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)

The noncovalent interaction of light (L) chain with heavy (H) chain or Fd isolated from a human myeloma protein Jo (IgG1, kappa) was studied by following circular dichroic (CD) change at 235 nm. The dimerization constants of Jo-L chain determined by measuring the CD change at 293 nm with protein concentration showed that the Jo-L chain exists as the monomeric form under the experimental conditions used for recombination with H chain. The second-order rate constants for the interaction between H and L chains were in good agreement with those for the interaction between Fd and L chain at various pH values. The binding behavior of L chain to Fd could be described by a single association constant. In the interpretation of the binding of L chain to H chain, however, it was necessary to assume that the binding of L chain to one of the two sites on H chain dimer (H2) decreases the affinity of the other site for L chain. The binding constant of the first L chain to H2 was the same as that of L chain to Fd. Renaturation processes of L chain, Fd, Fab(SS) fragment (with intact interchain disulfide bond), and Fab(RA) fragment (in which the interchain disulfide bond had been reduced and alkylated) from the denatured states in 0.5 or 1 M acetic acid on neutralization were studied. The renaturation of Fd occurred very rapidly, while that of L chain consisted of a very rapid process and a slow process which followed first-order kinetics. The renaturation process of Fab(SS) consisted of rapid and slow phases, of which the latter followed first-order kinetics. The renaturation process of Fab(RA) also consisted of rapid and slow phases, but the latter process followed second-order kinetics. The overall rate constant of renaturation of Fab(RA) was the same as that of the reformation of Fab(RA) from isolated Fd and L chain. On the basis of these facts, the kinetic mechanism by which Fd and L chain recombine to yield Fab(RA) can be described in terms of the scheme Fd + L in equilibrium Fd ... L leads to Fab(RA), where Fd ... L is an intermediate, and CD change is only observed in the second unimolecular process and not in the first bimolecular process.
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PMID:The mechanism of reassembly of immunoglobulin G. 1 49

Paraffin-embedded tissues of 47 cases of multiple myeloma and 4 cases of macroglobulinemia were studied by the immunoperoxidase indirect sandwich technique for identification of intracytoplasmic immunoglobulin. Specific immunoglobulin with a single heavy and/or light chain was readily detected in the neoplastic cells. Studies were performed on iliac crest bone marrow biopsies which had been fixed and decalcified using Zenker's-acetic acid solution and on tissues from various sites which had been fixed in formalin. An excellent correlation was obtained between the specific immunoglobulin detected intracellularly in the plasma cells or lymphoplasmacytic cells and the monoclonal immunoglobulin found in serum or urine of these cases. The immunoperoxidase technique represents a sensitive and specific method for identifying intracellular immunoglobulin in paraffin-embedded tissues.
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PMID:Specific identification of intracellular immunoglobulin in paraffin sections of multiple myeloma and macroglobulinemia using an immunoperoxidase technique. 40 69

The interactions among the subunits of a unique set of mouse myeloma proteins having specificity for beta-D-(1,6) galactans has been studied by making homologous and heterologous recombinants of heavy and light chains. The recombinations were carried out by mixing together the desired heavy and light chains that had been separated on a Sephadex G-100 column in urea-acetic acid and renaturing the chains at near neutral pH. One homologous and six heterologous recombinants have been prepared. All the recombinants prepared possessed a four-chain native-like structure. The ligand binding activity and idiotypic specificity of the homologous recombinant were essentially indistinguishable from those of the original native protein. All the heterologous heavy-light chain combinations also led to the regeneration of functional binding sites. The affinity of the heterologous recombinants towards various galactose ligands was comparable to those of the native molecules. Furthermore, the ligand binding affinity of the recombinants was almost invariably closer to the Ka of the original protein that had a higher affinity. Idiotypic specificity of the heterologous recombinants paralleled that of the original protein that had contributed the heavy chain.
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PMID:Subunit interactions in mouse myeloma proteins with anti-galactan activity. 81 9

Fv fragments prepared from the BALB/c anti-dinitrophenyl (DNP) myeloma proteins, produced by plasmacytoma MOPC 315 and XRPC 25, were used to raise anti-idiotypic antibodies in rabbits. Anti-idiotypes to these proteins were also prepared in the syngeneic BALB/c mice by injecting the intact proteins, whereas Fv fragment failed to induce antibodies in these mice. Rabbit anti-Fv of late bleedings did not show the presence of antibodies to "framework determinants" (determinants common to all V regions of mouse immunoglobulins), and they contained precipitating anti-idiotypes whereas mouse antisera contained non-precipitating anti-idiotypes. No cross-reaction was observed between anti-idiotypes to these myeloma proteins and induced anti-DNP antibodies from BALB/c mice, when either rabbit or mouse antisera were analyzed. The anti-sera were fractionated into anti-binding site and anti-non-binding site by adsorption onto the immunogen-Sepharose column and elution by DNP lysine, followed by elution with acetic acid. Only the anti-binding sites were inhibited by hapten in their interaction with the homologous myeloma protein. The rabbit anti-Fv antibodies were predominantly (over 90%) anti-non-binding site whereas the mouse anti-idiotypes were predominantly (60 to 70%) anti-binding site.
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PMID:Preparation and subfractionation of isologous and heterologous anti-idiotypes, using FV fragments. 99 90

Calf thymus histones (individually isolated or mixtures) and high mobility group proteins were ADP-ribosylated in vitro using [32P]NAD+ and immobilized purified poly(ADP-ribose) polymerase. The modified histones were then subjected to V8 protease or alpha-chymotrypsin digestion and the resulting peptides were separated by electrophoresis on acetic acid-urea-Triton gels. It was found that in vitro ADP-ribosylated histones were much more resistant to proteases than unmodified histones. A similar approach was applied to histones modified by the endogenous poly(ADP-ribose) polymerase in permeabilized NS-1 mouse myeloma cells in culture. In this case, the proteases could not discriminate between modified and unmodified histones and putative mono(ADP-ribosyl)ated peptides appeared in a digestion frame corresponding to that of bulk peptides. These differences are most probably due to the specificity or number of ADP-ribose groups added to the histones by the endogenous or exogenous poly(ADP-ribose) polymerase. Thus, depending on the size of poly(ADP-ribose) attached to nuclear proteins, these modified proteins might display different degrees of resistance to proteolysis.
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PMID:Resistance of ADP-ribosylated histones and HMG proteins to proteases. 129 46

One hundred and ten bone marrow trephine biopsies were studied from January 1987 to July 1989, using Zenker's acetic acid as fixative and routine paraffin embedding. Trephine biopsies were useful in differential diagnosis of cytopenias, especially when bone marrow aspiration was hypocellular or a dry tap, and in staging of lymphomas and multiple myeloma.
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PMID:Experience with bone marrow trephine biopsy. 145 33

Optic neuropathy induced by radiation is an infrequent cause of delayed visual loss that may at times be difficult to differentiate from compression of the visual pathways by recurrent neoplasm. The authors describe six patients with this disorder who experienced loss of vision 6 to 36 months after neurological surgery and radiation therapy. Of the six patients in the series, two had a pituitary adenoma and one each had a metastatic melanoma, multiple myeloma, craniopharyngioma, and lymphoepithelioma. Visual acuity in the affected eyes ranged from 20/25 to no light perception. Magnetic resonance (MR) imaging showed sellar and parasellar recurrence of both pituitary adenomas, but the intrinsic lesions of the optic nerves and optic chiasm induced by radiation were enhanced after gadolinium-diethylenetriaminepenta-acetic acid (DTPA) administration and were clearly distinguishable from the suprasellar compression of tumor. Repeated MR imaging showed spontaneous resolution of gadolinium-DTPA enhancement of the optic nerve in a patient who was initially suspected of harboring recurrence of a metastatic malignant melanoma as the cause of visual loss. The authors found the presumptive diagnosis of radiation-induced optic neuropathy facilitated by MR imaging with gadolinium-DTPA. This neuro-imaging procedure may help avert exploratory surgery in some patients with recurrent neoplasm in whom the etiology of visual loss is uncertain.
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PMID:Radiation-induced optic neuropathy: a magnetic resonance imaging study. 174 42

A monoclonal antibody (Jel 318) was produced by immunizing mice with poly[d(TmC)].poly[d(GA)].poly[d(mCT) which forms a stable triplex at neutral pH. Jel 318 did not bind to calf thymus DNA or other non pyrimidine.purine DNAs such as poly[d(TG)].poly[d(CA)]. In addition the antibody did not recognize pyrimidine.purine DNAs containing mA (e.g. poly[d(TC)].poly[d(GmA)]) which cannot form a triplex since the methyl group blocks Hoogsteen base-pairing. The binding of Jel 318 to chromosomes was assessed by immunofluorescent microscopy of mouse myeloma cells which had been fixed in methanol/acetic acid. An antibody specific for duplex DNA (Jel 239) served as a control. The fluorescence due to Jel 318 was much weaker than that of Jel 239 but binding to metaphase chromosomes and interphase nuclei was observed. The staining by Jel 318 was unaffected by addition of E. coli DNA but it was obliterated in the presence of triplex. Since an acid pH favours triplex formation, nuclei were also prepared from mouse melanoma cells by fixation in cold acetone. Again Jel 318 showed weak but consistent staining of the nuclei. Therefore it seems likely that triplexes are an inherent feature of the structure of eucaryotic DNA.
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PMID:A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes. 243 28

The generation of anti-IgE monoclonal antibodies has permitted the identification of various serological epitopes on the IgE molecule. The relationship of the sites on IgE recognized by such antibodies to the Fc epsilon receptor (Fc epsilon R) interaction site has been determined using cross-inhibition studies. However, interpretation of this type of experiment is limited by problems of steric hindrance. Thus, to accomplish precise mapping on the IgE molecule of the Fc epsilon R interaction site and the binding sites of various anti-IgE mAb, we employed site-directed mutagenesis of the IgE heavy chain gene. To this end we have constructed and expressed a recombinant murine constant epsilon heavy chain (C epsilon) gene bearing a (4-hydroxy-3-nitrophenyl)acetic acid (NP)-binding VH region. Several site-specific mutants in the C epsilon 3 and C epsilon 4 domains of this recombinant C epsilon gene were prepared and expressed by transfection into the light chain-producing J558L myeloma cell line. The resulting IgE antibodies were tested for binding to mast cells and to various anti-IgE mAb. The mutants produced include a proline to histidine point mutant at amino acid residue 404 in the C epsilon 3 domain, a mutant with a truncated C epsilon 4 domain, a mutant with a 45 amino acid deletion in the carboxy end of C epsilon 3, and a chimeric human C epsilon in which the human C epsilon 3 was replaced by the homologous mouse C epsilon 3 domain. These mutants have permitted the localization, to the C epsilon 3 domain, of the epitopes recognized by the 84.1C and 95.3 anti-IgE mAb. The 84.1C mAb recognizes a site on IgE which is identical or very close to the Fc epsilon R binding site, and 95.3 recognizes a site on IgE which is related, but not identical to the Fc epsilon R binding site. The antigenic determinant recognized by the 51.3 mAb, which is inefficient at blocking the IgE-Fc epsilon R interaction, has been mapped to the C epsilon 4 domain. When tested for binding to the Fc epsilon R on RBL-2H3 cells, the point mutant bound to the Fc epsilon R with twofold reduced affinity, while the C epsilon 3 deletion mutant and the mutant truncated in C epsilon 4 lost all receptor binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mapping of murine IgE epitopes involved in IgE-Fc epsilon receptor interactions. 247 7

The secretion of immunoglobulin (Ig) from cultured mononuclear cells by lipopolysaccharide (LPS) stimulation is inhibited by monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma. In an attempt to develop a murine monoclonal antibody (MAb) with specific reactivity against MNSF, a cell fusion technique that incorporated immune murine splenocytes and HAT-sensitive murine myeloma cells was used. Cross-reactivity experiments confirmed that the MAb (MO6) does not bind to unrelated proteins such as bovine serum albumin, mouse IgG, and murine interferon-gamma (IFN-gamma). There are no effects when anti-IFN-gamma antibodies are used with MNSF. As far as biological activity is concerned, MO6 inhibits in vitro the activity of MNSF in terms of the Ig secretion from cultured lymphocytes. By using MO6, affinity chromatography and immunoblotting were performed. The MNSF on the SDS-PAGE showed a band with m.w. of approximately 70,000, indicating the formation of an aggregate in saline; but after treatment with 0.4 M pyridine-acetic acid buffer, separate bands of 24,000 and 16,000 daltons were evident. Therefore MO6 recognizes 70,000 and both 24,000 and 16,000 daltons. Thus we confirmed by using this MAb and affinity chromatography, the existence of human counterpart, human nonspecific suppressor factor (hNSF), in supernatant from concanavalin A-stimulated T cells. When hNSF was fractionated by high pressure liquid chromatography (HPLC), the activity was found in a region corresponding to 70,000 daltons. However, when fractionated in pyridine-acetic acid buffer, hNSF activity was distributed in a slightly wider range of 15,000 to 30,000 daltons. Physicochemical analysis showed that the purified hNSF is resistant to either heating at 56 degrees C or to 2-mercaptoethanol treatment; however, it is labile to acidification at pH 2.0 and is also sensitive to protease treatment, the characteristics of which were similar to those of murine MNSF. Thus MO6 was confirmed to be a pertinent tool for isolation of hNSF, as well as for murine MNSF.
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PMID:Characterization of monoclonal nonspecific suppressor factor (MNSF) with the use of a monoclonal antibody. 310


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