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 65-kDa estrogen receptor (ER) protein has been demonstrated both by sucrose gradient analysis and by immunoblot, using anti-ER monoclonal antibodies (MAbs). Since the ER is denatured in many experimental situations, such as formaldehyde fixing of samples for histochemistry and electroimmunoblotting studies, in this work we used a denatured 60-70-kDa ER-rich protein preparation as antigen for mice immunization in order to raise anti-ER MAbs. That material was obtained by affinity purification on an allyl-estradiol matrix of the MCF-7 cytosolic ER, followed by further isolation and enrichment by PAGE. NS-1 myeloma cells and spleen lymphocytes from the immunized mice were fused, and resultant hybridoma colonies were screened by [125I]-estradiol-labelled nuclear ER immunoprecipitation. The isolated MAb, E476, shows a moderate ability to precipitate ER and reacts strongly with a 46-kDa antigen in Western blot assay. The 46-kDa antigen was not detectable in native cytosol but became reactive after 50% ammonium sulfate precipitation of cytosolic proteins. The 46-kDa antigen appeared concentrated in the NaSCN plus estradiol eluate of the affinity column used for cytosolic ER purification. Freshly prepared 60-70-kDa material from the preparative gel electrophoresis did not show any E476 reactivity. However, when the 60-70-kDa proteins were frozen, thawed and speed vacuum concentrated, the 46-kDa antigen became detectable. Storage increased the reactivity of the 60-70-kDa material with the E476 MAb. The 46-kDa antigen was present only in the ER positive cell lines, and was absent in all negative cell lines tested. The 46-kDa protein is also present in the ER positive human breast cancer specimens. We conclude that the 46-kDa protein identified with the E476 MAb in human breast cancer is probably a naturally occurring ER fragment.
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PMID:A 46-kDa antigen associated with estrogen receptor in human breast cancer. 338 60

We have recently demonstrated that one of our monoclonal antibodies (MAB's) to glial fibrillary acidic protein (GFAP) recognizes an epitope on this molecule which is to a large degree blocked during fixation with formaldehyde or crosslinking with Dithiobis (Succinimidyl) Propionate (DTSP). This was shown to be due to the crossbinding of a single or a number of proteins to the GFAP and is not due to a change in the epitope on GFAP induced by the fixation itself. In an attempt to produce further MAB's capable of recognizing epitopes on the GFAP molecule available following formaldehyde fixation, we immunized BALB-C mice with cytoskeletal preparations of human glioma cells which contain GFAP where the blocking protein or proteins were crossbound by DTSP or formaldehyde to the GFAP. Following fusion of the spleen lymphocytes to Sp 2/0 myeloma cells we have cloned hybridomas which produce antibodies that recognize GFAP in formaldehyde fixed tissues. This method presents the antigen in its native "fixed" state for the mouse's immune system and avoids the production of MAB's which (although excellent for immunochemical studies) do not recognize any epitopes available on the molecule in question in formaldehyde fixed tissues. Antibodies so produced are of great interest in routine pathology where most tissues are still, unfortunately, undiscriminately fixed in formalin. The results also show that GFAP varies immunologically in different species (i.e. human v. rat/mouse) and confirm that the GFAP of the PNS is immunologically distinct and/or associated with different proteins from that found in the CNS.
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PMID:Monoclonal antibodies to GFAP epitopes available in formaldehyde fixed tissue. 354 74

Monoclonal antibodies (mabs) have been raised against human transthyretin (hTTR). The protein was isolated by an affinity chromatography procedure using Sepharose-hRBP and BALB/c mice were immunized. Following fusion with SP 2/0 myeloma cells, 26 single cell clones producing antibodies against hTTR were isolated. These mabs have been characterized and efforts have been made to establish the epitopes that they recognize. So far at least two different epitopes have been identified both residing in a mid-region fragment corresponding to the amino acid sequence 35-103 of the hTTR subunit. All mabs have been found suitable for immunohistochemical localization of hTTR even in formaldehyde fixed and paraffin embedded tissues.
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PMID:Monoclonal antibodies to transthyretin. 379 88

A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. No rise in death rates was observed for asthma, bronchitis or emphysema, in spite of other evidence of a high risk of occupational asthma, due to exposure to piperazine. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time of at least 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time of at least 15 years was used. A case-referent study within the cohort did not reveal any significant association between any specific chemical exposure and cancer morbidity.
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PMID:Mortality and cancer morbidity among workers in a chemical factory. 382 3

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

Fusion of splenic lymphocytes from Lewis rats, immunized with affinity-purified estrogen receptor from the cytosol of MCF-7 human breast cancer cells, with two different mouse myeloma lines, has provided 13 monoclonal hybridoma lines secreting antiestrophilin antibodies, each of which (with one possible exception) recognizes a different antigenic determinant in the human receptor molecule. Of this library of monoclonal antibodies, some react with estrophilin from all sources tested, some react with mammalian but not avian receptors, whereas one preparation appears specific for estrophilin from primate sources. By proteolytic digestion under controlled conditions with mercury-deactivated papain, chymotrypsin, and trypsin, respectively, it is possible to remove sequentially the determinants recognized by one, two or three of the monoclonal antibodies, leaving the epitopes for the six remaining antibodies investigated on the steroid-binding portion of the receptor. The proteolytic fragment containing the epitope most readily removed (by mercuripapain) also contains the DNA-binding domain of the activated receptor molecule. Immunocytochemical staining, using the peroxidase procedure with various monoclonal antibody preparations, of frozen sections of human breast cancer tissue, fixed in ethanol or in picric acid-formaldehyde reagent, shows clearly that the majority of the native receptor, which appears in the cytosol after tissue homogenization, is actually localized within the nuclear compartment in the intact cell. The immunocytochemical technique also permits the identification of mixed populations of receptor-containing and non-containing cells in human breast cancers.
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PMID:Immunochemical studies of estrogen receptors. 620 Jul

Cryostat sections of human central nervous system (CNS) tissue absorbed sheep erythrocytes (E) sensitized with rabbit IgG antibody (A). The indicator cells bound to the choroid plexus, to the leptomeninges covering the brain and spinal cord, to the arachnoid granulations and to the perivascular tissue of the neural parenchyma. Unsensitized E or E sensitized with F(ab')2 fragments of IgG were not bound. The reactions were inhibited by pooled human IgG, human IgG1 and IgG3 myeloma proteins, and Fc fragments of pooled human IgG. Whole human IgG2 myeloma protein, IgM, IgA, F(ab')2 fragments of pooled human IgG and albumin did not inhibit. Experiments with reduced and alkylated IgG, EDTA, iodoacetamide, 2-mercaptoethanol, various pHs and salt concentrations, formaldehyde, periodic acid and neuraminidase did not reveal any differences between the Fc gamma receptors in the separate anatomical areas. The Fc gamma receptors in human CNS are thus apparently very similar.
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PMID:Properties of Fc gamma receptors in the human central nervous system. 628

To develop monoclonal reagents for antigenic analysis and serotyping of Campylobacter spp., hybridoma cell lines were produced by fusion of mouse myeloma cells and spleen cells from mice immunized with Formalin-treated Campylobacter jejuni organisms. An enzyme immunoassay was used for preliminary screening of the cell culture supernatants and ascites. Twenty-nine clones which reacted with the immunogen were obtained. Seven of these clones were positive in passive hemagglutination tests with sheep erythrocytes coated with boiled saline extract of whole bacteria; four of these reacted with the purified polysaccharide preparation and with the autoclaved saline extract, but not with lipopolysaccharide prepared from the immunogen strain. Two of the antipolysaccharide clones agglutinated live bacteria in slide tests. Four additional clones gave positive slide agglutination tests with live bacteria, but in tube testing no clones agglutinated Formalin-treated bacteria. No cross-reactions with unrelated bacteria were seen, but several clones reacted in the enzyme immunoassay with many of the 24 Campylobacter strains studied. The clone which gave the highest mean enzyme immunoassay values with Campylobacter coli and C. jejuni strains also reacted with Campylobacter fetus subsp. veneralis and C. fetus subsp. fetus strains. This clone also gave the highest enzyme immunoassay value with an acid glycine extract of the immunogen, which indicates the presence of common antigens in the extract. The results suggest that monoclonal antibodies may be used to devise serotyping schemes for Campylobacter spp.
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PMID:Analysis of Campylobacter jejuni antigens with monoclonal antibodies. 636 54

Monoclonal antibodies were prepared by the fusion of murine myeloma NS1 cells with spleen cells of BALB/c mice immunized with Formalin-killed elementary bodies of the Chlamydia trachomatis L2 serovar. The specificity of these monoclonal antibodies was determined with a solid-phase immunoassay in which HeLa 229 cells infected with C. trachomatis serovars D, G, H, I, L2 and the Chlamydia psittaci meningopneumonitis strain Cal-10 were used. An immunoglobulin G3 monoclonal antibody (L2I-6) was identified that reacted with both C. trachomatis- and C. psittaci-infected HeLa cells. The immunoreactivity of the genus-specific epitope was heat resistant (100 degrees C, 10 min) but was destroyed by sodium metaperiodate treatment. Further characterization of the chlamydial specificity of monoclonal antibody L2I-6 by microimmunofluorescence showed that it was reactive with all 15 C. trachomatis serovars and seven C. psittaci strains isolated from five different animal species. We undertook studies to identify the biochemical nature of the chlamydial component on which the genus-specific epitope was located. The immunoreactive component was isolated by hot phenol-water extraction of dithiothreitol-reduced chlamydial elementary bodies. The component was positive in the Limulus amoebocyte lysate test (results of Limulus amoebocyte lysate assay were identical with those of Salmonella typhimurium LT2 SAI 377 Re lipopolysaccharide [LPS]), contained 8.8% 2-keto-3-deoxyoctulosonic acid, was resistant to proteinase K, and possessed electrophoretic mobility and silver-staining characteristics in sodium dodecyl sulfate-polyacrylamide gel electrophoresis consistent with a rough LPS or glycolipid. On the basis of these findings, we conclude that the genus-specific epitope recognized by monoclonal L2I-6 is located on chlamydial LPS. We further characterized the antigenic properties of the chlamydial LPS epitope by examining the immunoreactivity of monoclonal antibody L2I-6 by immunoblotting analyses against isolated LPSs extracted from Neisseria gonorrhoeae, S. typhimurium, and Escherichia coli. Monoclonal antibody L2I-6 did not bind LPS of these organisms, demonstrating that the chlamydial genus-specific LPS epitope is apparently not shared by these gram-negative bacteria. We were able, however, to show that the chlamydial LPS does share antigenic determinants with LPS of gram-negative organisms. Polyclonal rabbit antisera raised against S. typhimurium Re LPS or lipid A showed intense immunological cross-reactivity with chlamydial LPS by immunoblotting.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal antibody against a genus-specific antigen of Chlamydia species: location of the epitope on chlamydial lipopolysaccharide. 642 19

The surface anionic site distribution on membranes of a monoclonal antibody-producing hybridoma cell line, and its two parental cells: normal spleen cells of immunized BALB/c mice and cells from a mouse myeloma line (NS-1), were investigated with the aid of the cationized ferritin (CF) labelling method, following glutaraldehyde/formaldehyde fixation of cells. The patch-like CF distribution on the hybridoma cells is similar to that of the NS-1 myeloma cells, but distinct from the even and continuous CF distribution of the immunized and nonimmunized normal spleen lymphocytes. The similarity in the formation of patch-like CF heaps, both on myeloma and hybrid cells is discussed in respect to the surface charge characteristic determined by cell fusion.
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PMID:Distribution of surface anionic sites on mouse hybrid myelomas. 662 23


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