozymes and their regulation by other environmental factors.
 ...
PMID:Monoclonal antibodies to liver microsomal cytochrome P-450E of the marine fish Stenotomus chrysops (scup): cross reactivity with 3-methylcholanthrene induced rat cytochrome P-450. 242 9

Polyclonal antibody elicited in a rabbit against purified cytochrome P-450cc25, which catalyzes 25-hydroxylation of vitamin D3, inhibited not only 25-hydroxylation of cholecalciferol and 1 alpha-hydroxycholecalciferol, but also 16 alpha- and 2 alpha-hydroxylation of testosterone catalyzed by the purified P-450cc25 preparation. Antibody inhibition experiments with microsomes revealed that most 16 alpha- and 2 alpha-hydroxylation of testosterone and most 25-hydroxylation of cholecalciferol by male rat liver microsomes were catalyzed by P-450cc25. In order to examine the identity of cholecalciferol 25-hydroxylase and testosterone 16 alpha-hydroxylase, monoclonal antibodies recognizing three different epitopes of P-450cc25 were prepared from hybridoma clones produced by fusion of mouse myeloma cells (P3X63Ag8U1) with the spleen cells of immunized BALB/c mouse. All of these monoclonal antibodies inhibited both 25-hydroxylation of 1 alpha-hydroxycholecalciferol and 16 alpha-hydroxylation of testosterone by purified P-450cc25. These observations suggested that immunochemically indistinguishable form(s) of cytochrome P-450 catalyzed both reactions.
 ...
PMID:Immunochemical evidence for the catalysis of vitamin D3 25-hydroxylation and testosterone 16 alpha-hydroxylation by homologous forms of cytochrome P-450 in rat liver microsomes. 246 Apr 37

Anionic amphiphiles such as long chain unsaturated fatty acids and SDS were shown to activate the superoxide (O2-) producing NADPH oxidase in a cell-free system derived from sonically disrupted phagocytes (macrophages and granulocytes). O2- production required the cooperation of a membrane associated component sedimenting at 48,000 X g (pi) and a cytosolic factor (sigma). The purpose of the present investigation was to find out whether components pi and sigma were also present in non-phagocytic cells that do not produce O2- when stimulated. It was found that the 48,000 X g pellets of guinea pig lymph node and thymus cell sonicates contained significant amounts of component pi, as shown by their ability to support SDS-elicited NADPH-dependent O2- production when supplemented with macrophage cytosol. Lymph node and thymus pi could be extracted from the membrane by 30 mM octyl glucoside, just as its macrophage-derived equivalent. Combining lymph node and thymus 48,000 X g pellet with autologous cytosol did not yield an active enzyme preparation. Also, cytosol from lymph node and thymus cells could not cooperate with macrophage 48,000 X g pellet, indicating that component sigma was lacking in lymphoid cells. Neither pi nor sigma could be detected in guinea pig kidney, the mouse myeloma cell line MOPC 315 and the canine cell line Cf2Th. The 48,000 X g pellet of all nonphagocytic cells examined contained a b-cytochrome that resembled, by its spectral characteristics, the cytochrome b559 thought to be characteristic of phagocytes. In macrophages, cytochrome b559 represented 80% of b-cytochrome content of the 48,000 X g pellet, whereas in non-phagocytic cells, the equivalent material represented only 50 to 60%. There was no correlation between the presence and quantity of the cytochrome b559-like chromophore in the 48,000 X g pellet of a particular cell type and its ability to cooperate with macrophage cytosol in SDS-elicited O2- production.
 ...
PMID:Certain lymphoid cells contain the membrane-associated component of the phagocyte-specific NADPH oxidase. 283 Dec 70

Spleen cells from a BALB/cByJ mouse previously immunized with purified rat liver microsomal cytochrome P-450c were fused with myeloma cells (P3X63Ag8.653) and 10 hybridoma clones secreting antibody against cytochrome P-450c were selected for characterization. The monoclonal antibodies (C1-C10) were purified from mouse ascites fluid and nine were determined to be distinct immunoglobulins. C6 was an IgG2b, whereas the rest were of the IgG1 subclass. A competitive enzyme-linked immunoassay was used to show that the antibodies were directed against at least five spatially distinct epitopes on cytochrome P-450c. Additional evidence for the recognition of distinct epitopes was provided by Ouchterlony immunoprecipitation of cytochrome P-450c with mixtures of appropriate monoclonal antibodies. Differences in antibody reactivity provided evidence for a sixth overlapping epitope that was recognized by two antibodies (C4 and C6). Three monoclonal antibodies to the same epitope on cytochrome P-450c, (CD2, CD3, and CD5) cross-reacted strongly with cytochrome P-450d, another isozyme induced by 3-methylcholanthrene treatment of rats. The antibodies that did not cross-react with cytochrome P-450d contained kappa light chains, whereas the three cross-reacting antibodies contained lambda light chains. None of the monoclonal antibodies cross-reacted with purified cytochromes P-450a, P-450b, P-450e, P-450f, P-450g, or P-450h or any other cytochrome P-450 in "Western blots" of liver microsomes from untreated or 3-methylcholanthrene-treated rats. C8 was a potent inhibitor of metabolism catalyzed by cytochrome P-450c in a reconstituted system as well as microsomes from 3-methylcholanthrene-treated rats. This antibody effected maximal inhibition of catalytic activity at an approximately 0.5:1 molar ratio of IgG to cytochrome P-450c, i.e. one antibody-binding site per epitope on cytochrome P-450c.
 ...
PMID:Characterization of nine monoclonal antibodies against rat hepatic cytochrome P-450c. Delineation of at least five spatially distinct epitopes. 670 86

Monoclonal antibodies were prepared from hybridoma clones isolated by the fusion of myeloma cells and spleen cells derived from mice immunized with either purified rabbit liver microsomal cytochrome P-450LM2 or cytochrome P-450LM4. Seven hybridoma clones produced three kinds of monoclonal antibodies to P-450LM2. The first class bound, precipitated, and inhibited the enzyme activity of P-450LM2 for both benzo[a]pyrene hydroxylation and 7-ethoxycoumarin deethylation. The other two classes either bound and precipitated or only bound the enzyme. These monoclonal antibodies to P-450LM2 showed a precipitin reaction and inhibition of enzyme activity that was specific for cytochrome P-450LM2. Thus, they did not react with or inhibit the enzyme activity of the other isozyme cytochrome P-450LM4, Fraction 1 or Fraction 7. All of the monoclonal antibodies formed against P-450LM2 were mouse immunoglobulin (Ig) subclass IgG1. The most effective monoclonal antibody strongly inhibited the formation of oxygenated metabolites of benzo[a]pyrene at various positions as well as the deethylation of 7-ethoxycoumarin. Four hybridomas were isolated which produced monoclonal antibodies to P-450LM4. One of the four was of the IgM class and three were of the IgG1 type. The four monoclonal antibodies bound to P-450LM4 but did not precipitate the enzyme, and did not bind to P-450LM2. The monoclonal antibody P-450LM4 complexes interacted with protein A, and the enzyme activity for benzo[a]pyrene hydroxylation could be removed by centrifugation. The high specificity and monoclonality of these antibodies suggest their potential usefulness for studying the genetics, regulation, and roles of the different isozymes of P-450LM in drug and carcinogen metabolism.
 ...
PMID:Monoclonal antibodies to rabbit liver cytochrome P-450LM2 and cytochrome P-450LM4. 681 77

The viability of neutrophils in the condition under which they kill neoplastic cells was studied. In the presence of phorbol myristate acetate (PMA) the 51Cr-release by human neutrophils was markedly stimulated. The PMA-induced 51Cr-release by neutrophils correlated well with the number of nonviable neutrophils as determined by the uptake of trypan blue. Phorbol myristate acetate had no effect on the 51Cr-release by lymphocytes, LPC-1 myeloma cells, ovarian ascites tumor cells, or neutrophils from a patient with chronic granulomatous disease. This suggests that the effect of PMA is not due to its nonspecific toxic effect; instead, it is dependent on the reactive oxygen species produced by the normal neutrophils. Catalase, cytochrome C, histidine, and methionine inhibited the PMA-induced 51Cr-release by human neutrophils, whereas superoxide dismutase, myeloperoxidase inhibitors, and some hydroxyl radical scavengers or singlet oxygen quenchers had no effect. The clumping of neutrophils induced by PMA was also important in the PMA-induced 51Cr-release by human neutrophils.
 ...
PMID:Phorbol myristate acetate induced neutrophil autotoxicity. 719 15

2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and apoptosis in leukemic cells and is also antiangiogenic. In this study, we demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and induces apoptosis in MM cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of 2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome-c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3. Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2 mediates anti-MM activity directly on MM cells and in the BM microenvironment. They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM.
 ...
PMID:2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells. 1220 Mar 84


1 2 3 4 Next >>