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)

Urokinase-related proteins in human urine occur mainly as a 1:1 complex of urokinase with an inhibitor (Stump, D. C., Thienpont, M., and Collen, D. (1986) J. Biol. Chem. 261, 1267-1273). BALB/c mice were immunized with this urokinase-urokinase inhibitor complex and spleen cells fused with mouse myeloma cells, resulting in hybridomas producing monoclonal antibodies. Three antibodies reacting with the complex but not with urokinase were utilized to develop a sensitive (0.5 ng/ml) enzyme-linked immunosorbent assay for the urokinase inhibitor, which was used for monitoring its purification by chromatography on zinc chelate-Sepharose, concanavalin A-Sepharose, SP-Sephadex C-50, and Sephadex G-100. A homogenous glycoprotein of apparent Mr 50,000 was obtained with a yield of 40 micrograms/liter urine and a purification factor of 320. One mg of the purified protein inhibited 35,000 IU of urokinase within 30 min at 37 degrees C. This protein was immunologically related to both the purified urokinase-urokinase inhibitor complex and to the inhibitor portion dissociated from it by nucleophilic dissociation. It was immunologically distinct from all known protease inhibitors, including the endothelial cell-derived fast-acting inhibitor of tissue-type plasminogen activator, the placental inhibitor of urokinase and protease nexin. In electrophoresis the protein migrated with beta-mobility. Inhibition of urokinase occurred with a second order rate constant (k) of 8 X 10(3) M-1 s-1 in the absence and of 9 X 10(4) M-1 s-1 in the presence of 50 IU of heparin/ml. The urokinase inhibitor was inactive towards single-chain urokinase-type plasminogen activator and plasmin, but it inhibited two-chain tissue-type plasminogen activator with a k below 10(3) M-1 s-1 and thrombin with a k of 4 X 10(4) M-1 s-1 in the absence and 2 X 10(5) M-1 s-1 in the presence of heparin. The concentration of this urokinase inhibitor in plasma from normal subjects determined by immunoassay was 2 +/- 0.7 micrograms/ml (mean +/- S.D., n = 25). The protein purified from plasma by immunoabsorption had the same Mr, amino acid composition, and immunoreactivity as the urinary protein. Furthermore, when urokinase was added to plasma, time-dependent urokinase-urokinase inhibitor complex formation was observed at a rate similar to that observed for the inhibition of urokinase by the purified inhibitor from urine. This urokinase inhibitor, purified from human urine, most probably represents a new plasma protease inhibitor.
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PMID:Purification and characterization of a novel inhibitor of urokinase from human urine. Quantitation and preliminary characterization in plasma. 309 4

A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B-cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B-cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny.
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PMID:Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4). 309 65

Amyloidosis (AL) is a disease characterized by the extracellular deposition of a complex glycoprotein, part of which is derived from light chains of immunoglobulins. The ocular adnexa can be involved in both systemic primary amyloidosis (AL), usually associated with multiple myeloma or other immunologic disorders, or in a localized form without such systemic implications. We present the case report of a 65-year-old man in whom occult primary systemic amyloidosis (AL), associated with a monoclonal IgG-kappa gammopathy, occurred with presenting signs of ptosis and dermatochalasis secondary to infiltration of the extraocular and orbicularis oculi muscles with amyloid.
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PMID:Ptosis and dermatochalasis as presenting signs in a case of occult primary systemic amyloidosis (AL). 311 94

Concanavalin A binding to glycoprotein bands on nitrocellulose blots was used to detect mannose, sorbose, N-acetylgalactosamine and/or glucose residues on 100% (31/31) of human Bence Jones protein light chains, following sodium dodecyl sulphate-polyacrylamide gel electrophoresis. All (20/20) light chains form IgG myeloma proteins and light chains from a preparation of normal polyclonal human IgG were also bound by concanavalin A. The specificity of concanavalin A for glycoproteins was demonstrated by its binding to human Fc fragments and a human monoclonal anti-Rhesus D antibody (REG-A), but not to human albumin pFc' fragments and aglycosylated REG-A derived from cells grown in the presence of the glycosylation inhibitor tunicamycin. These results suggest that all Bence Jones proteins and light chains from myeloma IgG proteins contain mono- or oligosaccharides linked O-glycosidically to serine or threonine residues.
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PMID:Immunogenicity and antigenicity of immunoglobulins: detection of human immunoglobulin light-chain carbohydrate, using concanavalin A. 311 95

The importance of carbohydrate in the secretion of immunoglobulin A (IgA) has previously been suggested by results of studies with tunicamycin, which prevents N-linked glycosylation of all cell glycoproteins. To directly evaluate the role of individual oligosaccharides in the secretion of IgA, we have used site-directed mutagenesis to selectively eliminate the two N-linked attachment sites reported to be glycosylated in alpha heavy chains. Transfected wild-type and mutant alpha genes were expressed in kappa light-chain-producing MPC-11 variant myeloma cells, and secretion kinetics of the IgAs were compared. Removal of either or both glycosylation sites led to intracellular alpha heavy-chain degradation and a 90 to 95% inhibition of IgA secretion. These results reveal that both N-linked oligosaccharides of the alpha heavy chain are essential for intracellular stability and normal secretion of IgA. This suggests that the key function of carbohydrate here is to maintain proper conformation of the glycoprotein. We also found that when expressed in the MPC-11 variant cells, alpha heavy chains were glycosylated at a third, normally unused site.
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PMID:Selective removal of alpha heavy-chain glycosylation sites causes immunoglobulin A degradation and reduced secretion. 314 84

A rat hybridoma producing IgM monoclonal antibody (MAb) GP21:56 was generated with specificity for a high-molecular-weight, mucin-like glycoprotein (gp580) present on highly metastatic 13762NF rat mammary adenocarcinoma cells. The hybridoma was made by fusing rat Y3 Ag1.2.3 myeloma cells with spleen cells from a rat immunized i.d. with purified gp580. The gp580 appeared to be of low immunogenicity in syngeneic F344 rats because a total of 27 fusions were required to produce one hybridoma with specificity for this glycoprotein. Immunoblotting of purified gp580 after electrophoresis in 1% agarose and antibody-binding assays using purified gp580 linked to microtiter plates confirmed that MAb GP21:56 bound specifically to gp580. Other MAbs made against breast mucins were negative for gp580 reactivity. Enzyme-linked immunoabsorbent assays (ELISA) and radiolabelled antibody binding assays demonstrated that MAb GP21:56 bound to 13762NF adenocarcinoma cell lines and clones in relation to their spontaneous metastatic potentials; significantly more MAb GP21:56 bound to highly metastatic MTLn3 cells than to low metastatic MTC cells, and MAb GP21:56 showed little reactivity towards the majority of other cell lines tested, whether of rodent or of human origin. Kinetic binding studies indicated that MAb GP21:56 does not have a high affinity for gp580 but, once bound, it shows high avidity for this sialogalactoprotein. Localization studies using frozen tissue sections of 13762NF tumors indicated that MAb GP21:56 reacts with tumor cells grown in vivo in an analogous manner to in vitro cultured cells. Using immunoperoxidase techniques, less than 50% of the highly metastatic MTLn3 tumor cells were stained, whereas approximately 20% of the intermediate metastatic MTF7 and MTLn2 cells and less than 10% of low metastatic MTC and MTPa cells were stained with MAb GP21:56. The cell-to-cell reactivity was heterogeneous and mainly associated with the tumor-cell surface and extracellular matrix.
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PMID:Development and characterization of a syngeneic monoclonal antibody to a rat mammary tumor metastasis-associated mucin-like cell-surface antigen (gp580). 317 31

Six interspecific hybridomas (heterohybridomas) secreting bovine monoclonal antibodies (MAbs) against respiratory syncytial (RS) virus were produced. Four of the heterohybridomas were formed using the mouse myeloma cell line NS1 as the fusion partner, one using NS0, and the remaining heterohybridoma was formed using a bovine X murine hybridoma as the fusion partner. Five heterohybridomas secreted bovine IgG1 and one secreted IgG2. All six MAbs recognized human subtype A and B viruses as well as bovine RS virus. They were specific for the fusion glycoprotein and reacted with a 140K dimer and a 70K monomer in a Western blot of native antigen; three also bound to the 46K F1 component and its 22K cleavage product in a blot of reduced antigen. Two of these MAbs neutralized RS virus infectivity, inhibited virus-induced fusion, lysed RS virus-infected cells in the presence of complement and protected mice against RS virus challenge.
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PMID:Production and characterization of bovine monoclonal antibodies to respiratory syncytial virus. 319 2

Monoclonal antibodies were raised reacting with placental protein 5 (PP5), a glycoprotein with properties of a serine protease inhibitor. Immunization was carried out with an antigen purified from late pregnancy placenta tissues. After fusion with myeloma cells, clones producing antibodies reacting with PP5 were isolated. Antibodies produced by two of the established hybridoma clones were characterized. The Ka of the antibodies was 0.22 x 10(9) L/mol and 0.3 x 10(8) L/mol. in Western blot analysis, both monoclonal antibodies reacted with the purified antigen that had a relative molecular weight (Mr) of 30 kd, but minor components of Mr 27 kd, 56 kd, and 62 kd were also identified. In polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate under reducing conditions, the purified protein yielded three polypeptides (Mrs of 16.4 kd, 16.8 kd, and 18.3 kd) that did not react with the monoclonal antibodies in Western blot analysis. By immunoperoxidase staining with monoclonal and polyclonal antibodies, PP5 was localized to the syncytiotrophoblast, cytotrophoblast, and endothelium of early and late pregnancy placenta tissues, whereas various other tissues were PP5-negative. In immunofluorescence staining, isolated endothelial cells were stained with both monoclonal antibodies. Endothelial cells in monolayer culture released into the medium a substance that is immunologically similar to purified PP5.
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PMID:Monoclonal antibodies reacting with placental protein 5: use in radioimmunoassay, Western blot analysis, and immunohistochemistry. 327 2

In an attempt to raise monoclonal antibodies to chicken pituitary glycoprotein hormones, mice were immunized with the concanavalin A-adsorbed components of a hypophyseal extract. Fusions of these spleen cells with myeloma cells repeatedly yielded hybridoma lines secreting antibodies that recognized specifically the pituitary caudal acidophils, known as the somatotropes. This paper reveals the existence of a glycosylated counterpart of the well-established holoprotein form of chicken growth hormone, similar to what has been established for human growth hormone and prolactin.
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PMID:Glycosylated chicken growth hormone. 343 15

The murine BALB/c myeloma LPC-1 demonstrates a periodic resistance to lysis by immune mechanisms; this correlates with the production and accumulation of a trypsin-sensitive, single chain glycoprotein of 160 kilodaltons gp160 on the tumor cell surface. Tumor cells obtained 4 days after transplantation are lysed by cytotoxic T lymphocytes whereas ten-day cells are resistant to lysis. The progressive resistance to lysis was correlated with an increasing amount of gp160 on the surface of LPC-1 cells. Cell surface morphology, as determined by scanning electron microscopy, showed that early cells consisted of equal proportions of cells having microvilli or ruffles. The late cell population consisted mainly of cells with microvilli. These microvilli were twice as abundant on late LPC-1 cells as on early cells. Transmission electron microscopy images of late LPC-1 cells suggested an active protein synthesis which correlated with a more intense deposition of ruthenium red and an increasing amount of gp160 on the cell surface.
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PMID:Morphology surface of a mouse plasmacytoma (LPC-1) showing cyclic resistance to immune lysis. 348 27


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