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)

A procedure for in vitro sensitization of human lymphocytes against bombesin conjugated to tetanus toxoid (BTT) is described. Bombesin is a tetradecapeptide associated with small cell lung carcinoma. We found that antibody responses against bombesin as well as tetanus toxoid could be generated in vitro by culturing nylon-separated human splenic lymphocytes for 6 days with lipopolysaccharide, phytohemagglutinin-activated lymphocyte supernatants, human AB serum, and bombesin conjugated to tetanus toxoid. Cells sensitized by this procedure were fused to murine myeloma cells, NS-1. The specificities of resulting hybrids were analyzed by enzyme-linked immunoassays and competitive inhibition experiments. Hybrids secreting anti-bombesin (IgM) or anti-tetanus toxoid (IgM or IgG) were obtained. The ratio of IgG to IgM antibodies against tetanus toxoid could be increased by using antigen coupled to Sepharose beads. The sensitization procedure described here offers a system for the study of antigenic stimulation of human B lymphocytes in vitro and for the production of human monoclonal antibodies with the desired specificities.
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PMID:In vitro immunization of human lymphocytes. I. Production of human monoclonal antibodies against bombesin and tetanus toxoid. 384 Aug 24

Mouse hybrid cell clones secreting antigonadotropin releasing hormone monoclonal antibody were developed by fusion of SP2/O-Ag 1.4 myeloma cells with splenocytes of mouse immunized with gonadotropin releasing hormone (GnRH) tagged to tetanus toxoid. The product of hybrid cell clones obtained as ascites fluid from mouse peritoneal cavity had a titre of 10(6) (30-40% binding of 125I-GnRH) in radioimmunoassay. The antibody was IgG2a and Kappa. The association constant (Ka) of the product of hybrid cell clone P(8)16(62) for binding with GnRH was 1.2 X 10(9) L/mole. The monoclonal antibody (P(8)16(62)) was highly specific for the native GnRH and devoid of reactivity with thyroid releasing hormone as tested in competitive radioimmunoassay. The recognition for GnRH agonists by monoclonal was 387-fold less with D-Ser (But)6 des Gly10 GnRH ethylamide and 608-fold less with Bz1-His6 GnRH. Monoclonal anti-GnRH antibody was competent to neutralize the in vivo bioactivity of the hormone as evident by the block of estrus cycle and termination of pregnancy in mice. Termination of pregnancy in animals receiving anti-GnRH monoclonal could be prevented by administration of progesterone.
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PMID:Characteristics and bioefficacy of monoclonal antigonadotropin releasing hormone antibody. 388 52

The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types. Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major gammaG1-type. However, a high preponderance of molecules of the minor gammaG2-subgroup was found for antibodies to dextran, levan, and teichoic acid. These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens. Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others. The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals. Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals. Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios. The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda. The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of gammaG2-heavy chains and kappa light chains. By these criteria as well as others, it closely resembled myeloma proteins.
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PMID:Studies on human antibodies. VI. Selective variations in subgroup composition and genetic markers. 416 68

The ability of human myeloma proteins of different classes and subclasses and of macroglobulins (all aggregated with bis-diazotized benzidine or heat) to aggregate washed human platelets and release [(3)H]-serotonin from the platelets was investigated and compared with the activity of normal IgG and tetanus-antitetanus IgG antigen-antibody complexes. Aggregated IgG1, IgG2, IgG3, IgG4, and normal IgG complexes all aggregated platelets and caused release of serotonin to similar extents. In contrast, IgA1, IgA2, IgD, and IgE myeloma proteins as well as IgM macroglobulins were completely inactive in this respect. Approximately 50% of the actvity remained in aggregated, mildly reduced and alkylated IgG myeloma proteins and their Fc fragments, whereas aggregated F(ab')(2) fragments were completely inactive. Addition of fresh serum inhibited the release of serotonin caused by aggregated IgG1 and IgG3 proteins and normal IgG antigen-antibody complexes by about 50% but had no effect upon the release of serotonin obtained with IgG2 and IgG4 proteins. This inhibition appeared to be mediated by complement. The release of serotonin was not accompanied by liberation of the cytoplasmic enzyme lactic dehydrogenase, indicating that no significant lysis of the platelets occurred. Addition of neutrophils did not enhance the serotonin release.
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PMID:Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses. 470 Apr 96

An Epstein-Barr virus (EBV)-transformed human B cell line (B6) producing anti-tetanus toxoid (TT) antibody was fused with a nonimmunoglobulin (Ig)-producing murine myeloma and selected in hypoxanthine-aminopterin-thymidine (HAT) medium containing 10(-5) M ouabain. Surviving cells were cloned by limiting dilution and confirmed as hybrids by karyotype analysis and G-11 staining. Hybridomas were stable and secreted 10-fold more anti-TT antibody (IgM kappa) than the human parental cell line. In addition, the hybridomas exhibited a markedly reduced growth requirement for serum (1% fetal calf serum). Since EBV can be used to expand rare antigen-specific B cells in the human, the technique described here may be at present the method of choice for producing human monoclonal antibodies.
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PMID:Human anti-tetanus toxoid monoclonal antibody secreted by EBV-transformed human B cells fused with murine myeloma. 609 64

We produced somatic cell hybrids between human myeloma cells and a lymphoblastoid cell line that is hypoxanthine phosphoribosyl transferase-deficient and ouabain-resistant. These hybrids were phenotypically similar to the human myeloma parental cells and grew as well as the human lymphoblastoid parental cells. After counterselection in 6-thioguanine, mutants that were 6-thioguanine-and ouabain-resistant were obtained, one of which was used as a fusion partner with lymphoblastoid B cells that produce anti-tetanus toxoid (TT) antibodies. These hybrids secreted human anti-TT monoclonal antibodies in much larger amounts than the parental lymphoblastoid cells, and were stable for a period of over 10 mo until the present time. Thus, by hybridizing plasmacytomas with lymphoblastoid cells, we constructed a fusion partner that secretes large amounts of immunoglobulin (Ig), grows at a fast rate, has a high fusion frequency, and supports the production of monoclonal antibodies over long periods of time. Moreover, anti-TT antibody-producing hybrids have been grown as solid tumors in irradiated BALB/c nude mice and then adopted to ascites growth, producing 1 to 8 mg of human immunoglobulin per 1 ml of ascites fluid.
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PMID:A human hybrid myeloma for production of human monoclonal antibodies. 609 64

A monoclonal antibody designated M2 arose from the fusion of mouse myeloma cells with splenocytes from a rat immunized with particulate fraction from early postnatal mouse cerebellum. Expression of M2 antigen was examined by indirect immunofluorescence on frozen sections of developing and adult mouse cerebellum and on monolayer cultures of early postnatal mouse cerebellar cells. In adult cerebellum, M2 staining outlines the cell bodies of granule and Purkinje cells. A weaker, more diffuse staining is seen in the molecular layer and white matter. In sections of newborn cerebellum, M2 antigen is weakly detectable surrounding cells of the external granular layer and Purkinje cells. The expression of M2 antigen increases during development in both cell types, reaching adult levels by postnatal day 14. At all stages of postnatal cerebellar development, granule cells that have completed migration to the internal granule layer are more heavily stained by M2 antibodies than are those before and in process of migration. In monolayer cultures, M2 antigen is detected on the cell surface of all GFA protein-positive astrocytes and on more immature oligodendrocytes that express 04 antigen but not 01 antigen. After 3 days in culture, tetanus toxin positive neurons begin to express M2 antigen. The same delayed expression of M2 antigen on neurons is observed in cultures derived from mice ranging in age from postnatal day 0 to 10.
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PMID:Monoclonal antibody (M2) to glial and neuronal cell surfaces. 617 Jul 57

Monoclonal antibodies against tetanus toxin were produced to obtain highly specific antisera. Ten hybridoma cell lines producing monoclonal antibodies were derived from the fusion of rat myeloma cells and spleen cells from rats immunized with tetanus toxoid. Eight produced monoclonal antibodies specific for determinants on toxin and toxoid, whereas two were specific only for determinants on the toxoid. The antibodies produced by hybridomas were characterized by determination of the class of light and heavy chain components, epitope specificity, toxin neutralization, and subunit specificity. All of the antibodies contained kappa light chain, eight contained the gamma 1 heavy chain, and the remaining two contained the gamma 2a heavy chain. Five distinct epitopes were indicated by competition assay of paired monoclonal antibodies, and 4 of the 10 monoclonal antibodies neutralized the in vivo activity of tetanus toxin. The four neutralizing monoclonal antibodies and one other were specific for the C fragment of the heavy chain of the toxin molecule.
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PMID:Production and characterization of monoclonal antibodies to tetanus toxin. 619 85

This work makes a critical evaluation of EBV transformation as a tool for establishing human antibody producing lines. Since Steinitz et al. described the technique in 1977, at least 9 lymphoid cell lines with predetermined specificities have been reported with activity against NNP, TNP, A-CHO, phosphorylcholine, human Ig, Rh-D antigen and tetanus toxoid. Most successful attempts were based on the choice of immune donors and on the adequate selection of peripheral antigen-specific B cells with antigen-coated erythrocytes. When lines were established, a further selection of antigen-specific lymphoblastoid cells using several steps of rosetting or cloning proved to be necessary, in order to get mono- or oligoclonal lines, and thus to maintain an antibody production for a prolonged period (up to 18 months). Secretion ranged from 0.1 to 16 micrograms antibody per ml, depending on the lines. Two of the antibodies produced are used as biological reagents. When compared to hybridomas, EBV transformed lines have the disadvantage of a lower colony forming efficiency, and usually a lower level of antibody secretion. On the other hand, if fusion of EBV induced lymphoblastoid cell lines proves to be possible with human myeloma lines and results in the creation of hybridomas, EBV transformation might reveal a useful technique to raise minute amounts of antigen specific cells to the amount of cells required for the fusion techniques.
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PMID:Induction of antibody-producing cell lines by Epstein-Barr virus. 628 60

A monoclonal antibody, termed anti-NSP-5 (anti-Neural cell Surface Protein-5) was obtained from an hybridoma generated by fusing rat myeloma cells with splenocytes of a rat immunized with membranes from the cerebella of weaver mutant mice. This antibody reacted with the surface membrane of a subset of neurones in cultures from cerebella and dorsal root ganglia. In both culture systems, only tetanus toxin-positive cells were stained by the antibody. In sections of adult cerebellum a punctate pattern of staining was seen in the molecular layer, the Purkinje cell layer and the upper part of the granule cell layer. The white matter was strongly positive whereas granule cell and Purkinje cell bodies were clearly negative. In sections from adult dorsal root ganglia anti-NSP-5 labeled most sensory neurones including their axones in the dorsal roots. The expression of the antigen was developmentally regulated. It could not be detected in cerebellar cultures prepared from animals younger than 7 days, in good agreement with the data obtained on tissue sections. Similarly, the antigen could not be detected by immunoblotting in neonatal spinal cord, but a NSP-5-reactive band was present at postnatal day 7. The antibody bound a polypeptide of around MW 180 000 in extracts prepared from adult mouse spinal cord or cerebellum. When purified by immunoaffinity chromatography the antigen co-eluted with numerous strongly associated polypeptides. Upon subcellular fractionation most of it remained associated with a Triton-X100 insoluble fraction thus co-distributing with the cytoskeleton.
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PMID:Identification and immunolocalization by monoclonal antibody of NSP-5, a surface polypeptide of neural cells. 638 64


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