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)

To investigate individual components of the humoral immune response directed against the acetylcholine receptor in experimental myasthenia, we injected monoclonal antireceptor antibody into normal rats. These antibodies were produced by cloned hybridoma lines formed by fusion of immune spleen cells with the myeloma cell line P3-X63-Ag8. Antibodies from two of seven clones induced acute experimental myasthenia, manifested by clinical weakness, decremental electromyographic response to repetitive nerve stimulation, and diminished mean amplitudes of miniature end-plate potentials (mepps): 0.55 +/- 0.02 mv (SEM) versus 0.71 mv for controls (p less than 0.001). In clinically affected animals, mepp amplitudes from the diaphragm correlated with decremental responses in the gastronemius muscle (r = -0.91, p less than 0.01). The results suggest that binding of a single antibody species to a single determinant on the acetylcholine receptor molecule is sufficient to induce acute experimental myasthenia gravis.
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PMID:Myasthenia induced by monoclonal anti-acetylcholine receptor antibodies: clinical and electrophysiological aspects. 616 99

We investigated the ability of antigen-IgE interactions to stimulate histamine release from human infant cutaneous mast cells. Skin obtained at circumcision contained numerous perivascular mast cells, as assessed by light and electron microscopy. The histamine content of this tissue averaged 17.7 ng (+/- 1.5 SEM)/mg wet weight. Challenge of 200-microns thick sections of unsensitized skin with varying concentrations of monoclonal murine antibodies to human IgE caused no net release of histamine. After skin sections were incubated in the presence of 5 micrograms/ml of human myeloma IgE (S) for 120 min at 37 degrees C, monoclonal anti-IgE challenge resulted in 40.1% (+/- 6.0 SEM) histamine release. Similar passive sensitization with 1/20 dilutions of serum from humans expressing IgE to purified Juniperus sabinoides (JS) antigen rendered the tissue responsive to specific antigen challenge. Dose-related histamine release occurred over 30 min with optimal release of 12.6% (+/- 2.4 SEM) after stimulation with 100 ng/ml of JS antigen. This reaction required sensitization with serum containing IgE to JS and was antigen-specific. Optimal reactions to antigen occurred at 3 mM added Ca++, 34 degrees C to 37 degrees C, pH 7.2. Antigen-induced release was markedly influenced by the added Ca++ concentration; no release occurred in the absence of Ca++, 54% of the optimal response was observed at 2 mM Ca++, and 28% of the optimal response occurred at 4 mM Ca++. The addition of Mg++ did not influence antigen-induced release. The results of this study provide functional evidence that 1) human infant cutaneous mast cells express Fc-epsilon receptors; 2) these receptors are largely unoccupied in vivo; and 3) stimulation of passively sensitized infant mast cells with anti-IgE or specific antigen leads to immediate histamine release. This new system should permit detailed in vitro studies of immediate hypersensitivity reactions in human skin.
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PMID:IgE-mediated release of histamine from human cutaneous mast cells. 618 24

The mechanisms responsible for the unusual susceptibility of multiple myeloma (MM) patients to infections are incompletely defined. Since MM is associated with decreased production of normal serum proteins, we investigated the possibility that the production of opsonins might also be impaired. The neutrophil chemiluminescence assay of opsonization was used to evaluate the ability of serum from patients with MM to opsonize zymosan. It was found that sera from 18 MM patients exerted only 50% +/- 2.5% (mean +/- SEM) of the opsonic activity found in 18 control sera (p less than 0.001). In mixture experiments, untreated normal serum completely restored the opsonic activity of MM serum, suggesting a deficiency of opsonic factors rather than an inhibitor. In other mixture experiments, heat-inactivated normal serum only partially corrected the opsonic defect in MM serum. Serum from three patients had low C3 levels, and treatment of particles with these resulted in a greater opsonic defect than the patient population as a whole (p less than 0.02). No correlation between the opsonic defect and infections was established over an 18-mo period. These data suggest that MM serum lacks both heat-stable and heat-labile opsonic activity, the direct clinical significance of which remains to be clarified. However, these studies support the concept that defective host resistance in MM may be multifactoral, combining opsonic abnormalities with other defects previously described.
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PMID:Defective opsonization in multiple myeloma. 676 55

T-lymphocyte subpopulations bearing Fc receptors for IgM (T mu) or for IgG (T gamma) were studied in blood specimens obtained from 40 normal volunteers and from 16 patients with multiple myeloma. The myeloma patients showed a significant imbalance in T-cell subpopulations characterized by an increase in the percentages of T gamma cells to 30.0 +/- 3.9% (mean +/- SEM) compared with 12.0 +/- 3.0% for the controls (P less than 0.001). The patients exhibited a decreased proportion of T mu cells (13.4 +/- 4.1%) compared with the control value of 55 +/- 7% (P less than 0.001). When the results were analysed according to clinical status it was the patients with indolent or well-controlled disease and not those with progressive disease who exhibited an elevated proportion of T gamma cells. The elevation of T gamma cells or of a subpopulation of suppressor cells should be further studied as a possible mechanism of disease control in multiple myeloma.
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PMID:T-cell subpopulations in multiple myeloma: correlation with clinical disease status. 697 83

T lymphocytes express a unique I-A subregion-controlled surface molecule that is not expressed on B lymphocytes. We produced antisera and monoclonal antibodies recognizing this structure. Exhaustive B cell adsorption (A.TH X B10.HTT)F antiserum, produced against activated A.TL T cells, left antibodies that bind an I-Ak specificity on some B10.A(4R) T lymphocytes (11 +/- 2%, mean +/- SEM). Similarly, exhaustive B cell adsorption of (A/J X B10.MBR)F antiserum, produced against activated B10.A(5R) cells, left antibodies specific for an I-Ab determinant on B10.A(5R)T cells (17 +/- 2%). We fused A.TL-immune (A.TH X B10.HTT)F splenocytes with NS-1 myeloma cells and identified antibody-producing hybrid cells by a fluorescent enzyme-linked immunosorbent microassay described herein. Eight monoclonal antibodies were selected; these lyse 7--26% of peripheral T cells from I-Ak strains. Thymocytes and bone marrow cells do not express the I-Ak T cells determinant. Exhaustive B cell adsorption did not remove I-Ak T cell-specific monoclonal antibodies.
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PMID:Murine T cell-specific Ia antigens: monoclonal antibodies define an I-A-encoded T lymphocyte structure. 698 Apr 12

In order to evaluate the relationship of PGE2 to hypercalcemia in cancer patients, 101 patients were screened with a radioimmunoassay for plasma prostaglandin E2 (PGE2) (NL less than 100 pg/ml). Of the 101 patients, 31 were hypercalcemia. Mean PGE2 (+/- SEM) of the 31 patients was 199 +/- 36 pg/ml. Among the 70 normocalcemic patients, mean +/- SEM PGE2 was 85 +/- 12 pg/ml (range = less than 25--225 pg/ml) (P less than 0.001). Seventeen hypercalcemic patients were initially treated with saline and furosemide, then were prospectively screened for serum parathormone (iPTH) and PGE2. Fourteen of 17 patients were then treated empirically with indomethacin (25 mg b.i.d.) for 72 hours and the PGE2 assay was repeated. Prior to therapy with indomethacin (mean +/- SEM), Ca++ = 12.2 +/- 1.5 mg/dl (NL 8.4--10.6 mg/dl), PGE2 = 87.1 +/- 36.8 pg/ml, (range = less than 25--209 pg/ml), and iPTH = 406 +/- 266 pg/ml (NL less than 400 pg/ml) (range = less than 100--825 pg/ml). PGE2 was elevated before treatment in 6/14 patients (breast, colon, renal, lung, neck tumors, and myeloma). Following treatment with indomethacin, PGE2 and calcium fell to normal levels in three patients (breast, colon, renal carcinomas). These results suggest: (1) A bimodal distribution of PGEs exists in hypercalcemic cancer patients. (2). There was some evidence of lack of whole molecule iPTH suppression in these patients. (3) Multiple stimuli of calcium mobilization may play an important etiologic role in a few hyercalcemic cancer patients and may explain the failure of indomethacin to control serum Ca++ in some patients with elevated PGE2.
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PMID:A study of prostaglandin E2, parathormone, and response to indomethacin in patients with hypercalcemia of malignancy. 705 14

In this study we investigated the proliferation of three well-documented MM lines and 10 bone marrow samples from myeloma patients in response to rh-SCF alone and combined with Interleukin-6 (IL-6), IL-3 and IL-3/GM-CSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (> 90%) by immunomagnetic depletion of T, myeloid, monocytoid and NK cells. The number of S-phase cells was evaluated after 3 and 7 d of liquid culture by the bromodeoxyuridine (BRDU) incorporation assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a clonogenic assay. All the experiments were performed in serum-free conditions. RPMI 8226 cell line was not stimulated by SCF which also did not augment the proliferative activity of IL-6, IL-3 and PIXY-321. Conversely, SCF addition resulted in 2.4-fold increase of the number of U266 colonies and in a higher number of U266 and MT3 cells in S-phase (24.5 +/- 2% SEM v 14.5 +/- 1% SEM and 32 +/- 3% SEM v 21 +/- 4% SEM, respectively; P < 0.05). The c-kit ligand also enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines. Anti-SCF polyclonal antibodies completely abrogated the proliferative response of MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the same cell line. Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was found, in a biologically active form, in the supernatant of the two cell lines by the MO7e proliferation assay. When tested on fresh myeloma samples, SCF increased the number of S-phase plasma cells (4.7 +/- 1.6% v 3.4 +/- 1.3% in control cultures: P = 0.02). Significant proliferation was also induced by IL-6 (7 +/- 2.3% of BRDU+ cells; P = 0.006), IL-3 (5.3 +/- 1.3%; P = 0.01) and PIXY-321 (5.4 +/- 1.6%; P = 0.02). The addition of SCF significantly enhanced the proliferation of myeloma cells responsive to IL-6. In summary, our results indicate that SCF is expressed in MM cells and stimulates the proliferation of neoplastic plasma cells.
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PMID:Expression and functional role of c-kit ligand (SCF) in human multiple myeloma cells. 752 40

The purpose of this study was to evaluate the antigenic profile of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). The mobilization regimens consisted of high-dose cytarabine/mitoxantrone for patients with NHL, DexaBEAM for patients with HD, and high-dose cyclophosphamide (4 or 7 g per m2) for patients with MM. Cytotoxic therapy was supported by recombinant human G-CSF (Filgrastim, 300 micrograms/day sc) to shorten the period of neutropenia and to increase the number of circulating hematopoietic progenitor cells. The mean numbers of circulating CD34+ cells/microliters during leukocyte recovery were different between patient groups, 80.5 +/- 9.8 (mean +/- SEM) in low-grade NHL and 51.2 +/- 9.7 in high-grade NHL compared with 31.3 +/- 6.9 in HD and 24.4 +/- 4.1 in patients with MM. As a result, the greatest numbers of CD34+ cells/kg collected per leukapheresis were observed in patients with NHL, whereas the collection efficiency was substantially lower in patients with HD or MM. Patients with MM had also the smallest proportion of CD34+ cells in the mononuclear cell fraction (mean 0.79 +/- 0.10% versus 2.15 +/- 0.19% in low-grade NHL) but the greatest proportion of early CD34+ HLA-DR- progenitor cells (mean 2.38 +/- 0.51 versus 0.84 +/- 14% in low-grade NHL). Patients with MM had a mean proportion of CD34/c-kit+ cells that was twofold greater than that observed in patients with high- or low-grade NHL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of peripheral blood progenitor cells mobilized by cytotoxic chemotherapy and recombinant human granulocyte colony-stimulating factor. 753 8

Retinoic acid has been shown to induce growth inhibition in a variety of cell types including human myeloma cell lines. Bone marrow plasma cells from 31 multiple myeloma (MM) patients were cultured to investigate the activity of 13-cis-retinoic acid (cRA), all-trans-retinoic acid (tRA), interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and dexamethasone (DEX), alone or in combination, on in vitro proliferation and immunoglobulin (Ig) secretion. Both cRA and tRA inhibited proliferation: the labelling index (LI) of treated cultures/controls, was 0.47 +/- 0.05 (mean +/- standard error mean, M +/- SEM) P < 0.0001, and 0.67 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. The inhibitory effect of cRA was significantly superior to tRA (P = 0.0129) and IFN-alpha, similar to IFN-gamma and DEX. The combinations of cRA + IFN alpha, tRA + IFN-gamma, tRA + DEX did not show any synergistic effect on myeloma proliferation. In contrast, the combination cRA + DEX (0.29 +/- 0.04, M +/- SEM) markedly increased the effect of both cRA and DEX used as single agents. Ig synthesis was not significantly affected by CRA, tRA, IFN-gamma and the combination tRA + IFN-gamma. As expected, only IFN-alpha (P = 0.002) and DEX (P < 0.001) inhibited Ig production. The combinations cRA + IFN-alpha, cRA + DEX and tRA + DEX decreased Ig secretion to the same extent as IFN-alpha and DEX alone respectively. In conclusion, our data indicate that tRA and especially cRA strongly inhibited plasma cell proliferation but had no effect on Ig synthesis. The combination of cRA + DEX showed the highest degree of inhibitory activity of all cytokines, alone or in combination.
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PMID:Retinoic acid inhibits the growth of human myeloma cells in vitro. 773 54

Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.
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PMID:Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells. 791 64


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