Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA synthesis in mouse myeloma (MPC-11) cells and L cells was rapidly and progressively inhibited by infection with vesicular stomatitis virus (VSV). No significant difference in cellular DNA synthesis inhibition was noted between synchronized and unsynchronized cells, nor did synchronized cells vary in their susceptibility to VSV infection after release from successive thymidine and hydroxyurea blocks. Cellular RNA synthesis was inhibited to about the same extent as DNA synthesis, but cellular protein synthesis was less affected by VSV at the same multiplicity of infection. The effect of VSV on cellular DNA synthesis could not be attributed to degradation of existing DNA or to decreased uptake of deoxynucleoside triphosphates, nor were DNA polymerase and thymidine kinase activities significantly different in VSV-infected and uninfected cell extracts. Analysis by alkaline sucrose gradients of DNA in pulse-labeled uninfected and VSV-infected cells indicated that VSV infection did not appear to influence DNA chain elongation. Cellular DNA synthesis was not significantly inhibited by infection with the VSV polymerase mutant tsG114(I) at the restrictive temperature or by infection with defective-interfering VSV DI-011 (5' end of the genome), but DI-HR-LT (3' end of genome) exhibited initially rapid but not prolonged inhibition of MPC-11 cell DNA synthesis. DNA synthesis inhibitory activity of wild-type VSV was only slowly and partially inactivated by very large doses of UV irradiation. These data suggest that, as in the effect of VSV on cellular RNA synthesis (Weck et al., J. Virol. 30:746-753, 1979), inhibition of cellular DNA synthesis by VSV requires transcription of a small segment of the viral genome.
 ...
PMID:Inhibition of cellular DNA synthesis by vesicular stomatitis virus. 616 31

Hybrid cell lines were established from fusions between lipopolysaccharide- (LPS) stimulated C57BL/6J spleen cells and MPC-11 tumor cells (45.6TG1.7, abbreviated M45), and were tested for their ability to immunize semiallogeneic mice against a parental tumor challenge. These hybrids were tumorigenic in syngeneic (BALB/c X C57BL/6J) F1 (CB6F1) mice but did not grow in semiallogeneic (BALB/c X A/J) F1 (CAF1) mice. All hybrids express both parental major histocompatibility antigens (H-2b and H-2d) as detected by indirect immunofluorescence and by their ability to function as either stimulators or targets for allogeneic cytotoxic lymphocytes (CTL). M45 tumor-associated antigens (TAA) were expressed on the hybrid surface as shown by their ability to act as either stimulators or targets for syngeneic CTL specific for M45 TAA. Immunization of semiallogeneic CAF1 mice with the hybrids i.p. followed by a challenge with M45 tumor cells resulted in extended survival when compared to untreated mice or animals immunized i.p. with M45 tumor cells. This immunity was specific and was not due to an allogeneic effect; immunization with an unrelated H-2bd tumor, 70Z/3, or H-2bd B6D2F1 spleen cells or with semiallogeneic spleen cells plus M45 did not protect mice from M45 challenge. Interestingly, prophylactic priming with semiallogeneic hybrid tumor cells or parental myeloma cells led to M45-specific CTL and "help" for an in vitro CTL response; however, the degree of CTL priming by hybrid tumors was not augmented when compared to the level of CTL achieved with parental tumor alone. Hence, stimulation of CTL activity per se by hybrid tumor cells cannot explain the protective effect of hybrid tumor immunization. These studies nevertheless confirm that semiallogeneic hybrids, which we show express TAA and alloantigens, can be used to immunize mice against a lethal syngeneic myeloma tumor challenge.
 ...
PMID:Augmentation of syngeneic tumor-specific immunity by semiallogeneic cell hybrids. 618 10

The La antigen recognized by certain lupus erythematosus autoantibodies was found to be predominantly associated with 7 S RNA in baby hamster kidney cells and human Raji cells, but not in HeLa cells where mainly the 7-2 RNA was associated with the La protein. In mouse myeloma cells (MPC-11) and mouse lymphoma cells (WEHI) that secrete immunoglobulins, equal amounts of 7 S and 7-2 RNAs were present in anti-La immunoprecipitates. The highly conserved 7 S RNA is a component of the signal recognition particle involved in protein secretion (Walter, P., and Blobel, G. (1982) Nature (Lond.) 299, 691-698), and its association with the La antigen appeared to be cell-type specific. Thus, it is possible that the La-7 S RNA association correlates with the abundance of 7 S RNA or with the secretory activity of the cell type.
 ...
PMID:Association between the 7 S RNA and the lupus La protein varies among cell types. 619 54

The expression of two kappa light chain immunoglobulins in the MPC-11 mouse myeloma is well established, the two protein products being apparently from RNA transcripts derived from separate, rearranged kappa alleles in the MPC-11 genome. Recently, the characterization of kappa-related RNAs and protein products in several lambda-producing myelomas has indicated that multiple expression of light chain RNAs is a common event in myelomas and other cells of the B-lymphocyte lineage. These studies suggest that, although many light chain alleles may function to make RNA and protein in a given B-lymphocytic cell, only one complete, functional light chain is generally translated from the RNAs present in a single cell. The myeloma, MOPC-315, synthesizes and secretes an antibody which has an alpha heavy chain and a lambda II light chain. The DNA of MOPC-315 either has no kappa genes or has only a fragment of one, but it certainly has no kappa genes in the embryonic configuration. Rearrangement of its lambda genes has been observed but the exact nature of the rearrangement is not known. Because initial observations suggested that an immunoglobulin-related protein other than alpha and lambda II was present in MOPC-315 cells, we undertook to derive molecular cDNA clones from the MRNA in MOPC-315 tumour cells. Analysis of the clones has now identified two lambda chain mRNA species: a normal lambda II chain mRNA and another which directs the synthesis of a deleted form of a lambda I protein. The nucleotide sequence of the deleted lambda I mRNA shows that it resulted from a joining of the sequence encoding amino acid 31 of the variable region directly to the constant region coding sequence.
 ...
PMID:Dual expression of lambda genes in the MOPC-315 plasmacytoma. 625 34

During B lymphocytes differentiation, switches in the expression of heavy chain immunoglobulin constant region (CH) genes occur by a novel DNA recombination mechanism. We have investigated the requirements of the CH gene switch by characterizing two rearranged gamma 2b genes from a gamma 2b producing mouse myeloma (MPC-11). One of the two gamma 2b genes is present in 2-3 copies per cell (gamma 2b strong hybridizer) while the other is present in approximately 1 copy per cell (gamma 2b weak hybridizer). Genomic clones of the gamma 2b strongly hybridizing gene indicate that this is an abortive switch event between the S gamma 3 and S gamma 2b regions. However, clones of the gamma 2b weakly hybridizing gene suggest a functional rearrangement due to the presence of VH, JH and S mu sequences. The switch-recombination sites of these rearranged gamma 2b genes and those of other CH genes show a high degree of preference for the sequence AGGTTG 5' of either the S mu donor site or the appropriate CH S acceptor site. AGGTTG and its analogs are rare in the S mu region, are somewhat prevalent in s alpha and in the case of S mu are found 5' of a tandemly repeated DNA sequence (GAGCT, GGGGT) comprising most of S mu.
 ...
PMID:On immunoglobulin heavy chain gene switching: two gamma 2b genes are rearranged via switch sequences in MPC-11 cells but only one is expressed. 627 24

A variant line (LV-1) of mouse myeloma MOPC 315 (IgA, lambda 2) has lost the ability to synthesize L chain. It synthesizes an altered H chain (H' chain) that is turned over intracellularly and is not secreted. Rescue of H' chain secretion can be accomplished by fusion of LV-1 to a variant of another myeloma line, MPC 11 (IgG2b, kappa), which only synthesizes a light chain. The hybrid (X-2) secretes the H' chain in a four chain structure (kappa 2 alpha' 2). In wild-type MOPC 315 cells, it was reported previously that inhibition of core sugar addition blocks the secretion of the H chain polypeptide. We have studied glycosylation in MPOC 315 wild-type, LV-1 variant, and X-2 hybrid cell lines. The ability of all three lines to add the core sugars mannose and glucosamine to heavy chain was demonstrated. Due to the instability of the H' chain in LV-1, it is difficult to assess H' chain fucosylation directly. To study fucose addition in LV-1, the enveloped virus vesicular stomatitis (VSV), which can infect the three lines, was utilized. The fucosylation and secretion of VSV glycoprotein G was discernible in all three lines; however, only LV-1 cannot activate free fucose, and instead fucosylates through conversion of the mannose intermediate. Normal fucose addition to H chain in a wild-type cell occurred immediately before secretion. The fact that degradation of H' chain in LV-1 begins before fucosylation suggests that the rescue of H' chain secretion by formation of the X-2 hybrid is due to the acquired presence of a suitable L chain rather than complementation of a sugar defect. These observations indicate that proper assembly of the polypeptide components of some secretory proteins, e.g., Ig molecules, is required for the secretion of the individual chains.
 ...
PMID:Glycosylation and secretion of an altered immunoglobulin heavy chain in mouse myeloma MOPC 315. 629 92

In an attempt to separate malignant from normal and reactive stromal cells, we fractionated ascites cells from BALB/c mice bearing a transplantable myeloma (MPC-11) by isopyknic centrifugation in continuous density gradients of povidone-coated silica gels (Percoll). Cells from different fractions were then analyzed by morphologic and immunologic criteria. The ability of cells from the different fractions to form colonies in soft agar and to produce tumors in BALB/c mice was also examined. Although most fractions contained morphologically identifiable plasma cells, colony-forming cells (CFC), derived from multiply passaged tumors, separated in a sharp peak at 1.072 g/ml. CFC peaked at 1.078-1.082 g/ml for tumors passed less than three times and were invariably markedly depleted from the low-density portions of the gradients. Cells recovered from different fractions of the gradients were cultured in soft agar and inoculated sc into syngeneic mice. In these experiments, a highly significant correlation was observed between the ability of cells to form colonies in soft agar and to form tumors in vivo. This correlation suggests that CFC and tumorigenic cells have similar distributions.
 ...
PMID:Separation on Percoll density gradients of cells derived from malignant ascites of mice. 629 17

The expressed immunoglobulin heavy chain genes of five gamma 2b-gamma 2a hybrid chain-producing variants of the mouse myeloma MPC-11 (gamma 2b, kappa) have been characterized by genomic Southern blot analysis. Results show that a hybrid gamma 2b-gamma 2a gene was formed in each variant by recombination between the expressed gamma 2b gene of MPC-11 and a gamma 2a gene. The recombination sites are within regions of marked homology between gamma 2b and gamma 2a genes: at least three and probably four variants show gamma 2b-gamma 2a recombination within the heavy chain constant region 2 (CH2) domain, while the fifth has its recombination site between the penultimate nucleotide of CH1 and the eighth nucleotide of the hinge. An unexpected finding is that the hybrid heavy chain-producing variants fall into two subgroups based on their use of different gamma 2a gene forms in hybrid gene formation. This result leads to the speculation that either a tandem gamma 2a gene duplication was present in MPC-11 prior to variant generation or mitotic recombination between chromosomes occurred in the generation of one variant subgroup. The similarity of hybrid gene formation in MPC-11 variants to that apparently responsible for concerted evolution within multigene families and hybrid protein expression in various individuals is noted, and the possible relationship between hybrid gene formation and the heavy chain class switch is discussed.
 ...
PMID:Hybrid gamma 2b-gamma 2a genes expressed in myeloma variants: evidence for homologous recombination. 631 38

A total of 53 different cell lines originating from a variety of mammalian species were cultured in vitro and analysed for the presence of vimentin, employing polyacrylamide gradient slab gel electrophoresis in urea/acetic acid as buffer system. Irrespective of the cell culture conditions, and the growth potential and morphology of the cells, vimentin was expressed in all cell lines examined, with two exceptions: MPC-11 mouse myeloma and MOPC-31C mouse plasmacytoma cells. Immunoblotting with the monoclonal antibody alpha-IFA, which is directed against an antigenic determinant shared by all classes of intermediate filaments, did not detect any other of the known intermediate filament proteins in MPC-11 and MOPC-31C cells. Vimentin synthesized by various cell lines was characterized by four different criteria: (1) its extractability with Triton X-100 under various ionic conditions; (2) its behaviour in (NH4)2SO4 fractionation of cellular extracts; (3) its electrophoretic mobility in polyacrylamide gel electrophoresis in urea/acetic acid; and (4) the co-isolation of polypeptides of higher electrophoretic mobility, which, by comparison with degradation products of vimentin obtained with the Ca2+-activated proteinase specific for intermediate filament proteins in vitro, were identified as products of Ca2+-dependent proteolysis of vimentin. Although the degradation products occurred in different ratios in extracts of different cell lines, they constituted the same characteristic set of proteins whenever degradation of vimentin was observed. The formation of proteolytic breakdown products could be partially to totally suppressed when the cells were harvested, washed and processed in the presence of EGTA and proteinase inhibitors. The experimental data show that: (1) vimentin, as well as the Ca2+-activated proteinase specific for intermediate filament proteins, is highly conserved during the evolution of mammalian species; (2) the proteolytic breakdown products of vimentin, which give rise to a characteristic 'staircase' in two-dimensional gel electrophoresis, are probably artefacts of isolation; (3) the expression of vimentin is neither a prerequisite for nor necessarily indicative of rapid cell proliferation in vitro; and (4) the techniques described can be used for the routine identification of vimentin in cells and tissues in case vimentin-specific antibodies are not available.
 ...
PMID:Polyacrylamide gel electrophoretic screening of mammalian cells cultured in vitro for the presence of the intermediate filament protein vimentin. 641 17

Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the CH3 domain. The CH3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H2L2 moieties in contrast to MPC 11, which secretes only H2L2 . The heavy chains of HL apparently contain more carbohydrate (CHO+) than do the H chains of H2L2 , and inhibition of N-linked glycosylation results in the secretion of relatively more H2L2 . Here we present evidence suggesting that (a) the absence of the CH3 domain has led to conformational changes in these molecules, (b) these changes permit posttranslational glycosylation, and (c) unrestrained glycosylation can frequently yield unusual CHO+ structures that make complete assembly unlikely.
 ...
PMID:Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly. 642 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>