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)

Cloned hybrid cells, selected for their ability to secret an IgG 2a immunoglobulin specific for single-stranded (ss) nucleic acids, were obtained by fusion of spleen cells from an unimmunized autoimmune MRL/1 pr male mouse with nonsecreting myeloma cells (MOPC-21, line Sp2/0-Ag 14). Designated MRss-1, this monoclonal antibody was (i) propagated by intraperitoneal injection of hybrid cells to pristane-treated. Balb/c mice, (ii) purified from the bulk of other proteins in ascites extracts by chromatography with DEAE-Sephacel adsorbent, and (iii) radiochemically labeled via reductive methylation using NaB3H4 and formaldehyde. The binding of 3H-labeled antibody to immobilized ssDNA- agarose, calf thymus) or soluble (fd DNA) ssDNA was rapid and dependent upon ssDNA and ionic strength, but not hydrogen ion concentration. Optimal binding occurred in both low and intermediate salt concentration (0.1-0.25 M NaCl), yet was completely abolished above 0.30 M NaCl. The presence of guanine (Gua)-containing mono-, oligo-, and polynucleotides also abolished and/or decreased 3H-labeled antibody binding to ssDNA-agarose. In these competition assays, the amount of Gua-containing mono-and oligonucleotides required to inhibit antibody binding by 50% (0.2-1.0 mg/mL) exceeded those of poly(G), rRNA, and fd DNA (i.e., 0.03-0.1 microgram/mL) by 4 orders of magnitude. In contrast, (deoxy)ribose 5'-phosphate as well as other nucleic acid derivatives devoid of Gua failed to inhibit antibody binding. The above findings were substantiated by the observation that 3H-labeled antibody bound to guanosine (G)- and guanidylate (pG)-conjugated Sepharose, yet not to other nucleoside (A, C, and U)- or nucleotide (pA, pC, and pU)-conjugated adsorbents. Last, the introduction of the methyl group at the N-2, O-6, and N-7 positions in the Gua ring system completely abolished antibody binding. Collectively, these results demonstrate that the MRss-1 antibody recognized single-stranded nucleic acid substrates by virtue of their content of guanidylate residues and, more specificity, by the presence of the Gua base moiety.
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PMID:Antibody-nucleic acid complexes. Identification of antigenic determinant of a murine monoclonal antibody specific for single-stranded nucleic acids. 617 38

A panel of hybridomas was constructed by fusion of P3X63Ag8 myeloma cells with spleen cells from a BALB/c mouse that had been immunized with a C57BL/Ka x-ray-induced lymphoma, C6XL. One of forty-three hybridomas secreting antibodies reactive with the tumor cells was found to be unreactive with normal spleen cells in a radioimmunometric assay. This antibody, designated 124-40, was unreactive with normal adult thymus, spleen, lymph node, or bone marrow cells, or with fetal spleen or thymus cells in radioimmunometric or radioimmunoprecipitation assays. Flow microfluorometric analysis of these nonmalignant lymphoid cells failed to reveal subpopulations reactive with MAb 124-40. The antibody was highly specific for the lymphoma cells used for immunization and did not react with a panel of other spontaneous or x-ray-induced or chemically induced lymphomas. The antigen reactive with MAb 124-40 was isolated by radioimmunoprecipitation and found to be a glycoprotein composed of disulfide-bonded subunits of 39,000 m.w. and 41,000 m.w. A cell surface component of similar structure, but not reactive with MAb 124-40 could be detected by two-dimensional electrophoresis in extracts of purified T cells, but not B cells. These results suggest that the apparently individually specific lymphoma antigen reactive with MAb 124-40 might be a clonally expressed epitope carried by a T cell surface component.
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PMID:Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. 1566 66

A monoclonal antibody against keratins (KL1) from normal human stratum corneum was obtained using hybridoma techniques. Spleen cells from immunized BALB/c mice were fused with NS1, a mouse myeloma cell line, to produce hybrids. Antibody activity to epidermal keratins was tested using an indirect immunofluorescence test on cryostat sections of human epidermis and rabbit lip. A stable clone producing antikeratin antibody was isolated and an ascitic fluid was produced and used as a source of antibody (IgG1 kappa). KL1 was characterized by its immunohistochemical staining of various epithelia and by its recognition of 55-57 kilodalton (kd) keratin polypeptide from normal epidermis using the immunoblot technique. Frozen and deparaffinized sections of normal human epidermis, mucosa, and esophagus were stained by this antibody only in the upper cell layers as demonstrated by both indirect immunofluorescence and immunoperoxidase techniques. Approximatively 80% of normal keratinocytes isolated after trypsinization were labeled by KL1 whereas most negative cells showed basement membrane zone antigens. This confirmed differences in the expression of medium-sized polypeptides between basal and supra-basal cells during the course of human epidermal differentiation. All epithelial cells from other human epithelia (thymus, thyroid, bronchial mucosa, stomach, intestines) were positive with KL1 whereas nonepithelial cells and tissues did not show any staining. In view of these results KL1 promises to be a useful tool in the exploration of human epithelial differentiation.
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PMID:Reactivity pattern of a monoclonal antikeratin antibody (KL1). 619 31

A hybridoma obtained between normal spleen cells from BALB/c mice (a non-autoimmune strain) and SP2-O-Ag 14 myeloma cell line was designated as HB2. These hybrid cells produced an IgM kappa-anti-ds-DNA antibody, but their specificity was limited to some polydeoxyribonucleotides such as natural ds-DNA from calf thymus, poly dG-poly dC, poly d(GC) and poly d(GC)-poly d(GC). In contrast, poly dA-poly dT, poly d(AT) were not recognized. The configuration of the nucleic acid helix plays a small role if any, in the building of the epitopes recognized by the hybridoma HB2 antibodies, while the presence of G and C appeared to be essential. These epitopes could not be found on ss- and ds-polyribonucleotides. B cells able to produce anti-ds-DNA antibodies are therefore present in non-autoimmune BALB/c mice, but not enough to produce the corresponding antibodies at a detectable level in the serum. Following immunization of BALB/c mice with hybridoma HB2 monoclonal antibodies, anti-idiotype antibodies were obtained which also recognized idiotopes present in the serum from both murine MRL/1 and human systemic lupus erythematosus (SLE).
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PMID:Generation of hybridoma antibodies to double-stranded DNA from non-autoimmune BALB/c strain: studies on anti-idiotype. 620 37

Investigations of human B-cell malignancies have generally focused on the monoclonal B-cell populations. Until recently there has been little emphasis on the thymus (T) lymphocyte in these disorders. Current studies, however, suggest that quantitative and qualitative disorders of T cells are generally seen both in chronic lymphocytic leukemia and in multiple myeloma. This review will focus on two major concepts. First, it will define the quantitative and functional T-cell abnormalities in B-cell malignancies including evidence suggesting a causal link between the T-cell abnormalities and certain observed disease manifestations in chronic lymphocytic leukemia and multiple myeloma. Secondly, it will review data demonstrating that these T cells may be influenced by in vivo and in vitro manipulations and will outline some of the possible resultant clinical effects.
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PMID:The influential T cell in B-cell neoplasms. 623 Apr 20

The major histocompatibility complex of the rat (RTl) is composed of at least five subregions. They are RTl-A,B,C,D and E regions. RTl-A,E and RTl-B,D regions encode class I and class II alloantigens, respectively. The RTl-C region encodes antigens which are similar to class I alloantigens and they are the homologue of mouse Qa-Tla antigens. A monoclonal antibody (X81-5C9) was produced against a rat B-cell leukemia, KNL-14. The KNL-14 cells were injected to a congenic rat, WKA. 1A(ACI). Spleen cells taken from the congenic rat were hybridized with mouse myeloma cell line P3.X63.Ag8.653. The monoclonal antibody lysed over 80% of nylon wool (N. W) adherent cells of lymph nodes, 25-30% of unseparated lymph node cells and/or spleen cells, and approximately 15-20% of peripheral blood lymphocytes of WKAH strain of rats. Only a portion (30-40%) of N. W. adherent cells of the peripheral blood lymphocytes was killed. Bone marrow cells, thymus cells and N. W. nonadherent cells were not lysed by the antibody. Macrophages, fetus, thymus and kidney homogenates could absorb the reactivity, whereas RBC, epidermal cells, brain, liver, testis could not absorb the cytotoxicity. A survey for the strain distribution of the antigen disclosed positive strains such as WKAH, W/Hok, LEJ, WKA. 1J (LEJ), ALB, WKA. 1B (ALB), BUF, BN, LEW, F344, W. 1L (F344) and KYN rats. The negative strains were NIG-III, WF, WKA. 1U WF), SDJ, W. 1U (SDJ), TO, W. 1T(TO), ACI, WKA. 1A(ACI), BDIX, WKA. 1DV1 (BDIX) and PVG/c rats. Immunochemically, the antibody precipitated antigens that gave two major bands on the SDS-PAGE. The heavy chain has an apparent molecular weight of 30 KD, which shifted to 33 KD under reducing conditions. The light chain has an apparent molecular weight of 12 KD. From these data a monoclonal antibody X81-5C9 is considered to detect a rat MHC (RTl) gene product which is different from the classic class I or class II cell surface antigens. It may be one of RTl-C antigens expressed mainly on B-cells. The characteristic feature of rat RTl-C antigens were discussed in relation to mouse Qa-Tla antigens.
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PMID:[A new B-cell alloantigen of the rat]. 623 70

Spleen cells from an SJL mouse immunized with B10.S spleen cells were fused with the nonsecretor myeloma line NS.1. One established hybrid cell line continuously secreted antibody that recognized a new antigenic specificity, tentatively called "Ly-m11." This newly found antigen is detectable on nearly 100 percent of spleen and lymph-node cells, 70 percent of bone-marrow cells, and 20 percent of thymus cells by direct cytotoxicity assays, and on the cells derived from kidney and liver. Strains that are Ly-m11 (+) include C57BL/6, C57BL/10J, B10.S, C57BR/cdJ, C57L/J, and C57BL/KsJ. Other mouse strains so far tested are Ly-m11 (-). The strain distribution pattern distinguished Ly-m11 from any known murine lymphocyte alloantigens, but it follows the H-3 alpha haplotype which is defined by skin transplantation. Linkage tests of nine congenic strains of H-3 and/or H-13/alpha loci and five recombinant inbred lines including CXB, BXH, AKXL, SWXL, and BXD revealed no recombinations between H-3 and Ly-m11 loci on chromosome 2. This newly discovered Ly-m11 alloantigen could itself constitute a minor histocompatibility antigen detectable by serological means.
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PMID:Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen. 624 82

A mouse helix-destabilizing protein (HD protein-1) has been purified and characterized, and controlled tryptic digestion has been used to generate two large fragments of this protein and to study structural changes accompanying DNA binding. HD protein-1, a DNA-binding protein that has higher affinity for single-stranded DNA (ssDNA)-cellulose than for double-stranded DNA (dsDNA)-cellulose and is resistant to a dextran sulfate elution from ssDNA-cellulose, was purified from mouse myeloma by the method described by Herrick and Alberts (Herrick, G., and Alberts, B. M. (1976) J. Biol. Chem. 251, 2124-2132). HD protein-1 was heterogeneous with regard to apparent molecular weight (range of Mr = 24,000 to 33,000), but individual Mr species shared extensive primary structure homology as revealed by tryptic peptide mapping. The predominant species of this protein, Mr = 27,000, was resolved from other species and obtained in nearly homogeneous form by preparative isoelectric focusing. Mouse HD protein-1 was capable of lowering the Tm of poly[d(A-T)] by 25 degrees C, indicating that it is a helix-destabilizing protein. Sedimentation boundary analysis revealed that binding to ssDNA was noncooperative and that the binding site covered about 6 nucleotide residues. There was a 35% increase in the intrinsic tryptophan fluorescence of the protein in the presence of ssDNA, suggesting that structural change accompanies binding. Subcellular localization studies indicated that 75% of mouse HD protein-1 is nuclear, but not chromatin-associated, and primary structure analysis indicated that HD protein-1 is distinct from high mobility group proteins 1 and 2, histones, and P8 protein. Tryptic hydrolysis of HD protein-1 produced discrete, large fragments whose apparent molecular weights ranged from 19,000 to 24,000, and whose relative abundance was changed by the presence of ssDNA during the digestion. Thus, a Mr = 22,000 fragment (22 HDP*) predominated in the absence of ssDNA, and a Mr = 19,000, fragment (19 HDP*) predominated in the presence of ssDNA. Poly(dT) and denatured calf thymus DNA were more effective than were other polynucleotides tested in promoting accumulation of 19 HDP*; (dT)8 was as effective as were longer molecules of (dT)n, but (dT)4 and (dT)6 were much less effective, indicating that the binding site involved in 19 HDP* accumulation covered between 6 and 8 residues of (dT)n. Both 19 HDP* and 22 HDP* have the same COOH-terminal end and the same affinity for ssDNA-cellulose as does the native HD protein-1, indicating that a Mr = 8,000 sequence at the NH2-terminal end of HD protein-1 is not required for binding to ssDNA. Even though 22 HDP* retained the ability to bind to ssDNA, it could not be converted to 19 HDP* by further trypsin digestion.
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PMID:Studies on the structure of mouse helix-destabilizing protein-1. DNA binding and controlled proteolysis with trypsin. 625 73

The antigenic relationships between human tumors of neuroectodermal origin and fetal brain were investigated by the production of hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells with splenocytes from a mouse multiply immunized with an homogenate of second-trimester human fetal brain tissue. Two monoclonal antibodies (MAs), 4D2cl 6 and 7H10cl 4, were studied in detail by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-anti-peroxidase (PAP) immunohistology. MA 4D2cl 6 binds to 5 of 14 glioblastoma (GBM) cell lines, 1 of 2 melanoma cell lines, 1 of 3 neuroblastoma cell lines, and 1 of 5 fetal fibroblast lines by CS-RIA and to 13 of 13 GBM, 1 neuroblastoma, and fetal brain, liver, spleen, and adult spleen unfixed frozen tissue by PAP analysis. MA 7H10cl 4 binds to 13 of 14 GBM, 1 of 3 neuroblastoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis and to 13 of 13 GBM, 1 neuroblastoma, fetal brain, liver, spleen, thymus, and adult spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue, including brain, were unreactive with both MAs by CS-RIA, PAP, and absorption analysis. Tissue distribution and localization analyses established that MAs 4D2cl 6 and 7H10cl 4 recognize specificities of shared fetal-neuroectodermal-lymphoid distribution which are operationally specific within the adult central nervous system and which are not related to previously described oncofetal or onconeural antigens.
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PMID:Expression of human fetal brain antigens by human tumors of neuroectodermal origin as defined by monoclonal antibodies. 627 12

The antigenic relationship between human tumors of neuroectodermal origin and fetal brain were further investigated by characterization of two hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NSI) myeloma cells and splenocytes hyperimmunized to second trimester human fetal brain homogenate. Monoclonal antibodies (MAs) 1H8cl 2 and 1H8cl 3 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-antiperoxidase (PAP) immunohistology. MA 1H8cl 3 is the more broadly reactive, binding to 9/14 glioblastoma (GBM), 2/3 neuroblastoma, 1/2 melanoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis, and to 12/15 GBM, fetal brain, spleen, and liver, and adult spleen by PAP analysis. MA 1H8cl 2 is more restricted, binding to 7/14 GBM, 2/3 neuroblastoma, 1 medulloblastoma, and 2/3 fetal skin fibroblast cell line(s) by CS-RIA, and to 9/15 GBM and fetal brain and spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue including brain, thymus, lymph node, liver, kidney, lung, skin, and pancreas, were unreactive with both 1H8cl 2 and 1H8cl 3 by CS-RIA, PAP, and absorption analysis. The data presented here establish the unique nature of the detected antigenic specificities as compared to previously described oncofetal and onconeural antigens, and define two immune reagents which are operationally specific for tumors of neuroectodermal origin within the adult central nervous system.
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PMID:Human fetal brain antigen expression common to tumors of neuroectodermal tissue origin. 628 96


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