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)

We have shown that fluids collected from antigen-challenged skin blisters during the late phase reaction cause the release of substantial amounts of histamine (means = 42%, n = 14) from human basophils in vitro. Control fluids collected either during the immediate phase or from an unchallenged blister released less than or equal to 10% histamine from both basophils and lung mast cells. Late phase blister fluids induced low levels of histamine release from human lung cells (means = 11%, n = 4) that were slightly but not significantly greater than levels induced by control blister fluids. The characteristics of basophil release were similar to IgE-mediated stimuli in dose dependence, calcium and temperature requirements, and kinetics. The IgE dependence of the late phase blister fluid was demonstrated by desensitization of the basophils to anti-IgE, which obviated the response to anti-IgE and blister fluid but did not affect a non-IgE-mediated stimulus. Removal of the cell surface IgE with lactic acid also abolished the response to both anti-IgE and late phase blister fluid. Incubation of the "stripped" cells with serum containing IgE myeloma restored the response to anti-IgE but failed to affect response to late phase blister fluid. The characteristics of release obtained with this factor closely resemble those of an IgE-dependent histamine releasing factor from cultured macrophages previously described by our group.
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PMID:Identification of histamine releasing factor(s) in the late phase of cutaneous IgE-mediated reactions. 241 43

Human lung macrophages obtained from surgical specimens spontaneously secreted a factor(s) (which we term macrophage factor) during 24-hr culture that induced calcium-dependent histamine release from human basophils and lung mast cells. Macrophage factor induced noncytotoxic histamine release from purified (85%) basophils. The kinetics of release were relatively slow and similar to that of anti-IgE. We performed a series of experiments to test the IgE dependence of macrophage factor-induced release. Preincubation of basophils with anti-IgE in calcium-free medium resulted in complete desensitization to macrophage factor-induced histamine release (i.e., when calcium and macrophage factor were added to the basophils, no histamine release occurred), and preincubation with macrophage factor in calcium-free medium resulted in partial desensitization to anti-IgE-induced histamine release. Pretreatment of basophils with pH 3.9 lactic acid buffer, which dissociates basophil IgE from its receptors, markedly reduced the capacity of basophils to release histamine in response to macrophage factor. Basophils that were incubated with IgE myeloma (but not with IgG) after lactic acid treatment partially or completely regained their capacity to release histamine in response to macrophage factor. Fluid-phase IgE myeloma (15 micrograms/ml) (but not IgG) inhibited basophil histamine release induced by two macrophage-derived supernatants, whereas IgE myeloma (200 micrograms/ml) did not inhibit release due to other supernatants. IgE-affinity columns removed the histamine-releasing activity of five macrophage-derived supernatants, and IgG-affinity columns had similar effects. However, neither affinity column removed the histamine-releasing activity of three other macrophage-derived supernatants. On Sephadex G-75 chromatography, nearly all of the histamine-releasing activity migrated as single peak with an apparent m.w. of 18,000. These results suggest that, although macrophage factor are heterogeneous, they are related, as they are a IgE-dependent factors that induce histamine release by interacting with cell surface IgE. These macrophage factors may be responsible for stimulation of basophil/mast cell mediator release in chronic allergic reactions.
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PMID:Human lung macrophage-derived histamine-releasing activity is due to IgE-dependent factors. 241 44

A monoclonal antibody against rat neutrophils, RP-1, was produced by hybridizing a mouse myeloma (P3-X63-Ag8.653) with BALB/c mouse spleen cells sensitized with peritoneal neutrophils from Wistar-King-Aptakeman/Hok rats. RP-1 specifically reacted to neutrophils and bone marrow cells from rats of various strains. The expression of an antigen reactive to RP-1 on rat peritoneal neutrophils was enhanced by stimulation with phorbol myristate acetate and concanavalin A. The experimental result that the expression of an antigen reactive with another anti-neutrophil monoclonal antibody was not enhanced by stimulation with phorbol myristate acetate indicates that the antibody-binding capacity of stimulated neutrophils was not nonspecifically enhanced. The enhancement of antigen expression was temperature dependent. A glycolytic inhibitor, 2-deoxy-D-glucose, and an inhibitor of intracellular calcium mobilization, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester hydrochloride, which inhibited hydrogen peroxide release from stimulated neutrophils, did not inhibit enhancement of the expression of an antigen reactive with RP-1.
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PMID:Enhancement of the expression of a rat neutrophil-specific cell surface antigen by activation with phorbol myristate acetate and concanavalin A. 242 75

Nasal lavage fluids from unstimulated individuals contain a histamine-releasing factor (HRF) similar to those which we have previously described from macrophages, platelets, and from blister fluids obtained during the late cutaneous reaction. The nasal HRF was partially purified by ion-exchange chromatography and gel filtration. Although some m.w. heterogeneity was observed, the majority of the HRF eluted at an apparent m.w. range of 15,000 to 30,000. This partially purified HRF induced histamine release from basophils of certain individuals. Histamine release occurred via a mechanism which is IgE-dependent in that: basophils desensitized by exposure to anti-IgE in the absence of calcium no longer respond to HRF, and desensitization with HRF reduces responsiveness to anti-IgE; and removal of IgE from the basophil surface by using lactic acid renders cells unresponsive to HRF. We have further defined this IgE dependence and have shown that the reason that only selected basophil donors respond to HRF is due to a previously unrecognized, functional heterogeneity of IgE. Thus, passive sensitization using sera from responders restored the responsiveness of acid-stripped basophils and conferred responsiveness to basophils of a nonresponder with naturally unoccupied IgE receptors. Sera from nonresponders failed to do this even though similar numbers of IgE molecules were put onto the basophil surface in each case. This property of responder sera was due to IgE because both heating sera at 56 degrees C for 2 hr and passage of sera over anti-IgE-Sepharose (which removes greater than 90% of the IgE) markedly reduced the ability of sera to induce responsiveness, and because an excess of either purified IgE myeloma or purified penicillin-specific IgE antibody from a nonresponder competitively inhibited the ability of IgE from responder sera to induce responsiveness to HRF. We conclude that nasal lavage fluids contain an HRF which induces basophil histamine release in a specific, IgE-dependent fashion but only from individuals with the appropriate type of IgE. Because we have shown that basophils are recruited into the nose during the late-phase reaction, we suggest that nasal HRF may induce these cells to release histamine and other mediators which could contribute to the symptomatology of the late-phase reaction.
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PMID:Studies of IgE-dependent histamine releasing factors: heterogeneity of IgE. 243 89

In skeletal muscle, dihydropyridine receptors and dihydropyridine-sensitive Ca2+ channels are preferentially localized in the transverse tubular membranes. Starting with an antigenic membrane fraction enriched in rabbit muscle transverse tubules (T-tubules), several monoclonal antibodies were produced by a fusion of spleen cells from an immunized BALB/c mouse with P3 X 63Ag.8.6.5.3 mouse myeloma cells. Antibodies were screened according to a scheme designed to select IgG immunoglobins that recognized a determinant specifically associated with the T-tubule membrane. Antibodies that fulfilled the screening criteria were used in in vitro planar bilayer recording of the activity of the dihydropyridine-sensitive Ca2+ channel present in T-tubules. Cells producing one antibody (Ab 21) survived cloning dilution and stably produced a monoclonal antibody (mAb21-4) that increased the rate of single channel opening when interacting with the internal side of the channel protein. mAb21-4 immobilized by covalent crosslinking on beads (Affi-Gel 10) consistently immunoprecipitated polypeptide bands with the following electrophoretic mobility: Mr values of greater than or equal to 175,000; 90,000; 55,000; and 34,000.
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PMID:Monoclonal antibody specific for the transverse tubular membrane of skeletal muscle activates the dihydropyridine-sensitive Ca2+ channel. 244 40

The effects of oxatomide on the release of histamine and leukotriene C4 (LTC4) from human lung fragments and granulocytes were examined and the findings compared with the effects of the antiallergic drugs ketotifen, azelastine and tranilast. Oxatomide inhibited the release of both histamine and LTC4 from human lung fragments in cases of passive sensitization with human IgE myeloma serum upon anti-epsilon stimulation. IC50 values for the release of LTC4 from human lung fragments were as follows: oxatomide, 2.35 x 10(-5) M; azelastine, 27.2 x 10(-5) M; ketotifen, 52.1 x 10(-5) M; tranilast, 62.9 x 10(-5) M. Oxatomide also inhibited the release of both histamine and LTC4 from human mixed leukocytes stimulated by the calcium ionophore A23187. IC50 values for the release of LTC4 from human mixed leukocytes were as follows: oxatomide, 1.67 x 10(-5) M; azelastine, 3.65 x 10(-5) M; ketotifen, 12.2 x 10(-5) M; tranilast, 15.1 x 10(-5) M. The effects of oxatomide on the release of LTC4 from purified human neutrophils and eosinophils were also given attention. Oxatomide inhibited the release of LTC4 from eosinophils more effectively than from neutrophils and mixed leukocytes. As there is evidence that eosinophils play an important role in the development of late asthmatic responses and/or in the aggravation of asthma, oxatomide is expected to be an effective treatment for such conditions.
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PMID:Oxatomide inhibits the release of chemical mediators from human lung tissues and from granulocytes. 245 69

The peripheral blood and bone marrow mononuclear cell immunophenotype was investigated in series of 41 patients with plasma cell dyscrasias (29 with multiple myeloma and 12 with monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma). A statistically significant relationship between the presence of monotypic B-cells (MBC) in the peripheral blood and the paraprotein light chain isotype was found in the myeloma patients (P = 0.0025). MBCs were documented in 71% of patients with lambda paraproteins, compared with only 13% of patients with kappa paraproteins. The difference in MBC was independent of disease stage as well as of individual prognosticators such as haemoglobin, renal function, paraprotein size and beta-2-microglobulin, although lambda producers had significantly higher calcium levels than patients with kappa paraproteins (P = 0.03). A similar trend was also noted for MBC to be found more commonly in patients with lambda producing MGUS and solitary plasmacytoma. This phenomenon may account for the worse prognosis in patients with lambda paraproteins. In our hands, immunophenotypic detection of peripheral blood involvement in plasma cell dyscrasias is more sensitive than investigation of karyotype or immunoglobulin gene rearrangements.
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PMID:Circulating monotypic B-cells in multiple myeloma: association with lambda paraproteins. 250 24

A 48-year-old man developed a marked and persistent hypercalcemia 3 months after admission for paraplegia resulting from severe peripheral neuropathy most likely of alcoholic etiology. Serum ionized calcium was elevated, and parathyroid hormone levels were low normal by the two separate radioimmunoassays. Urinary calcium excretion was markedly elevated, and serum 1,25-dihydroxyvitamin D level was decreased. An extensive clinical evaluation for possible occult malignancy, myeloma, and sarcoidosis as a cause of hypercalcemia produced no positive findings. Treatment with calcitonin caused prompt normalization of serum calcium, and its discontinuation resulted in recurrence of hypercalcemia. With improvement of neuropathy, the patient started active physical therapy. We gradually discontinued calcitonin, and the patient's serum calcium remained normal during the following 11 months. We discuss difficulties in both clinical and laboratory diagnosis of hypercalcemia of immobilization in the adult patient because no specific laboratory test is available.
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PMID:Hypercalcemia of immobilization in an adult patient with peripheral neuropathy. 253 19

A Balb/c mouse was immunized with chick synaptic plasma membranes and monoclonal antibodies were produced by fusion of spleen cells with NS-1 mouse myeloma cells. One antibody, MAC-L1, immunoprecipitated more than 90% of the [3H]PN200-110-labeled calcium channels but only 20% of the omega -conotoxin receptor solubilized from the chick brain membranes. Thus possibly, a certain portion of the omega -conotoxin receptor in the chick brain is a dihydropyridine-sensitive calcium channel. By the specific immunoprecipitation of 125I-labeled proteins, two large polypeptides of 193kDa and 130kDa under reducing conditions were identified as the major components of the calcium channel.
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PMID:Identification of a dihydropyridine-sensitive calcium channel in chick brain by a monoclonal antibody. 255 Dec 70

Membrane currents through the Ca2+ channel were studied in a hybridoma cell line (MAb-7B) constructed by fusion of S194 myeloma cells and splenic B lymphocytes from the mouse. The whole-cell variation of the patch-electrode voltage-clamp technique was used. When [Ca2+]o = 2.5 mM, [Na+]o = 150 mM and [Na+]i = 155 mM, the current reversed from inward to outward at 20.9 +/- 2.4 mV (mean +/- S.D., n = 62). Both inward and outward currents showed voltage-dependent inactivation with the same membrane potential dependence of steady-state inactivation. The decay time constant of the current decreased from about 27 ms at -44 mV to a saturation value of 16 ms at about -20 mV, and remained at this value even when the current became outward. From the above results both the inward and outward currents were considered to flow through Ca2+ channels. The inward current showed no change when the external Na+ was replaced with Cs+ or tetraethylammonium and increased when [Ca2+]o was increased. Also, the reversal potential became more positive with increasing [Ca2+]o with a slope of 29 mV/decade change of [Ca2+]o. Effects of different divalent cations examined at 10 mM concentration showed the reversal potential to become more positive in the order of Mn2+, Sr2+ approximately equal to Ba2+ and Ca2+ whereas the relative maximum amplitudes of peak inward current were 1.0 for Ca2+, 1.24 for Sr2+, 0.99 for Ba2+ and 0.07 for Mn2+. When [Ca2+]o or [Mg2+]o was reduced by chelators, monovalent cations became capable of carrying inward current through the Ca2+ channel. These monovalent currents share common kinetic properties with the Ca2+ current, as judged from the steady-state inactivation and the decay time constant of the current. The monovalent cation current was blocked by divalent cations in a voltage-dependent manner. The half-blocking concentrations of Ca2+ and Mg2+ at -45 mV were 2.0 X 10(-6) M and 3.0 X 10(-5) M respectively. The same voltage-dependent binding mechanism can explain the outward current carried by monovalent cations at large positive potentials at normal Ca2+ concentrations. The suppression of the monovalent currents by Ca2+ and Mg2+ showed different voltage dependences. The suppression by Ca2+ increased and then decreased as the membrane potential was made negative, whereas the suppression by Mg2+ increased monotonically. This difference can be explained by considering the fact the Ca2+ is permeant and Mg2+ is impermeant through the Ca2+ channel.
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PMID:Currents carried by monovalent cations through calcium channels in mouse neoplastic B lymphocytes. 258 82


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