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)

Mouse and rat myeloma cell lines showed little or no rosette formation with sheep erythrocytes (SRBC) coated with rabbit IgG (rabbit EA) but showed marked rosette formation after treatment with trypsin, pronase or neuraminidase. These cell lines showed no rosette formation with SRBC coated with mouse IgG (mouse EA): treatment with trypsin enabled the detection of rosettes among the mouse myeloma cell lines but not by the rat myeloma cells. The F(ab')2 fragment of the anti-Fc receptor II antibody blocked the formation of rosettes with rabbit EA by mouse myeloma cell lines after treatment with trypsin. Aggregated mouse IgG1 and IgG2b subclasses strongly inhibited the formation of rosettes with rabbit EA, whereas aggregated mouse IgG2a showed a marginal inhibitory effect. A large amount of mouse IgG2a, however, caused significant inhibition. Our results also revealed that aggregated mouse IgG could bind to the rat myeloma cell line. The Fc rosette forming abilities of the enzyme-treated mouse and rat myeloma cells became reduced after cultivation both in the presence and absence of FCS but not after cultivation in the presence of cycloheximide, suggesting that cell surface substances, which may be glycoprotein that incompletely mask Fc receptors, are produced by myeloma cells.
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PMID:Studies on the Fc receptors and masking substances on mouse and rat myeloma cells. 297 95

The presence of Fc receptors for IgE on epidermal Langerhans cells (LC) from patients with atopic dermatitis (AD) was demonstrated by three different types of experiments. Firstly, cell-bound IgE on LC was removed by acid elution and restored by highly purified human myeloma IgE (IgE kappa). Secondly, after pepsin digestion of cell-bound IgE the number of LC staining with anti-human light chain (kappa, lambda) antibodies significantly decreased in contrast to the number of LC staining with anti-human epsilon heavy chain antibody. Thirdly, LC formed rosettes with sheep red blood cells (SRBC) coated with IgE kappa. Epidermal LC from normal non-atopic controls, did not form rosettes with SRBC-IgE. The SRBC-IgE rosette formation could be inhibited by preincubation with IgE kappa and BB10 (MoAb directed against the Fc receptor for IgE on human eosinophils, platelets and macrophages), but also with human IgG, whereas the SRBC-IgG rosette formation could be inhibited neither by IgE kappa nor by BB10. Both the SRBC-IgE and the SRBC-IgG rosette formation could be inhibited by OKT6 (anti-CD1) antibody. The results of inhibition studies with OKT6 antibody on the reconstitution of IgE on epidermal LC after acid elution suggest an associated expression of the CD1 antigen and the Fc receptor for IgE.
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PMID:Associated expression of CD1 antigen and Fc receptor for IgE on epidermal Langerhans cells from patients with atopic dermatitis. 297 37

Immunoglobulin Fc-binding activity was detected by indirect immunofluorescence employing fluorochrome conjugated F(ab')2 antibody fragments on acetone-fixed cell cultures infected with herpes simplex virus type 1 (HSV-1). Using this method the Fc receptor-like activity seemed to be restricted to the IgG class of human immunoglobulins. While IgG1, IgG2, and IgG4 myeloma proteins bind to this putative Fc gamma receptor at a concentration of 0.002 mg/ml, IgG3 myeloma proteins were without activity at 0.1 mg/ml. The binding activity was associated with the Fc fragments of IgG, while the pFc' fragments of IgG appeared to be unable to bind in this assay system. The reactivity and specificity of the HSV-1 Fc receptor was independent of both the type of tissue culture cells used and the strain of HSV-1 inducing the Fc receptor-like activity. The HSV-1-induced Fc receptor has a similar specificity for human immunoglobulin class and subclasses as staphylococcal Protein A. However, these two Fc receptors exhibit at least one striking difference. The IgG3 G3m(st) protein which binds to Protein A does not bind to HSV-1-induced Fc receptor. A possible reaction site for the HSV-1 Fc receptor on IgG could be at or near Asp 276.
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PMID:Binding site and subclass specificity of the herpes simplex virus type 1-induced Fc receptor. 298 35

Fc receptors for IgG1 and IgG3 on peripheral blood lymphocytes and monocytes were studied before and after temperature shift from 4-37 degrees C. The investigations were performed in the EA test using human erythrocytes sensitized with anti-Rh/D/antibodies of IgG1 (EA IgG1) and IgG3 (EA IgG3) subclasses. It occurred that lymphocytes and monocytes were able to bind IgG1 and IgG3 antibodies before and after shedding, however, lower percentage of rosette was observed after temperature shift. This decrease was similar in the EAIgG1 and EAIgG3 tests. The supernatants obtained during shedding occurred to contain active Fc receptors since the inhibition of rosette formation was obtained after the incubation of sensitized erythrocytes with these supernatants. IgG1 as well as IgG3 myeloma proteins inhibited rosette formation in both EAIgG1 and EAIgG3 tests. Our data might suggest that IgG1 and IgG3 anti-D antibodies are able to bind to the same Fc receptor on lymphocytes as well as on monocytes.
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PMID:Shedding of Fc receptor from mononuclear cells and their ability of binding IgG1 and IgG3 anti-Rh/D antibodies. 314 99

The specificity of the Fc gamma receptors on the X63.Ag8.653 nonproducing myeloma cell line has been examined for binding to IgG1-, IgG2a-, and IgG2b-containing antigen-antibody complexes. Complexes containing each of these subclasses bind, and the binding of each is inhibited by the others. Trypsin treatment did not inhibit the binding of any of these subclasses. Furthermore, the monoclonal anti-Fc receptor antibody 2.4G2 inhibits the binding of all three subclasses. These results, together with those of other investigators, suggest that there is a single FcR for IgG1, IgG2a, and IgG2b on mouse B cells which differs in its specificity from the macrophage Fc gamma R. This is confirmed by the fact that a mutant IgG2b myeloma protein which binds to the macrophage Fc gamma 1/gamma 2b receptor does not bind to the Fc gamma R on X63.Ag8.653.
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PMID:Fc receptors on cultured myeloma and hybridoma cells. 315 73

In order to develop a reagent capable of killing cells with high-affinity IgE Fc receptors, such as mast cells and basophils, ricin A-chain (the toxic portion of ricin) was conjugated to rat IgE myeloma protein, IR 162, via derivatization of the IgE by n-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) thus creating an IgE-immunotoxin. Monensin (10(-7)-10(-8)M), a carboxylic ionophore, facilitated IgE-ricin A-chain (3 X 10(-7)M) toxicity in a dose-related fashion ith significant reductions in [3H]leucine incorporation compared to cells exposed only to monensin. This enhanced toxicity could be inhibited by the addition of both anti-ricin A-chain or anti-IgE, suggesting that different routes of intracellular processing may play a role in determining the toxicity of the IgE-ricin A-chain conjugate. Ricin B-chain (5 X 10(-7) and 5 X 10(-8)M) added to free ricin A-chain (10(-6)-10(-8)M) reproducibly facilitated toxicity, and this toxicity could be inhibited (30-90%) by lactose (50 mM). Ricin B-chain also facilitated IgE-ricin A-chain (2.75 X 10(-8)M) toxicity; however, this toxicity was not affected by lactose. The data suggest that ricin B-chain potentiates the cytosolic access of internalized IgE-immunotoxin and that the binding and internalization of the toxin was mediated via the IgE Fc receptor. A second type of IgE-ricin A-chain conjugate was synthesized whereby both IgE and ricin A-chain were derivatized with SPDP. RBL cells were killed in a dose-dependent manner by this IgE-ricin A-chain conjugate (2.5 X 10(-6)-2.5 X 10(-9)M) without requiring the addition of monensin or ricin B-chain. These data indicate that the intracellular route and processing of internalized immunotoxin is critical to eliciting toxicity.
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PMID:IgE-immunotoxins. II. IgE-ricin A-chain. 350 Jan 50

A cDNA clone encoding human thymosin-beta 4 was isolated from a cDNA library prepared from peripheral blood leukocytes of a patient with acute lymphocytic leukemia. This clone contained the entire coding sequence of 43 amino acid residues of thymosin-beta 4 and had an initiation codon and two termination codons. The amino acid and nucleotide sequences in the coding region were well conserved between rat and human. Nine of 132 nucleotides were different in the coding sequences (93% homology), but the deduced amino acid sequences were identical. No signal peptide was found in the deduced protein sequence. Human thymosin-beta 4 mRNA, approximately 830 nucleotides in length, was about 30 nucleotides larger than rat thymosin-beta 4 mRNA. Expression of the human thymosin-beta 4 gene in various primary myeloid and lymphoid malignant cells and in a few human hemopoietic cell lines was studied. Northern blot analyses of different neoplastic B lymphocytes revealed that steady state levels of thymosin-beta 4 mRNA varied as a function of differentiation stage. Thymosin-beta 4 mRNA levels were decreased in myeloma cells as are class II human leukocyte antigen, Fc receptor, and complement receptor, suggesting a relationship between thymosin-beta 4 and the immune response. Thymosin-beta 4 mRNA was more highly expressed in mature granulocytes than in immature blastic cells. Treatment of THP-1 cells, a human monocytic cell line, with recombinant human interferon-lambda reduced the levels of thymosin-beta 4 mRNA. Its level decreased after differentiation of THP-1 cells into Ia+ macrophages, but increased after differentiation of HL-60 cells into Ia- macrophages. The pattern of thymosin-beta 4 gene expression suggests that it may play a fundamental role in the host defense mechanism.
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PMID:Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes. 350 Feb 30

Previous work has shown that IgG rheumatoid factors (RF) bind to the C gamma 2-C gamma 3 interface region of human IgG in the same area that binds staphylococcal protein A (SPA). Group A, C, and G strains of Streptococci possess Fc receptors that bind to IgG but not to fragments containing only the C gamma 2 or C gamma 3 domains. This work describes the binding site location on human IgG for the binding of the isolated Fc receptor from the T15 strain of a Group A streptococcus and its relationship to the site that binds SPA and the IgG RF. The isolated T15 Fc receptor (T15) with a molecular mass of 29.5 kD inhibited the binding of IgG RF to IgG. The binding of T15 itself to IgG was strongly inhibited by SPA (42.0 kD) and its monovalent fragment D (7 kD). Human IgG fragments consisting of the C gamma 3 domains did not inhibit the binding of T15 to IgG, whereas those with both domains were effective inhibitors. T15 did not bind to rabbit IgG fragments consisting of either the C gamma 2 or C gamma 3 domains, but did bind to those with both domains. An IgG3 myeloma protein was a poor inhibitor and has been shown to bind poorly to the IgG RF. Most IgG3 myeloma proteins did not bind to SPA. The substitution of Arg and Phe for His 435 and Tyr 436 is responsible for the poor binding of IgG3 to SPA and to the IgG RF. Chemical modification of His or Tyr on IgG reduced its ability to inhibit the binding of T15 to IgG. Reversal of the chemical modifications with hydroxylamine resulted in near complete restoration of inhibitory capacity. This information, collectively, coupled with the known positions in space of the His and Tyr residues in the C gamma 2-C gamma 3 interface region, verified that both His 435 and Tyr 436, and possibly His 310 and 433, are involved. These residues are also involved in binding SPA and the IgG RF. These data therefore indicate that the T15 Group A Streptococcal Fc receptor binds to the same location on the Fc of IgG as SPA and the IgG RF. The biologic relevance of these similarities between bacterial cell wall Fc receptors and IgG RF are not yet apparent, but suggest that RF could bear the internal image of these bacterial structures.
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PMID:T15 group A streptococcal Fc receptor binds to the same location on IgG as staphylococcal protein A and IgG rheumatoid factors. 354 19

The lectin-binding capacity of 96 normal human IgG, assessed by solid-phase radioimmunoassay, strikingly varied according to the lectin considered. Indeed, half of the IgG samples exhibited peanut agglutinin (PNA)- and pokeweed mitogen-specific binding capacities superior or equal to 4%, whereas less than 15% of IgG similarly bound to concanavalin A (Con A) and to phytohemagglutinin. The ability of those IgG to inhibit the Fc receptor (Fc-R) function of human monocytes, measured by a classical rosette assay, was inversely correlated to their binding ratios to PNA and Con A only. By affinity chromatography, three groups of IgG were separated: the IgG purified on agarose-PNA columns slightly reduced the Fc-R function (40-45% inhibition); the IgG purified on Sepharose-Con A columns exhibited the highest inhibitory properties (80-85% inhibition); the IgG that did not bind to PNA and Con A columns possessed intermediate inhibitory properties (65-70% inhibition). The different effect of IgG on Fc receptors was conserved when monocytes were first treated by trypsin and was unrelated to their specific binding to human monocytes, to their subclasses, and to their C1q- or protein A-binding capacities. Incubation of monocytes with D-galactose (10 mM) significantly improved their capacity to form IgG rosettes, whereas their incubation with D-mannose (10 mM) significantly reduced the Fc-R function. Scatchard plots of 125I-IgG1 myeloma protein binding to monocytes were linear under basal conditions, as well as after a prior incubation of the cells with D-galactose or D-mannose. Monocytes bound about 16,000 molecules of IgG1 per cell in each instance. In contrast, the mean association constant (Ka) for IgG1 binding was 2.59 +/- 0.50 X 10(8) M-1 under basal conditions, 4.4 +/- 0.75 X 10(8) M-1 after D-galactose incubation, and 1.35 +/- 0.50 X 10(8) M-1 after D-mannose incubation. These data suggest that the level of human monocyte Fc-R function blockade induced by human IgG depends mainly on the presence of "accessible" galactosyl or mannosyl residues in the Fc domain and that the modulation of the Fc-R function induced by these carbohydrates is due to a change in the affinity rather than in the number of single class of high-affinity binding sites.
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PMID:The spontaneous ability of normal human IgG to inhibit the Fc receptors of normal human monocytes is related to their binding capacity to lectins. 362 80

Three commercial preparations of immunoglobulin G prepared for administration by the i.v. route were tested for their physical integrity and in vitro biological activity. Size exclusion chromatography by HPLC in native and denaturing buffers together with SDS-PAGE analysis were used to determine whether covalent-bond cleavage had occurred as a result of procedures used in their preparation. C1 complement binding assays and measurements of competitive binding to an Fc receptor-bearing promonocyte cell line U937 were used to assess whether such changes had altered the capacity of these preparations to engage biological effector functions. A purified IgG1 myeloma protein was used as a reference standard. WinRho, an unmodified IgG, consisted almost wholly of monomeric IgG by HPLC size exclusion and showed no evidence of proteolytic fragments in denaturing buffers or on SDS-PAGE. Sandoglobulin, a product treated at pH 4 with pepsin, contained about 10% dimeric protein and, as revealed under denaturing conditions, about 2% fragments. Relative affinity of binding to U937 cells was similar to WinRho. C1 binding by Sandoglobulin showed normal activity with 50% inhibition at 2.8 nM. Gamimune, modified by partial reduction and alkylation, contained about 15% dimers. Between 20 and 30% of the preparation retained covalent interchain disulfides. Binding to U937 cells was two-fold weaker than the other preparations and binding to C1 was also diminished and modified. This accords well with previous reports of the deleterious effect of reduction and alkylation on Fc function.
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PMID:An examination of the structural and biological properties of three intravenous immunoglobulin preparations. 371 8


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