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)

BALB/c mice were immunized with human lymphoblastoid cells (RPMI 8866 cells) expressing surface receptors for IgE (Fc epsilon R). Spleen cells from animals displaying high titres of anti-Fc epsilon R antibodies were fused with HGPRT-deficient NSI myeloma cells. Anti-Fc epsilon R antibodies were identified by a flow cytometric assay based on their ability to block the binding of IgE-coated fluorescent latex particles to Fc epsilon R-positive cells. Fourteen monoclonal hybridoma cell lines secreting antibody of the required specificity were amplified in tissue culture and then grown in the peritoneal cavity of BALB/c mice in order to obtain ascitic fluids with high antibody titres. The specificity of each monoclonal antibody (Mab) to lymphocyte Fc epsilon R was shown by the following observations: (i) the intact monoclonal antibody molecule or, in some cases, its F(ab')2 fragments blocked the binding of IgE to several Fc epsilon R(+) cell lines different from that employed for the initial immunization; (ii) the Mab bound directly to all the Fc epsilon R(+) cell lines tested, but not to several Fc epsilon R(-) cells as determined by indirect immunofluorescence; (iii) the binding of Mab to Fc epsilon R(+) cells was selectively blocked by IgE, but not by the other classes of Ig; and (iv) Mab had no effect on the binding of IgG to Fc gamma R on normal human peripheral blood mononuclear cells (PBMC).
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PMID:Detection and characterization of monoclonal antibodies specific to IgE receptors on human lymphocytes by flow cytometry. 316 Jun 55

Human-human B-cell hybridomas were established using peripheral blood lymphocytes from patients with autoimmune thyroiditis and Graves' disease. Peripheral mononuclear cells (PMC), with or without mitogen prestimulation, were fused with HGPRT-negative human myeloma cell lines (Gm4672 and GM0462) using 44% polyethylene glycol. Developing hybridomas were screened by enzyme-linked immunosorbent assays (ELISAs) for human IgG and IgM and antibodies to human thyroglobulin (hTg) and microsomal antigen (M-Ag). A 125I-TSH binding inhibition assay was utilized for detecting antibodies to TSH receptor (TSH-R) protein. Hybridoma formation was observed only after prior mitogen stimulation of PMC. The amount of antibody secreted by the human-human hybridomas was highly variable (10 ng-100 micrograms/ml IgG/IgM). Nine and six-tenths percent of the hybrids secreted anti-hTg and 8.4% secreted anti-M-Ag. A 5% cloning efficiency was achieved, with detection of specific thyroid autoantibody secretion in one-third of the clones derived from positive hybridomas. Immunoglobulin secretion decreased with time and long-term stable clones were not achieved. Thyroid monoclonal autoantibodies to hTg, M-Ag, and TSH-R (IgG and IgM) detected during these studies were of a low affinity. In addition, antibodies were identified which exhibited marked specificity crossover between hTg, M-Ag, and nonthyroid antigens, suggesting the presence of recurrent epitopes. Such observations may help explain the multiplicity of thyroid autoantibodies in human thyroid disease and indicate a common defect in immunoregulation. We suggest that cross-reacting epitopes may be important in the derivation of thyroid-specific B-cell clones.
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PMID:A study of human-human hybridomas from patients with autoimmune thyroid disease. 355 36

Mouse monoclonal antibodies to various human epidermal and basement membrane components were formed by immunizing Balb/c mice with ME-180, a line of human cervical carcinoma cells. The spleen cells from hyperimmunized mice were fused with a nonsecreting mouse myeloma cell line using polyethylene glycol. The resulting hybrids were selected by growth in media containing 20% fetal calf serum, hypoxanthine, thymidine, and methotrexate in RPMI-1640 in 24-well Linbro plates. Wells producing antibodies of interest were grown and eventually cloned over an HGPRT- rat fibroblast feeder layer. These cultures were expanded and recloned. Two cloned antibodies of interest are DUX 5.2 and DUX 1.1.3. DUX 5.2 is the mouse IgG1 subclass and reacts with the membranes of ME-180 cells and the human skin epidermal basement membrane zone as shown by direct immunofluorescent microscopy. Ultrastructural localization using electron microscopic immunoperoxidase techniques showed localization of the DUX 5.2 antigen to be beneath the lamina densa; the reaction product may include the anchoring fibrils. Although DUX 5.2 reacts with the normal human basement membrane zone and the basement membrane zone in several diseases, there is no reactivity in the normal, never-blistered skin of patients with dystrophic epidermolysis bullosa (DEB). This suggests that the increased collagenase in the disease may be destroying antigenicity of the antigen recognized by DUX 5.2 or that the antigen may not be present in DEB. This antibody will thus allow early neonatal and prenatal diagnosis in DEB and allow isolation of the structural moiety which is deficient in DEB. DUX 1.1 is an IgM mouse immunoglobulin specific for the cytoplasm of human basal cells. Its reactivity with upper epidermis is significantly less than that seen in the basal layer. All cells of the basal layer stain uniformly. The slight amount of staining in upper cells probably represents dilution of antigen which is not synthesized beyond the basal layer. Basal cells of hair follicles and sweat glands are stained to some degree.
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PMID:Monoclonal antibodies to normal and abnormal epithelial antigens. 619 49

Hybridomas were made between NS1/1-Ag4-1 mouse myeloma cells and spleen and lymph node cells from a sheep immunized with sheep red cells (RBC). The hybrid colonies grew well in culture but there was a substantial loss of sheep chromosomes. No hemolytic or agglutinating antibodies were detected in the culture supernatants after the 17th day following fusion, but immunofluorescence tests indicated that a few of the cells may have been expressing sheep IgG. Cytogenetic comparison of cells grown with and without HAT medium provided evidence that the enzyme HGPRT is located on the X chromosome of sheep as it is in man and mouse. Hybridoma isozyme patterns of esterase, G6PD, 6PGD, NP, LDH and SOD tested between the 63rd and 71st day of culture were like those of NS1; NP and LDH also showed zones that probably came from the sheep component.
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PMID:Culture of sheep X mouse hybridoma cells in vitro. 682 96

Somatic cell hybrids were prepared between the TK-deficient variant of murine pre-B cell line, 70Z/3, cells and the HGPRT-deficient variant of non-secreting myeloma cells. Several hybrid clones which secreted IgM but did not express surface IgM were isolated. LPS stimulation did not induce the expression of surface IgM. SDS-PAGE analysis indicated that the IgM secreted by one of the hybrid clones was a 19S pentamer and that the size of its mu-chains was the same as that of mu-chains from MOPC 104E myeloma IgM. Two-dimensional gel electrophoresis of biosynthetically labeled immunoglobulin showed that the same pattern was obtained with kappa-chains from two hybrid clones and from the LPS-induced 70Z/3 cells. The result showed that cell hybridization could induce L-chain synthesis in the pre-B cell line. Anti-idiotypic antibody against the secreted IgM was prepared and it was shown that the surface IgM expressed on all LPS-stimulated 70Z/3 cells bore the same idiotype. Those results indicated that the specificity commitment has already occurred in 70Z/3 cells.
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PMID:Induction of 19S IgM secretion in a murine pre-B cell line, 70Z/3, by cell hybridization with non-secreting myeloma cells. 698 54

Uric acid is the end-product of purine nucleotide metabolism in man. The renal handling of urate is a complicated process, resulting in a fractional clearance of 8.2-10.3%. The anhydrous form is thermodynamically the most stable uric acid crystal. Uric acid is a weak acid that ionizes with a Pka at pH 5.75. At the normal acidic region, uric acid solubility is strongly increased by urinary pH. The prevalence of uric acid stones varies between countries, reflecting climatic, dietary, and ethnical differences, ranging from 2.1% (in Texas) to 37.7% (in Iran). The risk for uric acid stone formation correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. Hyperuricosuria is the major risk factor, the most common cause being increased purine intake in the diet. Acquired and hereditary diseases accompanied by hyperuricosuria and stone disease include: gout, in strong correlation with the amount of uric acid excreted, myelo- and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia and hemolytic disorders, hemoglobinopathies and thalassemia, the complete or partial deficiency of HGPRT, superactivity of PRPP synthetase, and hereditary renal hypouricemia. A common denominator in patients with idiopathic and gouty stone formers is a low urinary pH. Uric acid nephrolithiasis is indicated in the presence of a radiolucent stone, a persistent undue urine acidity and uric acid crystals in fresh urine samples. A radiolucent stone in combination with normal or acidic pH should raise the possibility of urate stones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uric acid nephrolithiasis. 778 6

Multiple myeloma (MM) is a clonal plasma cell malignancy that is initiated by a number of mutations and the process of disease progression is characterized by further acquisition of mutations. The identification and functional characterization of these myelomagenic mutations is necessary to better understand the underlying pathogenic mechanisms in this disease. Recent advancements in next-generation sequencing have made the identification of most of these mutations a reality. However, the functional characterization of these mutations has been hampered by the lack of proper and efficient tools to dissect these mutations. Here we explored the possible utility of transcription activator-like effector nuclease (TALEN) genome engineering technology to tailoring the genome of MM cells. To test this possibility, we targeted the HPRT1 gene and found that TALENs are a very robust and efficient genome-editing tool in MM cells. Using cotransfected green fluorescent protein as an enrichment marker, single-cell subclones with desirable TALEN modifications in the HPRT1 gene were obtained in as little as 3-4 weeks of time. We believe that TALENs will greatly facilitate the functional study of somatic mutations in MM as well as other cancers.
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PMID:TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells. 2481 78