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 thymuses with more than 99% T cells have been reported to contain immunoglobulin kappa mRNA-like molecules (kappa RNA) in relatively large quantities. The present study was undertaken to rule out the possibility that the kappa RNA was mainly a product of a few contaminating B cells of the thymus and to determine whether all T-cell subpopulations contained kappa RNA. By in situ hybridization with DNA complementary to kappa mRNA (kappa cDNA) the following observations were made: 98.5% of thymus cell preparations hybridized with kappa cDNA; the 1.5% unlabeled cells were generally larger and paler staining than the majority of thymus cells. Only 0.015% of thymus cells were intensely labeled and appeared to be plasma cells. Also, 87% of spleen cells hybridized with kappa cDNA; most of these showed similar labeling intensity to the majority of thymus cells. The number of unlabeled cells corresponded to the percentage of hemopoietic cells and macrophages in the spleen. Spleen cells in the range of 0.37-0.85% were intensely labeled and appeared to be plasma cells. The following controls supported the conclusion that the results with thymus and spleen were due to specific hybridization: most of the kappa mRNA-deficient tissue culture cells of the plasmocytoid tumor ABPL-4 did not hybridize with kappa cDNA. The kappa mRNA-producing cells from myeloma PC 3741 hybridized in situ with kappa cDNA. Furthermore, all cells from this tumor and all spleen cells hybridized uniformly with a cDNA probe complementary to most of the total cellular poly(A)-containing RNA species of these cells. These results indicate that T cells of all types in the thymus as well as in the periphery contain substantial quantities of kappa RNA.
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PMID:Direct demonstration of immunoglobulin kappa chain RNA in thymus T cells by in situ hybridization. 9 43

In this analysis, I have concentrated on advances in immunology, kinetics, and clinical oncology which have provided a substantial basis for identifying major common features in the natural history and pathophysiology of B-cell neoplasia as diverse as MM, MG, BMG, and NL. Observations on the natural history of both experimental and clinical myeloma as well as studies of kinetics of proliferation of MM and BMG in man provide the basis for reasonable hypotheses. Firstly, malignant variants of B-cell neoplasms may result from a two-hit evolution. In this scheme, the first hit is a triggering by specific antigen which leads to a required monoclonal expansion, while the second hit is the oncogenic event. Some cases of BMG seem to be examples of an unusually prolific response to the first hit, while others appear to be minimal deviation malignancies after the second hit. In this latter circumstance, the neoplastic clone in BMG usually retains a significant degree of sensitivity to tumor mass-related feedback inhibition. This may occasionally be lost during subsequent subcloning. Significant future testing of these hypotheses may prove feasible through the application of the in vitro tumor colony-forming assay system as it lends itself to study of a number of the salient features of these disorders.
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PMID:Neoplastic proliferation and natural history of B-cell neoplasia. 10 71

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.
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PMID:Interferon therapy in multiple myeloma. 10 25

An unusual case of a light chain plasma cell myeloma is described. The disease was initially characterized by a diffuse lymphoplasmacytic bone marrow involvement, but subsequently developed widespread extramedullary metastases with anaplastic tumors in the skin which histologically resembled a "histiocytic lymphoma." Electron microscopic examination, in vitro protein synthesis of bone marrow lymphoidal cells, chemical and immunochemical studies of serum and urine proteins, and intracellular immunoglobulin study by the immunoperoxidase technique on the skin biopsy and postmortem tumor tissue demonstrated evidence for lambda light chain synthesis and secretion. These findings provide further support to the notion that the wide spectrum of diverse morphologic patterns seen in lymphoplasmacytic disorders originates from the same progenitor B-lymphoid cell. Distinguishing anaplastic variant of plasma cell myeloma from other undifferentiated neoplasms offers a challenge.
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PMID:Lymphoplasmacytic myeloma: an immunological, immunohistochemical and electron microscopic study. 11 Apr 36

The complete amino acid sequence of the mouse mu chain from the BALB/c myeloma tumor MOPC 104E is reported. The C mu region contains four consecutive homology regions of approximately 110 residues and a COOH-terminal region of 19 residues. A comparison of this mu chain from mouse with a complete mu sequence from human (Ou) and a partial mu chain sequence from dog (Moo) reveals a striking gradient of increasing homology from the NH2-terminal to the COOH-terminal portion of these mu chains, with the former being the least and the latter the most highly conserved. Four of the five sites of carbohydrate attachment appear to be at identical residue positions when the constant regions of the mouse and human mu chains are compared. The mu chain of MOPC 104E has a carbohydrate moiety attached in the second hypervariable region. This is particularly interesting in view of the fact that MOPC 104E binds alpha-(1 leads to 3)-dextran, a simple carbohydrate. The structural and functional constraints imposed by these comparative sequence analyses are discussed.
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PMID:Amino acid sequence of a mouse immunoglobulin mu chain. 11 Dec 47

The BALB/c myeloma tumor, Y5781, has a high level of mu heavy chain mRNA and kappa light chain mRNA, as suggested by denaturing gel analyses of poly(A)-rich, total polysomal mRNA, and confirmed for the mu heavy chain mRNA by kinetic complexity analyses. Both the mRNA coding for the heavy and light chains appear as very prominent and discrete peaks above the generally polydisperse background of the total polysomal mRNA. This mRNA level appears to be stable through a limited number of subcutaneous passages of this myeloma, providing a potentially useful system for mu heavy chain mRNA synthesis and processing. The mu heavy chain mRNA of this myeloma has been enriched to about 60% homogeneity by physicochemical means. In agreement with a previous report (Faust, C.H., Jr., Heim, I., and Moore, J. (1979) Biochemistry 18, 1106-1119), the following physical and biological properties were observed. The mature cytoplasmic mu heavy chain mRNA is 950,000 daltons, i.e. about 2800 nucleotides, and contains approximately 800 undefined, nontranslated bases. In an mRNA-dependent cell-free system, this mRNA stimulates the synthesis of a single, serologically reactive mu heavy chain-like protein, confirmed by tryptic peptide maps.
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PMID:Mouse immunoglobulin mu heavy chain mRNA of Y5781, a high yield myeloma. 11 61

Lymphoid cells from normal and immunized BALB/c mice could be stimulated in vitro by syngeneic PCT contrasted with an absence of response to a number of other tumors. Maximal responses of normal cells to PCT were found to occur 5 days after the initiation of the cultures at an optimal responding:stimulation cell ratio of 1:2. MLTI activity of normal cells could not be blocked or enhanced by PCT myeloma protein products indicating that MLTI reactivity was directed against non-idiotypec cell surface determinants. Lymphoid cells from immunized mice demonstrated increased MLTI responses to cells of the immunizing tumor but not to other PCT, indicating that the post-immunization MLTI responses were primarily to individual rather than shared tumor cell surface antigens. Activity of both normal and immunized spleen cells was found to involve thymus-derived lymphocytes. The persistence of residual MLTI activity after treatment with anti-theta serum and complement, however, implicated participation of non-theta antigen-bearing cells in MLTI reactivity. From these data, we conclude that lymphoid cells from un-immunized mice are capable of T cell-dependent reactivity to syngeneic PCT-associated antigens and that elevations in these reactivities after immunization may reflect specific cellular immune responses.
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PMID:Stimulation of lymphoid cells from normal and immune mice by syngeneic BALB/c plasma cell tumors. 12 71

The presence of cell-free Ehrlich ascites tumor fluid in an appropriate concentration was shown to permit a proliferative response, strictly dependent on the presence of Thy-1-positive lymphocytes, to proceed when introduced on the initiation of mixed lymphocyte-tumor reaction of C57BL/6 lymphocytes and Mitomycin-C-treated C3H/He myeloma cells, while it clearly inhibited the development of cytotoxic killer T lymphocytes toward the priming allogeic tumor cells. The fluid had no effect, however, when added to normally primed spleen cells at the onset of cytotoxicity test. Further investigation of the mechanism in vitro by ascitic tumor fluid selectively suppresses the generation of killer T lymphocyte activity to allogeneic target cells may lead to a better understanding of the suppressed T-cell responses observed in Ehrlich tumor-bearing animals, and additionally, may provide an intriguing information about the interactions between the distinct T-cell subsets responsible for proliferative response and generation of killer T lymphocytes.
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PMID:Proliferative response of T lymphocytes to allogeneic tumor without generation of killer T lymphocytes in the presence of Ehrlich ascites tumor fluid. 13 60

Four examples of amyloid tumors were studied to determine whether there was an association with myelomatosis. Three patients had follow-up examinations of 12 years, 9 years, and 2 1/2 years, respectively. A local recurrence developed in one patient and a second lesion developed in this patient and in one other who also had a transient monoclonal 7S globulin peak. In spite of these findings, none of our patients developed myelomatosis. A study of the scanty literature on amyloid tumors reveals that only patients with lesions of the lung and urinary bladder have had long-term follow-up. They have invariably remained free of disease. Several reports of bone lesions have inferred that amyloid tumors occurring here signify solitary myeloma despite a lack of follow-up confirmation. Our longest surviving patient developed two bone lesions over a 12-year period without developing myelomatosis. Our findings lead us to conclude that there is little evidence to regard the presence of an amyloid tumor at any site as a manifestation of solitary myeloma or myelomatosis.
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PMID:Amyloid tumor. A clinicopathologic study of four cases. 14 47

A total of 45 cases of multiple myeloma has been followed up clinically during the period from 7 to 80 months. Out of these, six patients (13.3%) were diagnosed to be the tumor-forming type; they developed discrete tumor formation at the disease onset or during clinical observation. Biological behavior of these cases is briefly outlined. Histologically, five cases presented with well or moderately well differentiated plasma cells according to the grading made by Pasmantier and Azar. The remaining one case was poorly differentiated in cell maturity, and with electron and immunofluorescence microscopies, proved to be of plasmacytic nature.
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PMID:The tumor-forming type of multiple myeloma. I. Biological behavior. 16 Jan 83


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