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)

Inclusions in the nucleus, compared with those in the cytoplasm, are rare in myeloma cells but have been reported in all electrophoretic varieties of multiple myeloma except the nonsecretory type. In this unusual case, a 54 year old Chinese woman had a pathological fracture of the left femur, and biopsy of the fracture site revealed a round cell tumor compatible with plasmacytoma. A bone marrow aspirate revealed 50% plasma cells, many of which contained intranuclear inclusions. Protein electrophoresis was normal with no paraprotein, and urine was free from Bence-Jones protein. Under electron microscopy, the plasma cells showed electron-dense spherules not circumscribed by a membrane. The absence of a membrane was unusual, because according to all reported cases, these intranuclear inclusions were invariably membrane-bound. The association of nonsecretion of paraprotein in myeloma, which is rare, and the absence of a membrane enclosing the intranuclear inclusions, which is heretofore unreported, is probably not coincidental but causally related in that paraprotein produced in the nucleus of myeloma cells (stored in the form of intranuclear inclusions) fails to be detected in serum and urine because of noninteraction between these inclusions and the membranes of the nucleus and endoplasmic reticulum.
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PMID:Intranuclear inclusions in myeloma cells in a case of nonsecretory multiple myeloma. 217 3

Two classes of immunoglobulin, IgM and IgD, are present as antigen receptors on the surface of mature B lymphocytes. We show here that IgD molecules are noncovalently associated in the B cell membrane with a heterodimer consisting of two proteins of 35 kd (IgD-alpha) and 39 kd (Ig-beta), respectively. The two novel proteins are not found in the IgD-expressing myeloma J558L delta m, which fails to bring IgD antigen receptor onto the cell surface. In a surface IgD positive variant line of this myeloma, however, membrane-bound IgD molecules are associated with the heterodimer, suggesting that the formation of an antigen receptor complex is required for surface IgD expression. We further demonstrate that the IgD-associated heterodimer differs partly from that of the IgM antigen receptor and that its binding to the heavy chain only requires the presence of the last constant domain and the transmembrane part of the delta m chain.
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PMID:Molecular components of the B cell antigen receptor complex of class IgD differ partly from those of IgM. 230 36

Immunoglobulin E (IgE) has a central role in allergic reactions although it rarely exceeds 5 micrograms ml-1 even in the serum of severely allergic individuals. Both mast cells and basophils possess receptors which bind the Fc portion of IgE with high affinity; crosslinking of membrane-bound IgE by allergen results in degranulation of the cell and release of a variety of pharmacologically active mediator including histamine. Myeloma IgE has been successfully used to block the skin sensitizing activity of allergic sera; however, human myeloma IgE is clearly in limited supply. The emergence of techniques allowing the stable introduction of immunoglobulin gene DNA into myeloma cells has allowed us to construct a mouse cell line that secretes a chimaeric IgE, lambda 1 antibody whose heavy chain is composed of a human C epsilon constant region fused to a mouse variable (VH) region. This chimaeric IgE is specific for the hapten 4-hydroxy-3-nitro-phenacetyl (NP) and can, when crosslinked by antigen, trigger the degranulation of human basophils. When not crosslinked, however, the chimaeric IgE can prevent the passive sensitization of these cells by sera from allergic subjects.
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PMID:A hapten-specific chimaeric IgE antibody with human physiological effector function. 258 Feb 39

N-Glycolylneuraminic acid (Neu5Gc) is an oncofetal antigen in humans and is developmentally regulated in rodents. We have explored the biology of N-acetylneuraminic acid hydroxylase, the enzyme responsible for conversion of the parent sialic acid, N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. We show that the major sialic acid in all compartments of murine myeloma cell lines is Neu5Gc. Pulse-chase analysis in these cells with the sialic acid precursor [6-3H]N-acetylmannosamine demonstrates that most of the newly synthesized Neu5Gc appears initially in the cytosolic low-molecular weight pool bound to CMP. The percentage of Neu5Gc on membrane-bound sialic acids closely parallels that in the CMP-bound pool at various times of chase, whereas that in the free sialic acid pool is very low initially, and rises only later during the chase. This implies that conversion from Neu5Ac to Neu5Gc occurs primarily while Neu5Ac is in its sugar nucleotide form. In support of this, the hydroxylase enzyme from a variety of tissues and cells converted CMP-Neu5Ac to CMP-Neu5Gc, but showed no activity towards free or alpha-glycosidically bound Neu5Ac. Furthermore, the majority of the enzyme activity is found in the cytosol. Studies with isolated intact Golgi vesicles indicate that CMP-Neu5Gc can be transported and utilized for transfer of Neu5Gc to glycoconjugates. The general properties of the enzyme have also been investigated. The Km for CMP-Neu5Ac is in the range of 0.6-2.5 microM. No activity can be detected against the beta-methylglycoside of Neu5Ac. On the other hand, inhibition studies suggest that the enzyme recognizes both the 5'-phosphate group and the pyrimidine base of the substrate. Taken together, the data allow us to propose pathways for the biosynthesis and reutilization of Neu5Gc, with initial conversion from Neu5Ac occurring primarily at the level of the sugar nucleotide. Subsequent release and reutilization of Neu5Gc could then account for the higher steady-state level of Neu5Gc found in all of the sialic acid pools of the cell.
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PMID:Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool. 268 73

Affinity-purified lactogenic receptors from female rat liver microsomal membranes were used to raise antibodies in female Balb/c mice. Mouse spleen and myeloma cells were fused and hybridoma-derived monoclonal antibodies (Mabs) were produced by in-vitro cell culture. Mab from a selected clone was sequentially purified by chromatography on a thiophilic gel and on agarose-bound protein A. The Mab was found to be of IgG1 subclass and of kappa type. The Mab recognized membrane-bound and solubilized (by the detergent heptaoxyethylene lauryl ether; G3707) receptors as well as receptors purified by affinity chromatography and subsequent sodium dodecyl sulphate (SDS) electrophoresis from female rat liver. The Mab bound to receptors from several other female rat tissues, such as ovary, kidney and adrenal, whereas there was no binding to liver receptors from cow and rabbit. Displacement experiments showed that the Mab was specific for a lactogenic type of receptor, in agreement with the finding that the Mab did not recognize receptors from male rat liver. The Mab also bound to cytoplasmic receptors (present in the supernatant after centrifugation at 100,000 g) from female rat liver, suggesting a structural similarity between the cytoplasmic and the microsomal receptors. Analysis of purified receptors by SDS electrophoresis and subsequent Western blot with 125I-labelled Mab as a probe showed one band corresponding to an Mr of 45,500 +/- 2500 (n = 5). The same band was obtained with 125I-labelled human GH, showing that the Mab binds to the unit which accommodates the hormone-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A monoclonal antibody to lactogenic receptors from female rat liver. 292 9

An autopsy case of multiple myeloma, IgA kappa type, accompanying systemic crystal-storing histiocytosis and generalized amyloidosis, is reported. Besides multiple destructive lesions in the skeletal bones, nodular myeloma cell infiltrates were scattered in the liver, spleen, and both kidneys. Not only in these lesions but also in the reticuloendothelial organs, crystal-storing macrophages appeared dispersively or in clusters. Electron microscopically, numerous crystalline inclusions contained in the cytoplasm of macrophages were membrane-bound and of variable configuration, comprising of a homogeneous electron-lucid material. Enzyme cytochemically, almost all of the inclusions showed acid phosphatase activity. On the basis of the results obtained from the immunohistochemical, immunofluorescent and immunoelectron microscopic studies, it was considered that the crystalline inclusions stored in the macrophages were derived from IgA kappa immunoglobulin secreted from the myeloma cells and were formed within secondary lysosomes by crystallization during lysosomal digestion and degradation of the ingested immunoglobulin by macrophages. Generalized amyloidosis developed in different sites from those of the crystal-storing histiocytosis and were proven immunohistochemically to belong to AL amyloidosis probably derived from a certain group of A kappa precursor protein.
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PMID:Multiple myeloma, IgA kappa type, accompanying crystal-storing histiocytosis and amyloidosis. 303 87

In the present study the in vitro binding, internalization and degradation of IgA immune complexes (IC) by phagocytes was studied. As a model for IgA IC, heat-aggregated human secretory IgA (AsIgA) was prepared and resident rat peritoneal macrophages (PM phi) were used as a source of phagocytes. First, binding of 125I-AsIgA to rat PM phi was investigated. Binding of 125I-AsIgA to PM phi at 4 degrees was saturable and reached plateau values after 2 hr. At 37 degrees, degradation of membrane-bound 125I-AsIgA into trichloroacetic acid (TCA)-soluble fragments occurred. Parallel experiments with unlabelled AsIgA and 125I-labelled anti-human IgA revealed that degradation of AsIgA was preceded by internalization of AsIgA. The specificity of binding of 125I-AsIgA to PM phi was investigated using human IgG, human serum IgA, human myeloma IgA1, human sIgA and the glycoproteins asialofetuin and ovalbumin. The binding of 125I-AsIgA to rat PM phi was inhibited in the presence of sIgA and asialofetuin. In contrast IgG and ovalbumin had no effect. These results suggest that receptors with a specificity for galactose on the rat PM phi are involved in the binding of AsIgA.
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PMID:Binding, internalization and degradation of soluble aggregates of human secretory IgA by resident rat peritoneal macrophages. 316 44

Expression vectors coding for membrane-bound IgM antibodies were introduced into myeloma and B lymphoma cells. Only the lymphoma but not the myeloma cells were able to express the antibodies on the cell surface, although in both cases, complete antibodies were assembled intracellularly. In myeloma cells, the Ig molecules did not reach the Golgi compartment. Thus, the intracellular transport of membrane-bound antibodies is controlled in the B cell lineages in a developmentally ordered fashion.
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PMID:Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface. 325 11

The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.
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PMID:Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals. 397 48

The preparation, properties, and some applications of ferritin conjugates of two plant agglutinins, concanavalin A and Ricinus communis agglutinin, are reported. These conjugates serve as specific electron-dense stains for cell- and membrane-bound saccharide residues of the alpha-D-mannopyranosyl and beta-D-galactopyranosyl configurations, respectively, and as examples of a wide range of ferritin-plant agglutinin conjugates useful as high resolution saccharide stains. By using a technique for preparing flattened membrane specimens, it was found with a variety of mammalian cell plasma membranes (lymphocyte, lymphoma, and myeloma and normal, spontaneously and virally transformed fibroblasts) that the ferritin conjugates were localized exclusively to the exterior face of the membrane, with essentially none found on the cytoplasmic face. On the exterior face the topographical distribution of ferritin conjugates appeared to be random. The asymmetrical distribution of saccharide residues to the outer membrane face can be explained by an "assembly line" process whereby new plasma membrane is made from intracellular precursor membranes. It also suggests that the saccharide-containing components of the plasma membrane do not rotate at any appreciable rate from one membrane surface to the other.
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PMID:The distribution and asymmetry of mammalian cell surface saccharides utilizing ferritin-conjugated plant agglutinins as specific saccharide stains. 412 77


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