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)

Immunoglobulin kappa-chain mRNA was hybridized with DNA in order to assess the kappa-gene frequency. Kappa-mRNA was purified from membrane-bound ribosomes of mouse myeloma MOPC-41 by poly (U) chromatography and isolation of a 13S RNA by successive sucrose density gradient centrifugations. The RNA coded for kappa-chain precursor molecules in cell-free protein synthesis and essentially no other proteins. MOPC-41 kappa-mRNA hybridized with MOPC-41, MPC-11, and Krebs DNA with the same kinetics: the majority of the hybrids was formed with rare or unique DNA sequences (Cot/2 450 to 900), a small portion with highly repetitive sequences (Cot/2 5--6). The slow hybrids were well matched and the rapid hybrids were mismatched by about 4%, regardless of the DNA used. It was further investigated whether the rapid hybrids contained translatable kappa-mRNA or were due to impurities in the RNA preparations. Kappa-mRNA and globin-mRNA (as an internal standard for a unique transcript) were hybridized with DNA to Cot 20 or 48, the hybridized and unhybridized RNA were isolated by hydroxyopatite-urea chromatography and, after removal of the DNA, translated in a cell-free system. The cell-free products were analyzed by SDS-polyacrylamide gel electrophoresis and immunoprecipitation. It was found that approximately equal quantities of translatable kappa- and globin-mRNA were hybridized maximally 1.7%). The results do not support the hypothesis that kappa-mRNA is a transcript of both repetitive and unique DNA sequences.
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PMID:Analysis of immunoglobulin genes: DNA/RNA hybridization with immunoglobulin kappa-chain mRNA and isolation and translation of hybridized RNA. 81 83

The ultrastructure of intercellular connections between plasma cells and dendritic bone marrow macrophages found in bone marrow aspirations from 15 patients with multiple myeloma is described. Two types of cell-to-cell contact were observed: 1) a juxtaposed type and 2) a mortise-joint type. In both types the zones are characterized by an amorphous electron dense layer adherent to the inner leaflet of the cytoplasmic membrane of the plasma cell, whereas no morphological changes are present in the macrophage. The thickness of the electron dense layer in the plasma cell was found to range from 11 to 33 nm and its extension along the membrane fron 0.2 micronm to 2--3 micronm. The distance from plasma cell surface to the surface of the macrophage was found to range from 11 to 27 nm, but the two cell membranes were always parallel at the contact zone region. At the contact zones small amounts of electron dense material were generally present in the interspace between the cells, and sometimes fine bridges of this material were seen to connect the two cells. The cytoplasm of the plasma cell was sparse in organelles at the contact zone region except for cytoplasmic filaments (7--9 nm in diameter). However, more than 50 per cent of the plasma cells did show a few electron dense, membrane-bound granules close to the contact zones. In some plasma cells a few coated vesicles were also found adjacent to the dense layers of the contact zones.
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PMID:The ultrastructure of contact zones between plasma cells and macrophages in the bone marrow of patients with multiple myeloma. 87 72

A 54-year-old man with acinic cell adenocarcinoma of the pancreas died of oliguric renal failure associated with myeloma-like renal lesions. Electron microscopical study of the tumor cells disclosed rich rough-surfaced endoplasmic reticulum and membrane-bound secretory granules, which indicated active protein synthesis and suggested that abnormal proteins produced by the tumor cells were the underlying cause of the renal lesions. Rapid deterioration of renal function ensued after intravenous pyelography, as is usual in the syndrome of myeloma-like lesions of the kidneys. This case presents further evidence for the occurrence of "myeloma kidney" in association with tumors other than plasma cell myeloma.
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PMID:Myeloma-like lesions of the kidney. Occurrence in a case of acinic cell adenocarcinoma of the pancreas. 98 91

Translation of total polysomal RNA from sarcoma 180 ascites cells in a wheat germ cell-free system produces two major polypeptides, A and B, with molecular weights of 50,000 and 45,000, respectively. Fractionation on Millipore filters or on oligo(dT)-cellulose leads to retention of the mRNA specific for protein A in the poly(A)-containing fraction and to accumulation of the B mRNA in the unadsorbed poly(A)-deficient fraction. The mRNA for B sediments at approximately 18 S; it is released as a 50S ribonucleorprotein upon EDTA treatment of polysomes. Its translation is particularly sensitive to an inhibitor present in the polysomal RNA. The poly(A)-deficient mRNA for the 45,000 dalton polypeptide is also present in mouse myeloma MPC-11 cells, where it seems to be localized in membrane-bound polysomes.
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PMID:A major species of mammalian messenger RNA lacking a polyadenylate segment. 106 3

Soluble forms of the interleukin (IL)-2, IL-4 and IL-7 receptors which lack the transmembrane domain have been described. IL-6 is a growth factor important in the final differentiation of B-cells into plasma cells and in the pathogenesis of multiple myeloma. To determine whether the receptor for IL-6 may exist as a soluble molecule, RNA was analysed from the transformed B-cell lines U266, CESS and Daudi, from bone marrow from two myeloma patients, and from normal leukocytes. Using polymerase chain reaction, oligonucleotide primers which flank the transmembrane domain were selected to generate a 339 bp fragment. All samples produced equivalent amounts of the expected 339 bp fragment plus a smaller 245 bp fragment except Daudi which exhibited virtual absence of both. Sequence analysis of the smaller fragments from each of the five samples demonstrated the deletion of the entire transmembrane region from codons 356 (G-TG) to 387 (AG-G). The boundaries of this deletion were identical in all cases. Partial sequence analysis of the ligand-binding domain for U266 demonstrated identical sequences for the membrane-bound and soluble forms of the IL-6 receptor cDNAs. In summary, an mRNA which encodes a soluble form of the IL-6 receptor is expressed in both normal and myeloma cells.
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PMID:Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. 163 65

The extracellular domain of the 55-kDa TNF receptor (rsTNFR beta) has been expressed as a secreted protein in baculovirus-infected insect cells and Chinese hamster ovary (CHO)/dhfr- cells. A chimeric fusion protein (rsTNFR beta-h gamma 3) constructed by inserting the extracellular part of the receptor in front of the hinge region of the human IgG C gamma 3 chain has been expressed in mouse myeloma cells. The recombinant receptor proteins were purified from transfected cell culture supernatants by TNF alpha- or protein G affinity chromatography and gel filtration. In a solid phase binding assay rsTNFR beta was found to bind TNF alpha with high affinity comparable with the membrane-bound full-length receptor. The affinity for TNF beta was slightly impaired. However, the bivalent rsTNFR beta-h gamma 3 fusion protein bound both ligands with a significantly higher affinity than monovalent rsTNFR beta reflecting most likely an increased avidity of the bivalent construct. A molecular mass of about 140 kDa for both rsTNFR beta.TNF alpha and rsTNFR beta.TNF beta complexes was determined in analytical ultracentrifugation studies strongly suggesting a stoichiometry of three rsTNFR beta molecules bound to one TNF alpha or TNF beta trimer. Sedimentation velocity and quasielastic light scattering measurements indicated an extended structure for rsTNFR beta and its TNF alpha and TNF beta complexes. Multiple receptor binding sites on TNF alpha trimers could also be demonstrated by a TNF alpha-induced agglutination of Latex beads coated with the rsTNFR beta-h gamma 3 fusion protein. Both rsTNFR beta and rsTNFR beta-h gamma 3 were found to inhibit binding of TNF alpha and TNF beta to native 55- and 75-kDa TNF receptors and to prevent TNF alpha and TNF beta bioactivity in a cellular cytotoxicity assay. Concentrations of rsTNFR beta-h gamma 3 equimolar to TNF alpha were sufficient to neutralize TNF activity almost completely, whereas a 10-100-fold excess of rsTNFR beta was needed for similar inhibitory effects. In view of their potent TNF antagonizing activity, recombinant soluble TNF receptor fragments might be useful as therapeutic agents in TNF-mediated disorders.
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PMID:Recombinant 55-kDa tumor necrosis factor (TNF) receptor. Stoichiometry of binding to TNF alpha and TNF beta and inhibition of TNF activity. 165 44

Certain species of histamine-releasing factor (HRF) have been demonstrated to distinguish a select group of allergic patients from healthy subjects. An IgE-dependent mechanism of action has been suggested. The donor and IgE dependency of HRF produced by peripheral blood mononuclear cells (PBMCs) has not been clearly demonstrated. In this study, we have compared the response of basophils from normal subjects versus allergic patients with and without asthma. In addition, we have addressed the IgE dependency of HRF recovered from cultures of PBMCs, T cells, B cells, macrophages, and bronchoalveolar lavage fluid. We have demonstrated that basophils from allergic as well as normal subjects respond to PBMC-HRF. The response of basophils from allergic patients with asthma is significantly increased. This heightened response to HRF does not correlate with the severity of disease as assessed by baseline spirometry, medication, and skin test scores. Stripping of the membrane-bound IgE by incubating basophils with lactic acid causes a significant loss of sensitivity to HRF generated by PBMCs, T cells, B cells, and macrophages, as well as to HRF recovered from bronchoalveolar fluid. The loss of response can be restored by sera from patients with asthma but not from normal subjects or by myeloma IgE. In addition, poorly responsive basophils from normal subjects can be rendered sensitive by incubating with sera from patients with asthma. The capacity of a given serum from a patient with asthma to restore the response to HRF is not correlated with the total concentration of IgE in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sensitivity of basophils to histamine releasing factor(s) of various origin: dependency on allergic phenotype of the donor and surface-bound IgE. 169 33

Because of the lack of a cell line expressing on surface and secreting human IgE of known Ag specificity, the construction of a transfectoma line possessing such properties would be useful for studying the roles of surface IgE and the effects of anti-IgE antibodies on IgE-producing B cells. Toward this goal, the human genomic DNA segment encompassing the two exons encoding the membrane anchor peptide of epsilon-chain and their flanking regions was sequenced. Hybrid epsilon and kappa genomic DNA comprising the C regions of human epsilon- and kappa-chains and the H and L chain V regions of the murine mAb BAT123, which reacts with the gp120 envelope protein of HIV-1, were constructed. Mammalian expression vectors containing these fusion genes were used to transfect murine myeloma Sp2/0 cells, and transfectants stably expressing on surface and secreting into culture medium chimeric IgE were obtained. The chimeric IgE showed identical Ag-binding properties as the murine mAb BAT123. Acting in concert with the specific peptide Ag polyvalently coupled to a protein carrier, the chimeric antibody could induce histamine release from human blood basophils. These results demonstrate the potential utility of the transfectoma cells and the chimeric IgE in studying the roles of membrane-bound IgE and effects of anti-IgE antibodies on IgE-producing B cells.
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PMID:Transfectomas expressing both secreted and membrane-bound forms of chimeric IgE with anti-viral specificity. 170 91

A monoclonal antibody termed as Br4 was prepared by a fusion of the myeloma P3 x 63-AG8-653 with spleen cells from BALB/c mice immunized with chick embryonic brain cells. Immunocytochemically, it reacts strongly with certain neurons in cerebral cortex, hippocampus, substantia nigra, and granular layer of cerebellum from rat brain but does not react with the white matter. A monoclonal antibody Br4 also reacts with primary cultured chick neurons, but not with cultured astrocytes. Western blots show that Br4 recognizes three proteins of 145,000, 108,000, and 97,000 molecular weight from the rat brain. The protein with molecular weight 145,000 (p145) and the protein with 97,000 molecular weight (p97) are essentially soluble; p145 is especially enriched in the synaptosomal soluble fraction. The protein with 108,000 molecular weight (p108) is found in both membrane-bound and soluble forms. Western blots show that among the tissues examined the three proteins are found most abundant in brain and especially enriched in the cerebral cortex and hippocampus. The Br4 antigens may be useful in identifying neuronal cell subpopulations in the central nervous system.
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PMID:Monoclonal antibody Br4 recognizes specific neuronal cell types. 171 25

Differentiated thyroid carcinoma synthetize and secrete thyroglobulin. During its biosynthesis this antigen becomes expressed in the microvilli-bearing surface of carcinoma cells. Attempts have been carried out to target, with specific antithyroglobulin antibodies, the membrane bound absorption thyroglobulin in cancer cells for in vivo diagnosis and therapy. In the serum of patients with autoimmune thyroid diseases a high concentration of antithyroglobulin antibodies is frequently found (1-3 mg/ml). Their purification by immunoabsorption and dissociation is hampered by a low recovery and partial denaturation. It has been recently reported that about 1% of sera from Hashimoto's thyroiditis bear in their electrophoretogram a "myeloma-like protein". In the present report we describe in the serum of a Hashimoto patient a myeloma-like IgG which is an antithyroglobulin autoantibody with restricted functional and structural properties. The serum concentration of this myeloma-like IgG was found to be 40 mg/ml with a capacity of 6.5 nM of human thyroglobulin/mg IgG. The light chain composition was determined to be mostly of the lambda type. The clonal analysis of this myeloma IgG carried out by isoelectrofocusing, immunoblotting and autoradiography resulted in the recognition of several distinct clones, two of which were prominent at pH 8.7 and 7.8. By this technique and in view of the high serum concentration of this myeloma-like IgG, single clones of antithyroglobulin autoantibody can be easily obtained in high yields and without denaturation from human serum. This reagent could offer an ideal immunovector to target membrane-bound thyroglobulin of cancer cells.
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PMID:Monoclonal autoantibody to thyroglobulin as a possible vector in immunodiagnosis and immunotherapy of differentiated thyroid cancer. 209 Jul 95


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