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)

We have used nuclear run-on and DNase I sensitivity analyses to study the activity of the N-myc genes in cell lines that represent different stages of B-cell development. Both transformed pre-B-cell lines and a nontransformed pre-B-cell clone transcribe the N- and c-myc genes at substantial levels; in the nontransformed clone, transcription of these genes is regulated by the pre-B-cell growth factor interleukin-7. In contrast, transformed cell lines that represent the more mature stages of the B-cell pathway and mitogen-stimulated normal splenic B lymphocytes express the c-myc gene but do not express the N-myc gene at detectable levels. Down-regulation of N-myc expression in these cells occurs at the level of transcriptional initiation. Correspondingly, a set of DNase I-hypersensitive sites present in the 5' region of the N-myc promoter of pre-B-cell lines are absent in B-cell lines. To further elucidate this process, we have constructed fusion cell lines between an N-myc-expressing pre-B-cell line and a nonexpressing myeloma line; the hybrid cell lines transcriptionally down-regulate the pre-B copies of the N-myc gene. Lack of N-myc expression in a number of nonlymphoid cell lines also resulted from lack of N-myc transcription. Together, our findings demonstrate that the down-regulation of N-myc expression in the later stages of B-cell development is mediated primarily at the level of transcriptional initiation. They further show that dominant, trans-acting factors present in more mature B-lineage cell lines act to down-regulate the transcription of N-myc.
Mol Cell Biol 1992 Apr
PMID:Transcriptional down-regulation of N-myc expression during B-cell development. 154 13

Human IgA occurs in body fluids as monomers, dimers and secretory IgA (sIgA). Besides the cysteine residues in intra-domain, inter-chain and inter-subunit disulfide bonds IgA molecules contain several cysteine residues with unknown function and reactivity. Limited reductions on serum IgA1 and secretory IgA1 with glutathione revealed that four cysteine residues per monomer or subunit were part of labile bonds. Six cysteine residues were reduced in F(ab')2 fragments and about three in Fc fragments, but none in Fab fragments, indicating that the labile bonds occur in the Fc fragment. By SDS-PAGE analyses of reduced proteins labile inter-alpha chain bond(s) were detected in F(ab')2 and F(abc)2 fragments but not in Fc fragments and intact IgA1, thus showing the importance of the CH3 domains for the structural stability of the hinge region. Nine cysteine residues per IgA1 were reduced with 0.01 M DTT and a large proportion of the IgA1 myeloma proteins formed half-molecules consisting of an alpha- and a light chain, but sIgA1 remained intact. This indicates a relative stability of heavy to light chain and inter-subunit bonds. Reductions in the presence of 2% SDS disrupted several intra-chain bonds. Binding studies with (CH2)2-specific monoclonal antibodies, which detect an epitope expressed only on IgA molecules with disulfide linked alpha chains, were in accordance with the SDS-PAGE results. A new model for the location of labile and more stable disulfide bonds is discussed.
Mol Immunol 1992 Mar
PMID:Effects of limited reduction on disulfide bonds in human IgA1 and IgA1 fragments. 155 43

Nine monoclonals against human Ig lambda chains were produced, 4 antibodies react with C-domain, 5--with V-domain of the lambda chain. Anti-C lambda domain antibodies recognize not less than 3 epitopes and one of them is expressed only on the isolated chain. Anti-V lambda antibodies bind both isolated lambda chain and intact IgG, IgM, IgA. Four epitopes are expressed by few lambda Bence Jones proteins of the III subgroup, the immunogen possessing the same isotype. The 4 mentioned epitopes represent private idiotypic determinants. The epitope 3E10 is characteristic of 50% Bence Jones proteins of the II and III V lambda-subgroups thus representing a common idiotypic determinant. Using anti-V lambda antibodies germ line variability of V lambda III proteins was analysed and the similarity of antigenic structure of normal and myeloma human Ig lambda chains was demonstrated.
Mol Biol (Mosk)
PMID:[Study of the antigenic structure of human immunoglobulin lambda-chain using monoclonal antibodies]. 169 12

The ultrastructural localization of RNA in myeloma cells was studied by the RNase-gold method. Gold particles indicating the presence of RNA were observed in large numbers, particularly in the granular component of the nucleolus and periphery of the rough endoplasmic reticulum, but not in the Golgi area, mitochondria, intranuclear inclusion bodies, cytoplasmic inclusion bodies, dense bodies, or cisternae of the rough endoplasmic reticulum. In the nuclear chromatin and nucleolus, gold particles were more numerous as these structures were less mature. They were found in larger numbers also in the cytoplasm of immature cells. In plasma cells from patients with macroglobulinemia, gold particles were fewer than in myeloma cells of multiple myeloma, but there was no difference in their distribution pattern.
Exp Mol Pathol 1990 Jun
PMID:Fine structural localization of RNA in myeloma cells detected by the enzyme-gold method. 169 57

Two monoclonal IgG3 syngeneic anti-idiotypes are described which form soluble and insoluble complexes with anti-alpha(1----6)dextran hybridoma and myeloma proteins. Specific precipitation was seen when purified anti-alpha(1----6)dextrans were added to ascitic fluid containing IgG3 kappa anti-idiotype. Analysis of the supernatants of the idiotype-anti-idiotype precipitates demonstrated the presence of soluble complexes whose mobilities in polyacrylamide gels could, in some cases, be distinguished from that of free anti-idiotype. An IgG1 kappa anti-idiotype is described which did not form precipitates with anti-alpha(1----6)dextrans unless 3% PEG 6000 was added.
Mol Immunol 1990 Jun
PMID:An immunochemical analysis of precipitating and non-precipitating idiotype-anti-idiotype reactions. 169 51

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.
Mol Cell Biol 1990 Dec
PMID:Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. 170 Oct 20

We have characterized a monoclonal isogeneic antiidiotype, IdB5.7, from a BALB/c mouse immunized with the anti-alpha(1----6)dextran C57BL/6 45.21.1. It defined a hapten-inhibitable idiotope expressed on four of the 2 myeloma and 37 hybridoma anti-alpha(1----6)dextrans tested. Sequence comparison of Id+ and Id- anti-alpha(1----6)dextrans suggested that two extra amino acids at VH 100A and 100B and different residues at VH 101 abolish the expression of the idiotope in the Id- anti-alpha(1----6)dextrans. Sequence analysis of the VH of IdB5.7 showed a CDR1 longer than usual and a D segment in CDR3 formed by the fusion of two D minigenes. The IdB5.7 V kappa uses the V kappa 1 germline gene K5.1 with a few substitutions. The D-D fusion in VH CDR3 is a feature which has been reported in several other antiidiotypic antibodies.
Mol Immunol
PMID:Specificity and variable region cDNA sequence of an isogeneic monoclonal antiidiotype to an anti-alpha(1----6)dextran. 171 74

Twelve monoclonal antibodies (mAb) were isolated that bound to six clusters of epitopes on the constant region of the epsilon chain of human IgE. Four of the mAb bound to the C epsilon 1 or early C epsilon 2 regions; three of these bound to the IgE myeloma protein PS and to serum IgE but not to the IgE myeloma protein ND. These mAb probably recognize an allotypic marker. Another mAb reacted with heat-denatured, but not native IgE. Four of the mAb failed to release histamine; the epitopes recognized by these mAb are in the C epsilon 1, C epsilon 2 and C epsilon 3-4 regions of IgE. Three of these non-histamine releasing mAb did not bind to IgE on the basophil surface. These mAb recognize epitopes in C epsilon 2 and C epsilon 3-4 that are not accessible when IgE is bound to its receptor. Four mAb inhibited IgE binding to basophils; two of these did not release histamine, and two others that bind to epitopes in the C epsilon 2-4 domain, released histamine and therefore blocked IgE binding by steric hindrance. Inhibition of IgE binding by different mAb suggest that the Fc epsilon RI and Fc epsilon RII bind to partly overlapping regions of the IgE molecule although the sites do not appear to be identical. A number of sites on C epsilon 1 and C epsilon 3-4 were accessible when IgE is bound to its basophil receptor. The data support the concept that only part of the Fc portion of IgE is hidden in the receptor and that portions of C epsilon 1-4 are accessible on the cell surface. These mAb should be useful in determining the domains of IgE that are critical for its biological activity.
Mol Immunol 1991 Jun
PMID:Monoclonal antibodies defining epitopes on human IgE. 171 47

BCA200 has been described as a 200,000 Mr monomeric cell surface glycoprotein associated with human breast cancer. Since the physical properties and cellular distribution of BCA200 resemble those of c-erbB-2, antibodies to BCA200 were tested for the ability to bind a recombinant protein containing the c-erbB-2 extracellular domain (erbB-2 ECD). Three antibodies to distinct epitopes of BCA200 reacted with erbB-2 ECD but not with a control protein expressed in a similar baculovirus lysate. Control myeloma proteins and antibodies to four other antigens did not react with erbB-2 ECD. A protein with the expected molecular weight for erbB-2 ECD was also immunoprecipitated by anti-BCA200 antibody 520C9. We conclude that BCA200 is another synonym for c-erbB-2.
Mol Immunol 1991 Aug
PMID:Identity of BCA200 and c-erbB-2 indicated by reactivity of monoclonal antibodies with recombinant c-erbB-2. 171 33

To investigate the IL-6/IL-6 receptor system, we obtained five murine monoclonal antibodies against human IL-6, which neutralize its biological activity. We classified them into two groups (Type I mAb and Type II mAb) according to the epitopes they recognized. These two types of antibodies showed no difference in the manner in which they neutralized IL-6 activity, but they differed in the way they inhibited the binding of IL-6 to its receptor. While Type I mAb inhibited IL-6 binding to its receptor completely, Type II mAb inhibited only partially, even at a concn of Type II mAb sufficient to neutralize biological activity. Scatchard plot analysis revealed that in the case of the human myeloma cell line, the U266 cell, which showed two-phase binding of IL-6 to its receptor, the high affinity binding disappeared and the affinity of the low affinity binding decreased in the presence of Type II mAb. These results suggest that Type I mAb neutralizes IL-6 activity by the blocking of IL-6 binding to its receptor directly. In contrast, Type II mAb neutralizes IL-6 activity not by direct blocking of IL-6 binding to its receptor, but by modulating the binding affinity of IL-6 to its receptor, that is, inhibiting the formation of high affinity binding in IL-6 receptor system. This also indicates that the formation of high affinity may be necessary to transduce the IL-6 signal.
Mol Immunol 1991 Nov
PMID:Analysis of interleukin 6 (IL-6)/IL-6 receptor system using monoclonal anti-IL-6 antibodies. 172 May


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>