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)

A 78-year-old man was admitted because of lumbago and chest pain. A diagnosis of non-secretory primary plasma cell leukemia was made based on the laboratory findings and his history. However, the plaque-forming cells assay of bone marrow cells revealed secretion of monoclonal immunoglobulin from the myeloma cells. Hyperammonemia was detected in the serum. Although the patient was treated with 4 courses of combination chemotherapy (vincristine, adriamycin, cyclophosphamide, methylprednisolone), he died of respiratory failure five months after diagnosis. Autopsy showed widespread multiple myeloma and prominent infiltration of myeloma cell in the sinusoid of the liver. Recently, there have been a few reports which increased the plasma ammonia concentration with multiple myeloma. This report strongly suggested that liver infiltration of myeloma cell caused hyperammonemia.
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PMID:[Non-secretory primary plasma cell leukemia with hyperammonemia]. 206 85

The rate of gene conversions and double crossovers between transfected and integrated mu heavy chain immunoglobulin genes was measured in myeloma cells. The assay relies on correction of an integrated and defective mu heavy chain expression unit, present in a repeated head to tail array in the genome of the myeloma cell line J558L. Following electroporation of these cells with restriction fragments containing normal immunoglobulin sequences, targeted recombination events are identified by a complement-mediated haemolytic plaque assay measuring production of functional IgM. Recombination results in replacement of a segment of the target sequence with the exogenous sequence. Different crossover positions are possible, giving rise to alternative rearrangements of the target site. In the case of one of the recombinants we analysed, more than one of the repeated targets had undergone a conversion event. The efficiency of homologous recombination was shown to depend on the extent of homology between transfected and target DNA. A targeting efficiency of 1 x 10(-5) to 2 x 10(-5) was achieved when the exogenous DNA contained 10,000 bases of sequence homologous with the target.
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PMID:Replacement recombinant events targeted at immunoglobulin heavy chain DNA sequences in mouse myeloma cells. 211 9

A study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B-cell differentiation, namely, circulating surface Ig positive (SIg+) cells, Ig-secreting cells (plaque forming cells, PFC) and mitogen-induced PFC. By using kappa-lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B-cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen-induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B-cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P less than 0.02). ID and CE can therefore be considered as useful markers for discriminating between MGUS and myeloma, evaluating the clinical stability and predicting the clinical course.
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PMID:Aberrant expression of immunoglobulin light chain isotype in B lymphocytes from patients with monoclonal gammopathies: isotypic discordance and clonal B-cell excess. 211 8

We have estimated the frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting histoincompatible renal allografts. In a major plus minor antigen-incompatible DA-to-WF combination on day 4 post-transplantation, reverse protein A plaque assay demonstrated that in the graft the frequency of lymphoid cells secreting Ig was 1:850. A major locus-incompatible and minor locus-compatible, congeneic LBN-to-Lewis strain combination was then applied to estimate the specificity of the secreted antibody. The lymphoid inflammatory cells were fused with mouse myeloma cells, cultured under limiting dilution conditions, and assayed by ELISA to donor and irrelevant strain spleen cells. Among cells infiltrating the graft, the fusion frequency was 1:172 x 10(3) and the frequency of Ig-producing hybrids 1:400 x 10(3) (i.e., this assay was approximately three log orders less sensitive than the reverse pA assay). The frequency of hybridomas secreting specifics antibodies against donor MHC antigens was 1:720 x 10(3) (i.e., every second hybridoma deriving from inflammatory population produced specific Ig). In addition, there was at least one obviously polyspecific population of hybridomas, detectable only in the spleen and reactive with all rat strains tested with a frequency of 1:700 x 10(3). The inflammatory cells were also cultured directly under limiting dilution conditions, and the frequency of Ig-secreting cells was determined by ELISA. The frequency of inflammatory lymphocytes secreting detectable amounts of immunoglobulin in the supernatant was 1:14 x 10(3) in the graft (i.e., this assay was approximately one log order less sensitive than the reverse protein A plaque assay).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting renal allografts. 220 26

The effect of coculturing nonadherent and plastic adherent cells from the spleen with MOPC 104E KI81 for short (24 h) and long term (7 days) was investigated. In both culture systems, the effect of the spleen cells on the secretion of IgM by plaque-forming cells assay and growth of the plasmacytoma by cell counts and flow cytometry was measured. In these studies, a low effector:target (E:T) ratio which did not produce cytotoxicity to MOPC 104E cells was used. We observed that while nonadherent spleen cells from normal or MOPC 104E-primed mice inhibited secretion of IgM by the MOPC 104E cells, they stimulated the proliferation of MOPC 104E cells two times faster than MOPC 104E cells cultured alone. Plastic adherent cells from the spleens of normal mice or MOPC 104E-primed mice also inhibited secretion of IgM by the tumor cells as measured by plaque formation, and stimulated proliferation of MOPC 104E in 24 h coculture. Plastic adherent cells from normal nonprimed mice initially stimulated the myeloma to grow, but by 24 h, a large fraction of the population was in the G1 or possibly resting state. The effect of nonadherent and plastic adherent cells on the stem cell activity of MOPC 104E was also tested in 7-day colony-forming assays. Nonadherent cells had no effect on colony-forming units or plaque formation. Plastic adherent cells from normal spleen cells inhibited plaque formation by 68% but had no effect on colony formation. However, plastic adherent cells from spleens of mice primed in vivo with MOPC 104E tumor cells suppressed plaque formation by 98% and also reduced colony formation. The results showed that inhibition by macrophages of IgM production by MOPC 104E cells is independent of cell proliferation. The adherent macrophages from both normal and in vivo-primed spleen cells were Mac.1 positive after 7 days of coculture with MOPC 104E cells. However, the density of Mac.1 was greater on primed macrophages.
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PMID:Host response to myeloma: effect of syngeneic spleen cells on the growth and function of MOPC 104E myeloma in vitro. 235 Jul 18

Optimal activation of T15 idiotype-bearing B cells has been shown previously to be influenced by two subsets of Thy-1+, Ly-1+,2-sIg- helper T cells. One of the helper T cell sets appears to be T15 specific in that its presence results in a selective augmentation of T15-bearing anti-phosphorylcholine (PC) plaque-forming cell responses. To determine the precise specificity of the idiotype-specific helper T cell (ThId), Ly-1 T cells were tested in an in vitro anti-PC response for their ability to bind directly to T15 myeloma protein-coated plastic plates. Specificity of this binding was ascertained by competitive inhibition of plate binding using idiotypically related myeloma or hybridoma proteins. These data suggest that the Ly-1 T cells which augment T15-bearing plaque-forming cell responses can bind to T15-coated plates and are T15 idiotype specific. This approach is being used currently to attempt to clone ThId cells to further analyze their activation requirements and specificities.
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PMID:T15-specific helper T cells: analysis of idiotype specificity by competitive inhibition analysis. 240 4

Two different hemolytic plaque assay protocols that are commonly used to quantitate idiotype-positive antibody-secreting cells have been compared to a standard radioimmunoassay (RIA) to test for their ability to discriminate between related, but idiotypically distinct, clonotypes. The idiotype proband used in this analysis is the individual specific idiotype associated with the dextran-binding myeloma protein M104E (M104E IdI). Antibodies specific for this private idiotype (anti-M104E IdI) were purified by a combination of adsorption and affinity chromatography of the immunoglobulin fraction isolated from the sera of rabbits repeatedly immunized with M104E. The same affinity-purified anti-M104E IdI antibodies were used in the hemolytic plaque assays and in the RIA. In one of the plaque assays, the putative idiotype-positive antibody-forming cells were scored by lysis of target erythrocytes to which the anti-idiotype had been covalently coupled. In the other plaque assay, the idiotype-positive cells were determined indirectly by anti-idiotype inhibition of PFC produced on dextran-coupled target erythrocytes. The fidelity of these two assays to quantitate the M104E private idiotype expression in individual BALB/c mice after a single immunization with dextran B-1355S was determined by comparing the plaque assay data to the data generated by a double-antibody, post-precipitation RIA of either the antibodies in the serum or of monoclonal antibodies produced by hybridomas. Our data indicate that both plaque assay protocols reflect an overestimate of the actual expression of M104E private idiotype. By using a library of dextran-specific hybridomas (that have been characterized in an RIA with respect to their M104E IdI cross-reactivity), we have shown that the PFC overestimate of the M104E expression observed in dextran-immune mice is due to the inability of both plaque assay protocols to distinguish between dextran-specific clonotypes that express idiotypes cross-reactive with, but not identical to, the 104E IdI. We conclude that the plaque assay should be used only in conjunction with an RIA to estimate the idiotype expression. This is especially true in situations where closely related cross-reactive idiotype families exist.
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PMID:Failure of PFC inhibition assays to distinguish idiotypically between clonotypes that are readily distinguishable by RIA analysis. 241 May

Peripheral blood mononuclear cells (PBMC) from normal human donors were cultured in Marbrook flasks in the presence of purified IgG or IgA myeloma proteins. The culture supernatants were tested for their ability to suppress pokeweed mitogen (PWM)- or Epstein-Barr virus (EBV)-driven Ig synthesis by normal PBMC. Two supernatants from PBMC cultured with IgG and one from PBMC cultured with IgA were tested and suppressed PWM-driven Ig synthesis as measured by a reverse haemolytic plaque assay and by quantitation of the Ig secreted into the culture medium of the PWM-driven cells. This suppression was not restricted to the Ig isotype of the 'inducing' myeloma protein, but was extended to IgG, IgA, and IgM. The suppressive effect could be absorbed out with human IgG.
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PMID:Suppressor factors generated from human mononuclear cells by means of purified myeloma proteins. 241 68

Two stable lines of IgA lambda-producing plasma cells (KHM-1A and KHM-1B) that were free of the Epstein-Barr virus were established from a patient with multiple myeloma complicated by hyperamylasemia. Surface marker studies of the two cell lines showed that the cells had no surface immunoglobulins but were positive for cytoplasmic immunoglobulins (IgA lambda) and for HLA-DR and PCA-1. Secretion of IgA monoclonal immunoglobulin by the two lines was detected by a plaque-forming cell assay and by an enzyme-linked immunosorbent assay of culture media. KHM-1B cells also secreted alpha-amylase, but no such activity was detected in the culture-conditioned supernatant fluid of KHM-1A.
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PMID:Establishment and characterization of an amylase-producing human myeloma cell line. 245 53

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.
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PMID:[CALLA-positive leukemic multiple myeloma of IgA-kappa type]. 250 77


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