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)

One of six transplantable ascites tumors of BALB/c mice was found to become periodically resistant to cytotoxic T lymphocytes (CTL). About 12 days after LPC-1, a myeloma tumor, was transplanted it became resistant to lysis by allogenic CTL (anti-H-2d) and by CTL directed to trinitrophenyl groups or minor histocompatibility antigens. Susceptibility to lysis by all of these CTL was regained within 2 to 4 days after transfer of resistant cells to a fresh BALB/c host. These changes were recurrent: in each transplantation cycle the early LPC-1 cells were susceptible and the late cells were resistant to CTL. Analyses with antisera (B10 anti-B10.D2) showed that the serologically recognized products of the H-2d haplotype were reduced about 10-fold on the LPC-1 cells that were resistant to CTL.
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PMID:Cyclical changes in susceptibility of a myeloma tumor (LPC-1) to immune destruction. I. Changes in reactivity with cytotoxic T lymphocytes and anti-H-2d sera. 31 28

A newly discovered genetic marker in the kappa light chains of mouse immunoglobulins is described. This marker, designated kappa-PC8, is located in the L chains of those anti-phosphorylcholine (PC) antibodies which show the same functional and idiotypic characteristics as a PC-binding myeloma protein, HOPC 8 (H8). Analytical isoelectric focusing of these L chains revealed two phenotypes whose strain distribution pattern suggested a genetic association with genes that determine the T lymphocyte surface antigen(s) Ly-2/Ly-3. In four strains , AKR/J, C58/J, RF/J and PL/J (AKR-type, A) the H8-like L chains have a slightly lower isoelectric point than those of C57L/J and 12 other strains (C57L-type, B). Breeding experiments showed that the kappa-PC8-A phenotype is preferentially expressed. The most probable location of the marker is the variable region since other idiotypically related kappa-chains in C57L/J and AKR/J do not show differences in their electrophoretic mobility.
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PMID:Genetic marker in the variable region of kappa chains of mouse anti-phosphorylcholine antibodies. 82 99

The cellular basis of the antibody-mediated, hapten-specific anti-idiotype antibody response of CBA/J mice to a hapten conjugate of the BALB/c myeloma protein LPC-1 was examined. Previous studies have shown that anti-idiotype antibody is produced if the mice are given anti-2,4-dinitrophenyl (DNP) antibody and then immunized with DNP-LPC-1; immunization with DNP-LPC-1 or LPC-1 alone does not lead to the production of this antibody. In the present experiments, mice depleted of thymus-derived lymphocytes by two different techniques failed to make anti-idiotype antibody after transfer of anti-DNP antibody and immunization with DNP-LPC-1. However, thymus-deprived mice given anti-DNP antibody and reconstituted with thymus-derived spleen cells did make anti-idiotype antibody in response to DNP-LPC-1. Thymocytes could not reconstitute such mice for this response. The possible mechanisms for this hapten-specific, antibody-mediated, T cell-dependent helper effect are discussed. It is felt that such helper effects represent an alternate pathway to conventional specific T cell-mediated cooperation. Further examples of antibody-mediated helper effects which support this hypothesis are also presented.
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PMID:The role of thymus-derived lymphocytes in an antibody-mediated hapten-specific helper effect. 108 13

Antiidiotypic antisera to LPC-1 and MOPC-300 plasmacytoma globulins were produced in rabbits by immunization with the corresponding antigen and exhaustive immunoabsorption with normal BALB/c plasma and other myeloma globulins. IgG fractions of these antisera when given intraperitoneally on three consecutive days after tumor implantation, protected the animal specifically from the grafting of the corresponding plasmacytoma or induced regression of the tumors after their initial grafting and growth. In vitro cytotoxicity of the antisera to plasmacytoma cells was not demonstrated. Plasma of the antisera-treated normal BALB/c mice, though containing antiidiotypic antibody in high titers (320-640), was not cytotoxic to tumor cells. The inhibitory effect on tumor growth can be considered the result of passive immunization against plasmacytoma with xenogeneic humoral antibody.
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PMID:Passive immunity to murine plasmacytoma by rabbit antiidiotypic antibody to myeloma protein. 125 Aug 37

BALB/c mice with the plasmacytoma MOPC 104E producing monoclonal IgM-lambda with antibody activity to alpha-1,3 dextran were found to have B lymphocytes with surface immunoglobulins with the immunochemical characteristics of 104E IgM capable of binding alpha-1,3 dextran. RNA extracted from this plasmacytoma induced the synthesis of such surface immunoglobulins on normal B lymphocytes in vitro and in vivo. Injection of 200 mug of MOPC 104E RNA into normal mice 72 hr prior to the administration of the antigen kept the immune response to dextran-S intact, but suppressed that to other antigens, such as DNP-Ficoll and LPS, T cell-independent antigens, and SRBC and BSA which are T cell-dependent. The effect of the RNA was abolished by RNase but not by pronase and DNase. RNA extracted from LPC-1 tumour (gamma2a-k without known antibody activity) significantly suppressed the immune response to dextran-S and to other antigens in normal mice. Thus, opposite effects of MOPC 104E RNA on the response to specific and non-specific antigens strengthen the hypothesis that the immune deficiency in plasmacytoma bearing mice is due to the conversion of normal surface immunoglobulin of a population of B lymphocytes to the idiotype of the respective myeloma globulin.
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PMID:Surface immunoglobulins of lymphocytes in plasmacytoma. V. The effect of RNA-rich extract from mouse plasmacytoma MOPC 104E on the immune response. 127 83

Two mice DBA/1 were each immunized with a single injection of one million enriched parietal cells in the hind foot pads. Monoclonal antibodies to be used as research tools in studies on regulatory mechanisms in gastric parietal cells were obtained after fusion of mouse myeloma cells (SP2) with cells from the popliteal lymph nodes of the mice. Twelve hybridomas produced antibodies reactive with structures only present in parietal cells as assessed by immunohistochemistry of oxyntic mucosa sections. Three hybridomas were subcloned and the antibodies produced by them, designated as PC4, PC8, and PC117, were characterized. In an enzyme-linked immunosorbent assay, all antibodies reacted with H,K-ATPase-containing vesicles. The antibody PC8 recognized a 94 kDa protein after immunoblotting of H,K-ATPase-containing vesicles and all antibodies precipitated a 94 kDa protein from [125I]H,K-ATPase-containing vesicles. The antibodies PC4 and PC117 recognized extracellular structures with a polarized distribution in viable, purified parietal cells. The results suggest that the structure recognized by all three antibodies is the alpha-subunit of the H,K-ATPase. The antibodies produced by another hybridoma, PC43, recognized a structure present in parietal and surface epithelial cells of the oxyntic mucosa. In an enzyme-linked immunosorbent assay, they reacted with a high-activity carbonic anhydrase which had been affinity-purified from pig oxyntic mucosa and they recognized a 30 kDa protein after immunoblotting. Thus, monoclonal antibodies against both intracellular and extracellular parietal cell structures were obtained after immunization with a small number of parietal cells.
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PMID:Production of monoclonal antibodies against gastric parietal cell antigens. 131 14

Several lines of evidence suggest that immunoglobulin (Ig) light (L) chain plays a role in the secretion of heavy (H) chain. For example, myeloma variant lines, which synthesize the Ig H chain but not the L chain, fail to secrete H chain protein. Here we have tested directly the role of chain assembly in the control of Ig secretion by the transfer of functional L chain genes into two such L chain-defective myeloma mutants. A lambda 2 or kappa L chain gene was introduced into variant lines of the mouse myelomas MOPC 315 (IgA, lambda 2) or PC7 (IgM, kappa), respectively. Although the two mutant lines are unable to secrete the H chain they produce, rescue of secretion of complete Ig protein molecules (IgA or IgM) was observed after transfection. These results imply that the secretory apparatus of these cells is intact and that the failure to secrete free H chain reflects a structural feature intrinsic to that protein. The implications of these results with respect to control of secretion of multi-subunit proteins are discussed.
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PMID:Gene transfer of immunoglobulin light chain restores heavy chain secretion. 309 73

We have analyzed the expression of cyclophosphamide (CY) resistance in somatic cell hybrids of mouse LPC-1/CY-R plasmacytoma and P3-X63-Ag8.653 (Ag8) myeloma cells. LPC-1/CY-R tumor is resistant to curative doses (60-250 mg/kg body weight) of CY. The median survival time (MST) of drug treated LPC-1/CY-R tumor bearing mice is 25 days, similar to that of untreated mice. LPC-1/CY-R tumor cells secrete an IgG 2a kappa M component and do not survive in tissue culture. Ag8 tumor cells are CY sensitive, are selected out in hypoxanthine-aminopterin-thymidine (HAT) media and do not secrete any immunoglobulin. Hybrids formed between these two cell lines survived in HAT and secreted IgG 2a kappa. Hybrid cells exhibited greater ploidy than that of their parents and contained the metacentric marker chromosome of the Ag8 cell line. Hybrid cells exhibited the same growth characteristics in BALB/c mice as that of their LPC-1/CY-R parent and were resistant to curative doses of CY. These studies demonstrate that, CY resistance is a somatic cell dominant trait which can be transferred to daughter cells via somatic cell hybridization. Availability of somatic cell hybrids produced between CY sensitive and resistant tumor cells may provide useful tools to study the biochemical nature and the somatic cell genetics of this drug resistant trait.
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PMID:Phenotypic cyclophosphamide resistance in mouse myeloma hybridomas. 316 7

Mixtures of BALB/c bone marrow (5 X 10(6) and LPC-1 myeloma (2 X 10(6) cells have been purged in vitro with 100 microM 4-hydroperoxycyclophosphamide (4HC) for 30 min at 37 degrees C. Elimination of tumor cells was assessed by monitoring newly synthesized tumor-specific IgG 2a kappa in vitro and by reinjecting the cells subcutaneously into the hindlegs of mice. Drug-treated LPC-1 cells had no detectable tumor production and did not reproduce tumors. Untreated cells regrew as solid tumors and killed the host within 3-4 weeks. Bone marrow cell suspensions purged of tumor cells were then used to reconstitute lethally pretreated mice injected 24 h earlier with 300 mg/kg cyclophosphamide (CY). Mice injected with CY alone died within 10 days. Those reconstituted with bone marrow cells or with purged bone marrow-tumor cell mixture lived longer than 7 months. Mice reconstituted with untreated bone marrow-tumor cell suspension grew tumors, had detectable tumor-specific IgG 2a kappa in their serum, and died by day 44. These studies demonstrate that the success of myeloma cell purging can be determined by monitoring newly secreted tumor protein and that 4HC successfully eliminates malignant plasma cells in vitro without impairment of normal bone marrow stem cell functions.
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PMID:Detection of residual murine LPC-1 myeloma cells from bone marrow cell mixture after purging by 4-hydroperoxycyclophosphamide. 329 61

The murine BALB/c myeloma LPC-1 demonstrates a periodic resistance to lysis by immune mechanisms; this correlates with the production and accumulation of a trypsin-sensitive, single chain glycoprotein of 160 kilodaltons gp160 on the tumor cell surface. Tumor cells obtained 4 days after transplantation are lysed by cytotoxic T lymphocytes whereas ten-day cells are resistant to lysis. The progressive resistance to lysis was correlated with an increasing amount of gp160 on the surface of LPC-1 cells. Cell surface morphology, as determined by scanning electron microscopy, showed that early cells consisted of equal proportions of cells having microvilli or ruffles. The late cell population consisted mainly of cells with microvilli. These microvilli were twice as abundant on late LPC-1 cells as on early cells. Transmission electron microscopy images of late LPC-1 cells suggested an active protein synthesis which correlated with a more intense deposition of ruthenium red and an increasing amount of gp160 on the cell surface.
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PMID:Morphology surface of a mouse plasmacytoma (LPC-1) showing cyclic resistance to immune lysis. 348 27


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