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)

Twelve C57BL/6J anti-B-1355S monoclonal antibodies (five IgM lambda and seven IgM kappa) were characterized immunochemically by binding and inhibition ELISA. All 12 were negative for the expression of the cross-reactive idiotype (IdX) of BALB/c mice, as expected from previous work; no kappa IdX+ antibodies have been reported and IdX- lambda class antibodies were observed in B-1355-Con A induced immune sera [Geckeler W., Blomberg B., dePreval D. and Cohn M. (1977) Cold Spring Harb. Symp. quant. Biol. 41, 743-748]. The antibodies studied bind to B-1355 coated plates and this binding is inhibited by B-1355 but not by dextrans B-512 (F) or B-742S; the latter two have no linear alpha (1----3; 1) linkages. The nomenclature of Jeanes is used [Jeanes A. (1986) Molec. Immun. 23, 999-1028]; alpha (1----3; 1) refers to glucosyl diose residues linked alpha (1----3) linearly. In the case of B-1355 these linear stretches alternate with alpha (1, 6) linkages and are non-contiguous; alpha (1----3; b) refers to the linkage at a branching residue, e.g., a 1,3,6 linked moiety. The IgM kappa class antibodies are not inhibited by nigerose or nigerantetraose, suggesting that they have binding site sizes which are unusually large for B-1355 specific antibodies. The five IgM lambda antibodies are inhibited identically by equimolar amounts of nigerose and nigerantetraose, suggesting that their binding sites accommodate a disaccharide epitope. These antibodies are also inhibited by the alpha (1----6), alpha (1----4) triose, panose. The kappa class antibodies do not bind to alpha (1----3)-diglucosyl-(nigerosyl; N)-BSA. Four of the five lambda class antibodies show weak binding to N-BSA, while the fifth binds N-BSA better but less well than MOPC 104E (the BALB/c myeloma protein). All 12 antibodies are unique when compared to BALB/c antibodies derived from B-1355 immunization. The primary response of 15 C57BL/6J mice to B-1355 was re-assessed for kappa and lambda class antibody contribution. A patchy lambda class response was observed suggesting that previous lambda class responses may have been overlooked.
Mol Immunol 1989 Apr
PMID:Immunochemical analyses of C57BL/6J monoclonal anti-alpha (1----3) dextran antibodies. 246 48

In the present work, using an immunological approach, we have investigated the existence of common epitopes between two receptors of the glycoprotein hormone family, lutropin (LH) and thyrotropin (TSH) receptors. We have immunized high responder mice with purified porcine LH receptors obtained by successive affinity chromatographies on agarose-human chorionic gonadotropin (hCG) gels. From one fusion of splenocytes with the murine myeloma NSC1, secreting hybridomas were tested for their anti-LH receptor specificities. During sequential selection for this activity including direct recognition of the purified LH receptors in dot-blot assays and displacement experiments of 125I-pLH and 125I-hCG binding to different sources of receptors, we performed a parallel investigation of their anti-porcine TSH receptor activities. Purified immunoglobulins from two of them showed a TSH-like activity on the iodide metabolism of porcine thyroid cell, this activity being related to the phosphoinositide breakdown pathway; moreover, these antibodies obtained after immunization with porcine LH receptors were able to immunopurify human TSH receptors. The double selection process led us to characterize three groups of immunoglobulins: exclusive specificities for lutropin receptors or thyrotropin receptors and cross-reactive specificities. Our results demonstrate the possibility of sequence homologies at the protein and the gene levels between the receptors for the glycoprotein hormone family supporting the hypothesis of a common origin in evolution.
Mol Cell Endocrinol 1989 Aug
PMID:Lutropin receptor and thyrotropin receptor share a common epitope. 247 48

Both dextran B-1355 and nigerosyl-KLH (N-KLH) contain alpha(1----3) diglucosyl moieties and both induce lambda class serum antibodies which recognize the alpha(1----3) linkage. However, as shown here, some of the antibodies induced by the thymus-dependent form, N-KLH, have a distinct fine specificity. It is known that B-1355 induces antibodies which resemble the anti-alpha(1----3) myeloma proteins MOPC 104E and J558. The new fine specificity which does not resemble such antibodies is found in the serum of N-KLH primed mice challenged with N-KLH. The two fine specificity types are distinguished by their sensitivity to inhibition by nigerose in ELISA using B-1355 or N-BSA as bound antigen. Twelve hybridomas were produced from N-KLH primed mice boosted with either N-KLH or B-1355. Six of the 12 had the new fine specificity; only two out of the 12 expressed the IdX determinant commonly associated with the B-1355 response and neither of these possessed the new reactivity pattern. Comparative inhibition with the disaccharide nigerose and the tetrasaccharide nigerantetraose indicated that 11 out of the 12 hybridoma proteins have combining sites larger than a disaccharide. Southern and Northern blot analysis of eight hybridomas revealed that all expressed VH genes from the J558 family, but that at least two distinct VH genes from this family were used. The data support the hypothesis that immunization with an alpha(1----3) diglucosyl-protein conjugate alters the composition of the B cell pool capable of producing lambda class antibodies from that ordinarily observed following immunization with B-1355.
Mol Immunol 1989 Sep
PMID:Characterization of lambda class antibodies from the BALB/c memory response to a [glucosyl-alpha(1----3) glucosyl]-protein conjugate. 248 Dec 31

Ten different monoclonal antibody (monAB) preparations reacting with human IgL chains of the kappa type have been obtained. Nine of the monAB interacted with the kappa-chain C domain, whereas only one monAB reacted with the V domain. It has been determined that monAB against the C domain react with three different epitopes. One epitope is expressed on intact Ig molecules as well as on isolated kappa-chains, whereas the other two epitopes are found only on isolated kappa-chains. The expression of these epitopes in 40 different myeloma kappa-chain preparations belonging to four various subgroups was studied. The level of this C domain epitope expression has been shown to depend on the variable subgroups of kappa-chains indicating a close association between V and C domains. This association leads to the alteration of antigenic activity of some C domain epitopes. The alterations are thought to be local because, as a rule, they involve only one of the three epitopes.
Mol Biol (Mosk)
PMID:[Antigenic determinants of the constant region of human immunoglobin kappa-chain detected by monoclonal antibodies]. 248 11

Fusion between the thioguanine resistant myeloma cell line MOPC-315 [which produces alpha, lambda-2 antibodies specific to the 2,4-dinitrophenyl (DNP) hapten] and a long term in vivo maintained hybridoma 6100.15 [which produces mu, lambda-1 antibodies specific to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten] resulted in the generation of 12 hybridomas. These hybridomas secrete a mixed family of immunoglobulins (Ig) that bind both DNP and NP and express both IgM and IgA serological determinants. Affinity purified molecules from NP, DNP, anti-mu, or anti-alpha immunosorbents react with both anti-mu and anti-alpha antisera, suggesting that these Ig represent IgM-IgA hybrid molecules. This conclusion was supported by idiotypic analyses. To determine the roles of individual immunoglobulin chains in determining antibody specificity this IgM-IgA hybridoma was used for immunoselection. Following lysis with specific anti-mu and anti-idiotype antibodies, an alpha+, mu- variant clone (A12) was identified, which secreted Ig that binds DNP but not NP. The DNP binding proteins were shown to express alpha, lambda-1 and lambda-2 chains. In contrast, the Ig which lack DNP binding activity only expressed alpha and lambda-1 determinants. The combined results demonstrate that the lambda-1 chain from 6100.15 hybridoma cannot replace lambda-2 of MOPC-315 for DNP binding activity. These data imply that these closely related lambda chains carry sites critical for antigen binding activity. An IgM-IgA hybridoma variant (MA2) which secretes Ig that binds to NP and DNP and expresses mu, alpha and lambda-2 chains was also characterized. This molecule lacked a lambda-1 chain. To determine if the Ig prepared with heterologous mu and lambda-2 chains had NP binding activity required immunoselection of a fourth clone (M2). M2 secretes homogeneous Ig bearing only mu and lambda-2 chains. In contrast to either parental Ig, the M2 antibody molecules express dual binding activity to both NP and DNP. Thus, critical amino acid substitutions in the MOPC-315 lambda-2 sequence are required for DNA binding specificity.
Mol Immunol 1989 Mar
PMID:Production and immunoselection of IgM-IgA hybridomas: preparing immunoglobulins with dual binding specificity. 249 37

Five murine A/J hybridomas (the 35-20 group) produce anti-digoxin antibodies that have homologous heavy and light chain immunoglobulin variable regions (VH and VL), yet differ from each other in fine specificity and affinity for digoxin and related cardiac glycosides [Mudgett-Hunter et al. Molec. Immun. 22, 477-488 (1985)]. To determine the origin of the VH and VL genes used in this set of hybridomas, the rearranged VH and VL genes from one of the 35-20 group hybridomas, 40-140, were cloned. The expressed V region, the leader exon and the 5' transcription control regions were sequenced. VH40-140 is a member of the VH36-60 gene family and has greater than 90% homology with several members of that family. A VH40-140 hybridization probe detected two members of the VH36-60 gene family not previously described. The VL40-140 region, a member of the Vk9 subgroup, is nearly identical to the Vk region used by the myeloma T1. Southern analysis with several restriction endonucleases and hybridization probes indicated that the 35-20 group hybridomas each use the same heavy and light chain variable region gene segments in the assembly of their expressed antibody genes. Functional rearranged antibody genes were detected with JH and VH heavy chain probes and with Jk and Vk light chain probes. The availability of the clones of the one heavy and the one light chain variable region gene segment used by the 35-20 hybridoma group will facilitate the use of in vitro mutagenesis in studies of the structural basis of fine specificity in the digoxin antigen-antibody system.
Mol Immunol 1989 Apr
PMID:Characterization of the heavy and light chain immunoglobulin variable region genes used in a set of anti-digoxin antibodies. 249 40

The 78,000-dalton glucose-regulated protein (GRP78) is a stress-inducible protein localized in the endoplasmic reticulum. It has been identified as the immunoglobulin heavy-chain-binding protein. We report here a high level of GRP78 expression in a B-cell myeloma line, NS-1, which produces only kappa light-chain proteins but is unable to secrete them. GRP78 transcription was enhanced in NS-1 cells, resulting in higher levels of GRP78 mRNA and protein than in non-immunoglobulin-producing cells. Furthermore, the nonsecreted light chains in NS-1 cells were found in specific association with GRP78. We hypothesize that in nonsecreting lymphoid cells, the presence of free, unassembled light chains in the endoplasmic reticulum could result in increased transcription of the GRP78 gene and that GRP78 can also bind to immunoglobulin light chains.
Mol Cell Biol 1989 May
PMID:Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1). 250 63

Hybrids formed from a myeloma cell line, NS1, and macrophages initially show myeloma properties but later, after loss of the parental macrophage genome and consequent loss of myeloma characteristics, express macrophage properties. Molecular studies demonstrated that macrophage properties in the hybridomas originate from the NS1 parental cells (M. Setoguchi, S. Yoshida, Y. Higuchi, S. Akizuki, and S. Yamamoto, Somatic Cell Mol. Genet. 14:427-438, 1988). In such hybrids, N-myc was activated by insertion of endogenous Moloney-like retrovirus sequences into mouse N-myc exon 3 when the hybrids gained macrophage properties. Interestingly, expression of N-myc took place in all aged hybrids. These results suggest that such unique insertional mutagenesis occurs in a regionally specific manner and that expression of N-myc may play a role in hematopoietic lineage conversion.
Mol Cell Biol 1989 Oct
PMID:Insertional activation of N-myc by endogenous Moloney-like murine retrovirus sequences in macrophage cell lines derived from myeloma cell line-macrophage hybrids. 255 95

A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing alpha-smooth muscle actin. In the normal adult bone marrow, stromal cells did not contain alpha-smooth muscle actin, whereas during fetal life, many alpha-smooth muscle actin-containing MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic carcinoma, Hodgkin's disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myelo-proliferative diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial reticular cells undergoing cytoskeletal remodeling in response to various stimuli.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Alpha-smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions. 257 Apr 90

The circular dichroism (CD) spectra of five myeloma and six hybridoma proteins specific for phosphocholine were measured in the 250-310-nm range. The effect on the CD spectra of adding phosphocholine was also examined. The five myeloma proteins all had distinctive native spectra and, except for M603 and W3207, unique changes occurred on ligand binding. The hybridomas were chosen as pairs from each of the three known families of phosphocholine-specific immunoglobulins. Those from the T15 or M603 families resembled the appropriate prototype. However, the proteins from the M167 family were all distinctively different in their CD properties. In particular, the hybridoma protein 101.6G6 showed large CD changes on hapten binding and values for the association constant for phosphocholine of 1.1 X 10(5) M-1 and of 5.8 X 10(2) M-1 for acetylcholine were obtained by CD spectrophotometric titration. The CD properties of the proteins are interpreted in the light of the sequence data so far available, including the possible role of the D-segment.
Mol Immunol 1985 Mar
PMID:The circular dichroism of phosphocholine-specific mouse hybridoma and myeloma proteins: unusual properties of the hybridoma protein 101.6G6. 258 46


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