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)

Spleen cells of Biozzi-HR mice immunized with human thyroglobulin (hTg) were fused with P3-X63-Ag8.653 mouse myeloma cells. Twenty monoclonal antibodies (MAbs) selected by an enzyme immunoassay (indirect ELISA) were produced, purified and characterized. The equilibrium association constant (Ka) of one of the MAbs, determined by Scatchard analysis of the ELISA data, was found to be 2 X 10(9) M-1; the Ka of the other MAb, estimated from titration curves by comparison with the aforementioned MAb, ranged from 8 X 10(9) M-1 to 6 X 10(7) M-1. The reaction between the MAb and hTg was not inhibited by thyroxin (T4), triiodothyronine (T3) and triiodothyropropionic acid (DT3). Species specificity of the MAb was studied using bovine and porcine Tgb. The topology of the MAb was investigated by competitive inhibition immunoassays. Seven distinct antigenic regions were identified.
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PMID:Production and characterization of monoclonal antibodies against human thyroglobulin. 241 47

A panel of monoclonal antibodies (mAbs) against human thyroglobulin (hTg) was obtained by somatic fusion of the nonsecreting myeloma cell line P3X66 Ag8/0 and spleen cells of Balb/c mice immunized with purified hTg. Antibody secreting clones were selected by solid phase enzyme immunoassay and analyzed for cross-reaction with Tg from several animal species. Twelve out of 15 mAbs cross-reacted with both rat and mouse Tg and 11 Mabs cross-reacted with bovine Tg. The cross-reaction with mouse Tg paralleled that of rat Tg, whereas discrete differences between the cross-reactivity patterns with bovine Tg were observed. Two clones secreted mAbs specific for hTg. We further characterized the mAbs and found that three mAbs recognized T4-containing determinants and one mAb reacted with both T4 and T3-containing determinants on the Tg molecule. The binding of the mAbs to hormonogenic determinants depended upon the thyroid hormone content of the molecule and the integrity of the three dimensional structure of Tg. One other mAb reacted with four peptides of CNBr-cleaved hTg, indicating the recognition of a repetitive determinant in the hTg molecule distinct from the hormonogenic regions.
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PMID:Monoclonal antibodies to human thyroglobulin as probes for thyroglobulin structure. 243 29

We studied the biochemical properties and the reactivity of 13 monoclonal anti-thyroglobulin antibodies, obtained by fusing P3 X 63 (8653) myeloma cells with spleen cells from CBA and C57BL/6 mice previously immunized with syngeneic thyroglobulin. We demonstrated that among the 13 anti-thyroglobulin monoclonal antibodies that we studied, each of them was specific for only syngeneic thyroglobulin, as each of them was able to cross-react with heterologous or xenogeneic thyroglobulin. Two major kinds of monoclonal antibodies were obtained: the first ones are able to block in vitro primary syngeneic sensitization and, moreover, they mutually compete for thyroglobulin binding; the second ones are not involved in this in vitro PSS and do not compete for binding to thyroglobulin. These results suggest that a defined particular epitope, borne by thyroglobulin and expressed on the thyroid epithelial cells, is responsible for in vitro primary syngeneic sensitization.
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PMID:Primary syngeneic sensitization on monolayers of thyroid epithelial cells. X. Inhibition of T-cell proliferative response by thyroglobulin-specific monoclonal antibodies. 243 39

Human monoclonal antibodies to human endocrine cells have been obtained following the generation of immunoglobulin-secreting interspecies lymphocyte hybridomas. Peripheral blood lymphocytes from an adult patient presenting with acute onset, Type I, diabetes mellitus were fused in vitro with mouse myeloma cells of the NS1 cell line. Initial selection of resulting hybridomas was made by their ability to proliferate in HAT medium. Those hybridomas secreting human immunoglobulins were identified by radioimmunoassay and, thereafter, cloned at frequent intervals to ensure continued antibody production. Human monoclonal antibodies selected in this manner are being employed to identify those epitopes which are common antigenic targets during initial stages of autoimmune-mediated diabetes mellitus and associated multiple endocrinopathies. Of these antibodies, one (HML 3.22) recognizes an epitope present on the human TSH receptor and a second (HML 3.21) identifies a component of thyroglobulin. The potential value of human monoclonal antibodies as probes for analyzing autoimmune-mediated endocrine diseases is discussed.
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PMID:Human monoclonal antibodies to thyroid antigens derived by hybridization of lymphocytes from a diabetic patient. 243 25

Two types of hybridomas secreting monoclonal antibodies (MAB) with neutralizing activity against human interferon-r (HuIFN-r) were obtained by somatic cell hybridization between mouse myeloma P3UI cells and spleen cells from BALB/c mice immunized with purified recombinant HuIFN-r and a conjugate of a synthetic amino-terminal peptide (residues 4-21) of HuIFN-r and bovine thyroglobulin. One of these MAB recognized the amino-terminal region (residues 4-21) of HuIFN-r, and the other recognized some region in the internal part (residues 22-130) of the molecule. These results suggest that another region, in addition to the amino-terminal region, contributed to the biological activity of rHuIFN-r. A combination of one of these MAB and a previously described MAB directed to the carboxyl-terminal region (residues 131-146) of HuIFN-r enables a quantitative and sensitive assay method of biologically active rHuIFN-r.
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PMID:Monoclonal antibodies to human interferon-gamma. II: Antibodies with neutralizing activity. 243 10

Four hybridoma clones (BKL1, BKL2, BKL5 and BKL6), secreting monoclonal antibodies against the decapeptide luteinizing hormone releasing hormone (LHRH), were obtained by the fusion of Sp 2/0-Ag14 myeloma cells with spleen cells of a Balb/k mouse immunized with a conjugate of thyroglobulin-LHRH. All four monoclonal antibodies belong to the IgG1 subclass. The antibodies cross-reacted in RIA from 9.3 to 21% with 4-10 LHRH and less than 1% with 7-10 LHRH, 1-3 LHRH and LHRH-OH; 4-6 LHRH showed no cross-reaction. A RIA based on the BKL2 antibody and able to detect 4 pg LHRH per tube was developed. An extract of rat hypothalamus was submitted to Sephadex G50 separation and a single peak of LHRH immunoreactivity corresponding to synthetic LHRH, was detected with the antibody BKL2. When this material was further analyzed by HPLC, we found that the major peak of immunoreactivity co-migrated with synthetic LHRH. The data shows that the antibodies should be useful tools for biochemical and physiological studies on LHRH.
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PMID:Characterization of high affinity monoclonal antibodies against the luteinizing hormone-releasing hormone. 244 91

A monoclonal antibody to alpha-human atrial natriuretic polypeptide (alpha-hANP), KY-ANP-I, has been produced by fusion of a nonproducing mouse myeloma cell line, X63-Ag8.653, with spleen cells from BALB/c mice immunized with synthetic alpha-hANP conjugated to bovine thyroglobulin using the carbodiimide coupling procedure. Hybridomas were screened for antibody production by radioimmunoassay using culture media and 125I-alpha-hANP. They were cloned by the limiting dilution technique, expanded in culture, and injected intraperitoneally into BALB/c mice. The obtained antibody belonged to the immunoglobulin G1 subclass. Analysis by a Scatchard plot revealed a high affinity for alpha-hANP, with an association constant of 3.1 x 10(10) M-1. With this monoclonal antibody, a specific radioimmunoassay for alpha-hANP has been established. The antibody in mouse ascites was available for radioimmunoassay at a final dilution of 1:10(6). Values of IC10 and IC50 in this radioimmunoassay were 3 and 30 fmol/tube, respectively. The radioimmunoassay showed a cross-reactivity of 0.9% with alpha-rat ANP. alpha-hANP-(8-22) and alpha-ANP-(1-6) exhibited less cross-reactivity than alpha-rat ANP on a molar basis. There was no cross-reaction with alpha-ANP-(17-28). Thus, the recognized epitope must be located in the N-terminal half of the ring structure of alpha-hANP including Met12 residue. This radioimmunoassay could detect gamma-hANP and beta-hANP as well as alpha-hANP. The monoclonal antibody was also useful for immunohistochemical studies. ANP-positive cells were finely stained in the human atrium using the avidin-biotin-peroxidase complex technique.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A monoclonal antibody to alpha-human atrial natriuretic polypeptide. 245 52

We report on the molecular characterization of the heavy (H) chain variable (V) region of two murine autoantibodies reacting with a conventional self antigen, thyroglobulin (Tg), originated from unimmunized/unstimulated neonatal mice (clone B10H2) and from an adult hyperimmunized mouse (clone 62), respectively. Serologically, both hybridoma antibodies express the same idiotype (Id). By cloning and sequencing we demonstrated that their VH regions are encoded by identical VDJ gene elements including the VD and DJ joints. This VH belongs to the VH 7183 gene family, the most 3'-end proximal family in the murine genome. The D segment is unique and only 50% similar to any murine D segment. The J segment utilized is germ-line JH4. The cloned DNA rearrangement was transfected into the J558L myeloma cells and the secreted antibody was found to express the reference Id on the H chain, hence proving that the productive VDJ rearrangement had been identified. These results show that a spontaneously arising and an antigen-induced autoantibody use an identical VDJ gene rearrangement and that after hyperimmunization somatic mutation did not occur. The significance of this finding with respect to ontogeny of the B cell repertoire is discussed.
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PMID:Molecular characterization of the VH region of murine autoantibodies from neonatal and adult BALB/c mice. 249 69

To produce a rat monoclonal antibody directed to rat CRF (rCRF), female Wistar rats were actively immunized with a rCRF-bovine thyroglobulin conjugate. Immunization resulted in the formation of CRF antibodies, as indicated by binding of [125I]iodo-rCRF and attenuation of the plasma corticosterone responses to ether stress. Rat spleen cells were fused with mouse myeloma P3 cells, and a hybridoma clone (PFU 83) was selected according to its capacity to bind [125I]iodo-rCRF and inhibit rCRF-induced ACTH release from cultured rat pituitary cells. PFU 83 antibodies (IgG2a subclass) are directed to the extreme C-terminal part (amino acids 38-39) of rCRF and bind with an affinity constant of 21 nM. In vitro, PFU 83 causes a parallel shift to the right of the rCRF dose-ACTH response curve, with an apparent affinity of 10 nM. PFU 83 neither binds nor blocks the ACTH-releasing activity of oCRF. Intravenous administration of PFU 83 ascites (generated in nude mice) to Wistar rats caused a dose-dependent inhibition of ether-induced ACTH secretion. Full blockade of the ACTH response to ether was found at a dose of 10 nmol PFU 83/rat. Based on the dynamics of rCRF binding and its in vitro and in vivo effects, we conclude that the rCRF-blocking bioactivity of PFU 83 is due to binding of PFU 83 to native rCRF and formation of a biologically inactive complex. Finally, we found that PFU 83 did not affect resting or ether-induced alpha MSH secretion, indicating that CRF does not play a major role in the control of alpha MSH secretion.
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PMID:Characterization and biological activity of a rat monoclonal antibody to rat/human corticotropin-releasing factor. 253 78

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.
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PMID:A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody. 256 81


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