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)

A mAb of the IgG1/kappa isotype was raised against human myelin basic protein (MBP) peptide acetyl 1-9. This mAb, termed F23, reacted with human MBP and human MBP peptides acetyl 1-9, 1-14, and 1-44, but not with MBP peptides 10-19, 80-89, or 45-89. According to the guidelines of the molecular recognition theory, a complementary peptide to human MBP peptide 1-9 was synthesized and used to raise murine mAb with anti-Id activity. Two mAb anti-Id, F25F7 and F25C8, both of the IgM/kappa isotype, were selected for further study. These anti-Id reacted with F23, the mAb for which they were selected, and also reacted with another mAb, which was of the IgG1/kappa isotype and was raised to human MBP peptide 80-89. There was no reaction with another control mAb of the IgG1/kappa isotype or murine myeloma IgG1. By immunoblotting techniques, it was demonstrated that the Id on each of the mAbs to MBP peptides was located on the kappa L chain but also could be recognized in nonreduced IgG. The cross-reactive anti-Id suppressed antibody secretion of Id-producing hybridoma cells in an Id-specific manner, and kinetic studies suggest an intracellular mechanism for the suppression. These cross-reactive Id among antibodies to different MBP peptides imply that the same V region genes of kappa L chains are involved in the selection of antibodies to an autoantigen, like MBP, and may play a role in the modulation of immune responses against MBP in certain inflammatory demyelinating diseases.
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PMID:An idiotype shared by monoclonal antibodies to different peptides of human myelin basic protein. 169 57

SJL/J and (SJL X PL) F1 hybrid mice were immunized with intact human myelin basic protein (MBP) or the three major peptic fragments of MBP, residues 1-38, 39-89, and 90-170. Immune spleen cells were fused with mouse myeloma P3 X 63Ag8 (NS1) cells in the presence of polyethylene glycol. Hybridoma supernatant culture fluids were screened for antibody to MBP by a solid-phase radioimmunoassay (RIA). The specificity of the monoclonal antibody (mAb) was characterized by RIA using the three major MBP peptic fragments and subfragments as well as MBP and MBP fragments of different species with known amino acid sequence differences. Six MBP mAbs were generated, one of them IgM isotype and the remainder IgG isotypes. One mAb each reacted against regions of residues 22-38, 39-69, 70-89, 90-116, and two reacted against residues 118-157. Immunoblots also showed that the five IgG mAbs were reactive against MBP and the peptic fragment of MBP containing the epitope. Immunohistochemical studies showed the IgG mAbs specifically stained myelinated fiber tracts in human brain tissue.
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PMID:Monoclonal antibodies to human myelin basic protein. 241 82

We have produced a monoclonal antibody against myelin basic protein that reacts with astrocytes, oligodendrocytes, and Schwann cells. This antibody was generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunized with delipidated white matter from adult rat corpus callosum. The antibody was characterized via solid-phase radioimmunoassay, immunoblot of SDS-PAGE, and by indirect immunofluorescence staining of monolayer cultures containing oligodendrocytes, astrocytes, and Schwann cells. Myelin basic protein (MBP) was shown previously to be present only in myelin producing cells in CNS and PNS (oligodendroglia and Schwann cells) and not in astrocytes. The binding of this monoclonal antibody to all 3 cell types suggests that these cells share a common epitope. This epitope may be related to a common progenitor cell.
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PMID:Astrocytes, oligodendrocytes, and Schwann cells share a common antigenic determinant that cross-reacts with myelin basic protein: identification with monoclonal antibody. 242 23

Increasingly it is being discovered that short segments of proteins can provoke an immune response. Sequential determinants are as important as conformational determinants. It is the thesis of this paper that a string of three amino acid residues (a tripeptide) is antigenic when it is located on a large carrier, that is, when it is part of a protein. Conceptually this has great explanatory power in understanding (a) autoimmune phenomena (b) the intriguing finding that monoclonal antibodies which are supposed to be exquisitely specific cross-react with disparate, non-homologous proteins. Clinical syndromes such as the neuropathies of myeloma, hepatitis and multiple sclerosis are discussed in the light of this concept by computer analysis of the putative antigenic sites of myelin basic protein, hepatitis B and A proteins and measles peptides.
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PMID:Autoimmune disease--pathogenesis through molecular mimicry at the tripeptide level. 243 63

Monoclonal antibodies against human and bovine 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.
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PMID:Monoclonal antibody production to human and bovine 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2. 244 13

Perturbation of myelinogenesis by monoclonal antibodies against galactolipids is being used to study the role of these lipids in oligodendrocyte differentiation. We report here a marked stimulatory effect on oligodendrocyte differentiation when mixed primary cultures initiated from 19-21 day fetal rat telencephala are grown in the presence of a monoclonal antibody against sulfogalactolipids. When such cultures were grown in the presence of the IgM antibody 04 [Sommer and Schachner, Dev Biol 83:311-327 1981], the oligodendrocytes formed aggregates connected by fasciculated processes. Immunofluorescence microscopy and biochemical analyses of treated cultures demonstrated 2-3 fold increases in the fraction of 04-positive cells expressing myelin basic protein, and in the levels of myelin basic protein RNA, myelin basic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase activity, and 35SO4 incorporation into sulfatide. Greater than 90% of the cells positive for myelin basic protein in treated cultures were in aggregates. The specific activities of oligodendrocyte markers were unaffected in control cultures grown with nonspecific myeloma IgM. Since there was no increase in the total number of 04-positive cells in treated cultures, the increases in the specific activities of the myelin protein markers appears to be due to an increase in the fraction of cells expressing these markers. Time course studies demonstrated that both the rate and extent of oligodendrocyte differentiation were enhanced in treated cultures. These data are discussed with regard to possible mechanisms of the stimulation, considering not only potential direct effects of the antibody on the cell physiology, but also possible indirect effects due to antibody-induced aggregation.
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PMID:Stimulation of oligodendrocyte differentiation in culture by growth in the presence of a monoclonal antibody to sulfated glycolipid. 246 78

Murine monoclonal antibodies (MAbs) selective for an idiotope on a monoclonal antibody (IgG1/kappa) to human myelin basic protein (MBP) peptide 80-89 were prepared by immunization with a synthetic decapeptide specified by RNA that is complementary to the mRNA for human MBP peptide 80-89. The monoclonal anti-idiotypic antibody (anti-ID) reacted with the MAb to human MBP peptide 80-89 but not with a MAb to bovine MBP peptide 79-88 or to murine myeloma IgG1. The reaction between the monoclonal anti-ID and the MAb to the human MBP peptide 80-89 could be inhibited by human MBP peptide 80-89 and to a more limited degree with human MBP peptide 76-85 and bovine MBP peptide 79-88, but not by human MBP peptides 69-81 and 85-96. Practically, the use of a complementary peptide for stimulating an anti-ID response permits a more selective and feasible method for preparing anti-ID reagents. Theoretically, these results provide further support for the molecular basis of the network hypothesis.
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PMID:Monoclonal idiotypic and anti-idiotypic antibodies produced by immunization with peptides specified by a region of human myelin basic protein mRNA and its complement. 246 71

Monoclonal antibodies against P0, myelin basic protein, or myelin-associated glycoprotein were generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with central and peripheral nervous system myelin proteins. The antibodies secreted were either IgG, IgM, or IgA. Clone C6B5 (iso-type IgM) secreted antibody(ies) that bound to both myelin basic protein and myelin-associated glycoprotein, although binding of antibody to myelin basic protein as detected by the immunoblot technique appeared to be much less than to the myelin-associated glycoprotein. Antibodies were characterized in solid-phase radioimmunoassay for their species cross-reaction, and histologically for the specificity of binding to myelin in central and peripheral nervous system tissues. These monoclonal reagents should prove valuable in studying CSF and myelin-producing cells, since in both cases the concentration of myelin proteins is low.
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PMID:Production and characterization of monoclonal antibodies to peripheral and central nervous system myelin. 620 14

We have previously demonstrated that retrovirus-mediated genes were transferred to mouse glioma cells in a meningeal gliomatosis model (Yamada et al.: Japanese Journal of Cancer Research 83:1244-1247, 1992). This retrovirus vector contains the Escherichia coli. beta-galactosidase (beta-gal) gene as a marker for integration of the lacZ gene, which is controlled by the SV40 early promoter. We investigated whether lacZ genes could be specifically controlled in mouse glioma cells by glial-specific promoters, including the 2.5 kb 5' flanking region of the mouse glial fibrillary acidic protein (GFAP) gene, the 1.3 kb 5' flanking region of the myelin basic protein (MBP) gene, and the 1.5 kb 5' flanking region of the myelin proteolipid protein (PLP) gene. Psi-2 packaging cells were transfected with each retrovirus vector (GFAP promoter-, MBP promoter-, and PLP promoter-lacZ) and the infectious virus particles were recovered from the supernatants. Blue staining for beta-gal was detected in various fibroblast, myeloma, and glioma cell lines transduced with the retrovirus BAG vector. On the other hand, blue staining was only detected in glioma cells after transduction with the lacZ gene-bearing retrovirus controlled by glial-specific promoters. The strongest promoter activity was detected after transduction with the retrovirus in which the MBP promoter controlled the lacZ gene. Mouse glioma cells transduced with retrovirus containing the MBP promoter directing the herpes simplex virus type 1 thymidine kinase (HTK) gene were extremely sensitive to ganciclovir, while the parental cells and cells transduced with retrovirus containing the lacZ gene were not sensitive to ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective expression of foreign genes in glioma cells: use of the mouse myelin basic protein gene promoter to direct toxic gene expression. 750 43

A recombinant soluble form of the catalytic domain of human ADAM-10 was expressed as an Fc fusion protein from myeloma cells. The ADAM-10 was catalytically active, cleaving myelin basic protein and peptides based on the previously described 'metallosheddase' cleavage sites of tumour necrosis factor alpha, CD40 ligand and amyloid precursor protein. The myelin basic protein degradation assay was used to demonstrate that hydroxamate inhibitors of matrix metalloproteinases (MMPs) were also inhibitors of ADAM-10. The natural MMP inhibitors, TIMP-2 and TIMP-4 were unable to inhibit ADAM-10, but TIMP-1 and TIMP-3 were inhibitory. Using a quenched fluorescent substrate assay and ADAM-10 we obtained approximate apparent inhibition constants of 0.1 nM (TIMP-1) and 0.9 nM (TIMP-3). The TIMP-1 inhibition of ADAM-10 could therefore prove useful in distinguishing its activity from that of TACE, which is only inhibited by TIMP-3, in cell based assays.
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PMID:The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. 1081 25


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