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)

The present study investigates the fate of the cell-bound IgE by using a well-characterized rat basophilic leukemia cell line and a purifed IgE myeloma protein. Both histamine-releasing and nonreleasing cell lines were examined. In both cases, no evidence for cell-mediated IgE catabolism could be elicited. Both the dissociated IgE and the receptors remained intact for prolonged periods of time, as demonstrated by binding assays. Internalization and/or recycling of membrane-bound IgE could not be demonstrated by E. M. autoradiography. We found only limited time-dependent changes in accessibility to anti-IgE antibody, trypsin, or elution at low pH (2.9 to 3.1). A biphasic dissociation of cell-bound 125I-IgE during incubation in the presence of excess unlabeled IgE was reproducibly observed; the more slowly dissociated IgE was also less readily dissociated at pH 3.4. These studies lead us to conclude that, in vitro, IgE resides in a functional orientation on the surface of RBL-1 cells, for prolonged periods of time.
 ...
PMID:The fate of IgE bound to rat basophilic leukemia cells. 3 32

The half-lives of two classes of rat immunoglobulins with homocytotropic properties, i.e., IgE and IgG2a, in the circulating blood and in the skin were studied. The catabolism of both normal (reaginic) and pathological (myeloma) IgE proteins in circulation was found to be extremely rapid with a half-life of 12 h. In contrast, the half-life of IgE antibody in the homologous skin was calculated to be 7.4 days. On the other hand, the half-life of IgG2a in circulation was about 5 days regardless of normal or pathological origin. IgG2a protein was, however, rapidly cleared from the injected skin site with a half life of 2.4 days, a value not longer than that obtained with nonskin-sensitizing goat IgG. The results indicate that rat IgE has an extremely short half-life in circulation despite of its sensitization period in tissues, and that the affinity for the target cells, as well as the mode of sensitization, of the two classes of homocytotropic antibodies, IgE and IgG2a, is different.
 ...
PMID:Half-lives of two types of rat homocytotropic antibodies in circulation and in the skin. 4 47

A patient (E.M.) with marked eosinophilia and hyperimmunoglobulin E (IgE) has been followed for 4 years. Peripheral blood eosinophilia reached levels in excess of 18,000 cells/mm3 and serum IgE concentration increased to more than 210,000 units/ml (about 0.48 mg IgE/ml). The IgE has both lambda and kappa light chains and is therefore considered polyclonal. The patient has an increase in peripheral blood lymphocytes which stain for surface IgE. Transfer of the patient's plasma (plasmsEM) to a rhesus monkey did not induce peripheral boood eosinophilia. The half life of IgEEM in a rhesus monkey was 2.2 days, which is similar to the half life of myeloma IgE in human subjects. The condition was not associated with defined morbidity except for mild persistent pruritus. Various studies revealed no evidence for atopic parasitic, immune deficiency or neoplastic disease.
 ...
PMID:Massive polyclonal hyperimmunoglobulinemia E, eosinophilia and increased IgE-bearing lymphocytes. 4 11

E myeloma protein, PS, was reduced in different concentrations of dithiothreitol (DTT) for 1 hr followed by alkylation with 14C-iodoacetamide. The affinity of the reduced-alkylated molecules for target cells was evaluated by their ability 1) to sensitize primate skin in a reversed P-K reaction, 2) to sensitize human basophils in a reversed-type histamine release and 3) to block passive sensitization with reaginic antibody. Antibody-epsilon0 antibody was employed for reversed type reactions to avoid participation of cell-bound normal IgE in the reactions. The sensitizing activity of IgE did not change following reduction in 1 mM DTT, which split inter-heavy-light chain disulfide bond. The activity of IgE significantly diminished after reduction in 2 mM DTT followed by alkylation. This treatment resulted in the cleavage of two intra-epsilon-chain disulfide bonds, which are present between the hinge and the Fd portion of the molecules. The reduced-alkylated protein was capable of sensitizing primate skin and human basophils, however, a much higher concentration of the reduced-alkylated protein than the native protein was required for passive sensitization. The optimal sensitization period for the reversed P-K reaction was 3 hr with the reduced-alkylated protein. The protein had the ability to block passive sensitization with reaginic antibody. The reduced-alkylated protein and the native protein were labeled with 125I, and binding of these proteins with human basophils was examined by autoradiography. The results showed that affinity of the reduced-alkylated protein for basophils was less than that of native protein. Since the disulfide bonds split by 2 mM DTT were not included in the Fc portion of the molecules, the Fc fragment was obtained from the reduced-alkylated protein and was tested for affinity for basophils. It was found that the Fc fragment had higher affinity than the reduced-alkylated protein. Recovery of the affinity by papain digestion strongly suggested that cleavage of disulfide bonds in the Fab portion of the molecules induced conformational changes in the Fc portion which is involved in binding to the target cells. Reduction of IgE with 10 mM DTT followed by alkylation resulted in cleavage of 5 disulfide bonds, which is accompanied by a loss of both sensitizing and blocking activities. The fifth disulfide bond which was cleaved by 10 mM DTT, but not by 2 mM DTT, appears to be an inter-heavy chain disulfide bond in the Fc portion of the epsilon-chains. Neither epsilon1 nor epsilon2 determinants in the Fc portion of epsilon-chains were degraded by this treatment.
 ...
PMID:Biologic significance of disulfide bonds in human IgE molecules. 4 81

The binding of human myeloma IgE immunoglobulin on rat mast cells was studied by three independent techniques. A mixed agglutination reaction with anti-IgE-coated Sephadex granules demonstrated that only human IgE-coated rat mast cells were clearly agglutinated. This binding is strong (50% agglutination) in 3 min and progresses for 30 min (95% agglutination). Autoradiographic studies with 125I-labelled human serum proteins demonstrated the selective formation of grains on mast cells incubated with labelled IgE. Upon action of anti-IgE antiserum on IgE-coated rat mast cells, the mast cells released up to 47.5% of their total histamine content in a fluorometric histamine assay. A relationship was established between sensitizing doses of human IgE and histamine release. These results bring evidence for a binding of human IgE on rat mast cells and imply the existence of receptors for this immunoglobulin on mast cell membrane.
 ...
PMID:Binding of human IgE immunoglobulin to rat mast cells. A study by means of three independent techniques. 5 Oct 10

The concentration of IgE in the serum of Sprague-Dawley rats increased after infection with Nippostrongylus brasiliensis (NB). The IgE concentration in normal rats was less than 1 mug/ml. After re-infection with NB, the concentration increased in 100 to 300 mug/ml. Mast cells were purified from peritoneal cells of both normal and NB-infected animals. Purified mast cells from the infected animals released histamine upon exposure to NB antigen. The antibody specific for IgE released histamine from purified mast cells of both normal and infected animals. Dose-reponse curves of histamine release suggested that mast cells from NB-infected animals bear more IgE molecules than normal mast cells. Binding of 125I-labeled rat E myeloma protein with normal mast cells was demonstrated by autoradiography. Under the same experimental conditions, mast cells of infected animals were not labeled with 125I-IgE. Mast cells from both normal and infected animals failed to combine 125I-labeled IgG. The number of IgE molecules bound per mast cell was determined by incubating 125I-labeled IgE with purified mast cells. When mast cells were incubated incubated in 0.6 to 2 mug/ml of IgE, the number of IgE molecules combined with the mast cells from infected animals was about 10% of that bound with normal mast cells. The results indicated that a large proportion of IgE receptors on mast cells of infected animals was occupied by their own IgE. No significant difference was observed between normal mast cells and those of infected animals with respect to histamine content and intracellular levels of cyclic nucleotides.
 ...
PMID:Immunologic properties of mast cells from rats infected with Nippostrongylus brasiliensis. 5 73

A fragment of IgE with molecular weight of about 40,000 was identified by radioimmunoassay in human small intestinal fluid after fractionation by gel filtration chromatography. Digestion of E myeloma protein PS by pooled intestinal fluid, trypsin or chymotrypsin yielded a degradation product of similar molecular weight that probably consisted principally of epsilon 1 determinant-containing fragments. These findings suggest that IgE is secreted into the intestinal lumen and degraded there by pancreatic proteolytic enzymes, producing an enzyme-resistant portion of the amino-terminal part of the Fc region.
 ...
PMID:Studies on IgE in human intestinal fluids. 5 26

Changes in rat mast cell cyclic adenosine 3',5' monophosphate (cAMP) concentrations during stimulation of histamine release by concanavalin A (con A) and anti-IgE were studied. Con A caused an increase in cAMP with a mean peak level at 20 sec of 232% of control (range 164% to 365%). Con A-stimulated cells demonstrated falls toward control levels after 20 sec, but generally remained above control for at least 5 min. By 10 min cAMP had returned to control values. The con A effect on cAMP occurred in the absence of phosphatidyl serine but was markedly inhibited by 5 mM alpha-methyl-D-mannose. Anti-IgE induced a less marked increase in cAMP (157% of control, range 110% to 540% of control) which reached a peak at 20 sec. Two monospecific goat anti-rat myeloma IgE antisera induced similar changes in cAMP whereas normal goat IgG had no effect. These peak values were followed by a rapid decrease in cAMP. Within 2 min the cAMP content of anti-IgE stimulated cells had fallen to levels well below control and remained below control levels from 45 sec to over 15 min. Histamine release in both systems began after the peak cAMP levels, during the period of rapid destruction of cAMP.
 ...
PMID:Modulation of cyclic AMP in purified rat mast cells. III. Studies on the effects of concanavalin A and anti-IgE on cyclic AMP concentrations during histamine release. 6 Apr 47

Mast cells were obtained by long term culture of rat thymus cells on rat embryonic fibroblast monolayers. Pure mast cell preparations obtained culture were incubated with 125I-labeled rat E myeloma protein to study receptors for IgE on their surface. When the cells were obtained after 35 to 45 days culture, the average number of receptors per mast cell was 100,000 to 400,000. An equilibrium constant of the binding reaction between their receptor and rat IgE was in the order of 108 M-1. The histamine content of the cultured mast cells was 0.2 to 5 mug/106 cells. The measurement of histamine content in mast cells recovered after different periods of culture suggested that the histamine content increased with maturation. Even after 45 to 50 days culture, the histamine content of cultured mast cells was significantly lower than that in rat peritoneal mast cells. The cultured mast cells were passively sensitized in vitro with rat IgE antibody against Nippostrongylus brasiliensis. The sensitized cells released histamine upon incubation with the antigen. It was also found that cultured mast cells released histamine upon exposure to compound 48/80. These results indicated that cultured mast cells have physiologic functions similar to those of normal rat mast cells, but they have not reached full maturation.
 ...
PMID:Development of mast cells in vitro. II. Biologic function of cultured mast cells. 6 15

Human myeloma proteins of IgG4 subclass in contrast to myeloma proteins IgG1, IgG2 and IgG3, were capable of blocking PCA reactions in monkeys mediated by human reaginic antibodies of IgE class. In addition to IgE, IgG4 myeloma protein was also capable of sensitizing leukocytes from normal individuals and gave histamine release (HR) upon challenge with anti-human IgG4. Leukocytes from 11 allergic individuals and from 9 normal subjects sensitized with the serum of allergic patients, were capable of releasing histamine with anti-human IgG4, anti-human IgE, and the specific allergen. No response was obtained with anti-human IgG1 and IgG3 sera. Leukocytes from the normal individuals released histamine from 3 to 20% with anti-human IgG4 and from 6 to 30% with anti-human IgE. Moreover, normal leukocytes sensitized with IgG4 myeloma protein or a serum of an allergic patient heated at 56 degrees C for 2 h, released a significant amount of histamine on challenge with anti-human IgG4 whereas no response was obtained with anti-human IgE. The biological role of human IgG4 in immediate hypersensitivity reactions is discussed in relation to human IgE.
 ...
PMID:Inhibition of reagin-mediated PCA reactions in monkeys and histamine release from human leukocytes by human IgG4 subclass. 6 38


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