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)

The glycoprotein hormones CG, LH, FSH, and TSH are composed of two noncovalently linked subunits, alpha and beta. The beta-subunit confers hormone specificity, while the alpha-subunit is homologous within a species. To help in determining the antigenic structure of the common alpha-subunit, six monoclonal antibodies (mAbs) to the free or heterodimeric alpha-subunit of human (h) gonadotropic hormones have been prepared and, along with two previously isolated mAbs, have been characterized for binding specificity to alpha- and beta-subunits and the human glycoprotein hormones, CG, LH, FSH, and TSH. Each mAb was derived from hybidomas of FO myeloma cells fused with spleen cells from mice immunized with free alpha-subunit, hCG or hFSH. mAbs A101, A102, and E512 were specific for the alpha-subunit but showed the highest affinity for the intact hormone; K2.18, K94.6, E501, E502, and E511 were specific for free alpha. All of the antibodies inhibited binding of 125I-hCG to luteal membrane receptor, and 125I-labeled mAbs did not recognize hCG/receptor complex. Characterization by two-site binding assays using alpha, hCG, or hFSH as antigen revealed that all the mAbs bind to unique sites on alpha which may be overlapping, and which are modified in the intact hormone. The antigenic sites for mAbs E502, E511, and K2.18 are at least partially linear because they bind to reduced, carboxymethylated alpha.
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PMID:The antigenic structure of the human glycoprotein hormone alpha-subunit. I. Characterization of anti-alpha monoclonal antibodies. 170 Nov 33

Using beta and alpha subunits of bullfrog follitropin (FSH) III (pI 6.2), which were highly purified by HPLC, we generated three monoclonal antibodies (MCAs) to FSH beta subunit (FSH beta) and six to FSH alpha subunit (FSH alpha). They were produced by hybridomas derived from the myeloma X63.Ag8.653 and spleen lymphocytes from mice immunized with each subunit. Non-competitive binding tests revealed that one of the MCAs against FSH beta (BF3B25) bound strongly to intact FSH and its beta subunit, but not FSH alpha, lutropin (LH), LH alpha, and LH beta. The immunoblotting results also showed a similar immunological specificity for BF3B25. Cross-reactivity of bullfrog FSH against BF3B25 was 19.4%, when compared with FSH beta in the competitive inhibition assay system. On the other hand, noncompetitive binding tests and immunoblotting results showed that one of the MCAs against FSH alpha (BF3A20) bound strongly to intact LH and FSH and their alpha subunits, but not their beta subunits. The inhibition curves obtained using the alpha subunits of LH and FSH were similar. In the sexually mature bullfrog pituitary, immunoreactive FSH cells stained with MCA BF3B25 were distributed throughout the pars distalis, except for the rostral region, and were polygonal in shape, with well-developed cytoplasm. With respect to distribution and histological characteristics, the immunoreactive LH cells were very similar to the immunoreactive FSH cells when consecutive sections were stained with LH beta-specific MCA (BL4B11). However, immunoreactive TSH cells, revealed by anti-human TSH beta serum, formed clusters in the ventrocentral region of the pars distalis. In young adult pituitary, almost all of the gonadotrophs showed the coexistence of FSH and LH, but some gonadotrophs contained only FSH. The number of immunoreactive alpha-subunit cells stained by BF3A20 was always higher than the sum of the numbers of cells stained by the three beta-subunit-specific antibodies.
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PMID:Immunocytochemical localization of the subunits of glycoprotein hormones (LH, FSH, and TSH) in the bullfrog pituitary gland using monoclonal antibodies and polyclonal antiserum. 210 16

Five monoclonal antibodies to human (h) FSH have been prepared, isolated, and characterized. They were produced by hybridomas derived from FO myeloma cells and spleen cells from mice immunized with hFSH or its beta-subunit (hFSH beta). Two of the antibodies (A101 and A102) which recognized the alpha-subunit of hFSH bound much better when alpha was associated with the beta-subunit forming the intact hFSH molecule than when alpha was in free form. These antibodies showed 9-10%, 2-3%, and 1-3% cross-reactions with alpha-subunits in hTSH, hCG, and hLH, respectively. Two antibodies (B201 and B202) recognized only free beta-subunit. One antibody (B305) recognized free beta-subunit and native hFSH. There was no significant cross-reaction of these antibodies to FSH beta with hTSH, hLH, and hCG. Using solid phase competitive binding and sandwich assays, we compared the epitopes for these antibodies. Antibodies A101 and A102 recognize the same epitope on hFSH alpha. Antibodies B201 and B202 recognize different epitopes, but they seemed to be adjacent. Antibody B305 bound a different epitope than B201 and B202. Such characteristics of these antibodies can be useful for sensitive and specific assay of hFSH or hFSH beta and also may be helpful in studying FSH interaction with its receptor.
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PMID:Monoclonal antibodies against human follicle-stimulating hormone. 241 47

Human chorionic gonadotropin (HCG) is a 40,000 dalton glycoprotein composed of two non-identical alpha- and beta-subunits. HCG and other related pituitary hormones, such as human luteinizing hormones (HLH), human follicle stimulating hormone (HFSH), and human thyroid stimulating hormone (HTSH), consist of nearly identical alpha-chains. However, their beta-chains show a variable degree of amino acid sequence homology. Detection and subsequent quantitative determination of HCG in human biological fluids is useful in early diagnosis of pregnancy and in monitoring of tumor patients. For these applications monoclonal antibodies (McAbs) with defined specificity are required. Several hybridomas secreting McAbs to HCG have been isolated. The hybridoma cells have been developed by fusion of NS1 myeloma cells with spleen cells of Balb/C mice immunized with HCG. With the aid of an enzyme linked immunosorbent assay, six McAbs were characterized. McAbs A-73, A-76 and A-112 recognize an epitope present on the alpha-HCG subunit. McAbs B-68, B-69 and B-106 recognize an antigenic determinant associated with the beta-HCG subunit. Two of these McAbs: B-68 and B-69 are directed against an epitope on the B subunit specific to the HCG molecule and B-106 McAb towards an epitope common to HCG, TSH, LH and FSH molecule. In a hemagglutination test, only the A-73 McAb is capable of inducing agglutination of sheep red blood cells coated with HCG, thus suggesting that this McAb recognizes a repeating epitope on the alpha-HCG molecule.
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PMID:Development of monoclonal antibodies directed against different epitopes of human chorionic gonadotropin. 243 77

We generated a high-affinity and highly specific monoclonal antibody (BL4B11)-producing hybridoma against bullfrog lutropin (LH) beta by fusing mouse myeloma, X63.Ag8.653, with spleen lymphocytes obtained from BALB/c mice immunized with bullfrog LH-IV (pI 9.3) beta-subunit. The resultant antibody-secreting hybridoma was injected into intraperitoneally pristane-primed BALB/c mice to obtain a large amount of antibody. Noncompetitive binding tests revealed that the ascitic fluid (BL4B11) could be diluted up to 1:12,000 for 50% binding to 125I-labeled bullfrog LH beta and also bound strongly to bullfrog intact LH, but not to LH alpha, follitropin (FSH), FSH alpha, FSH beta, and rat glycoprotein hormones (LH, FSH, and thyrotropin (TSH) significantly. The immunoblotting results also showed a similar immunological specificity of BL4B11. Cross-reactivities of bullfrog LH, FSH beta, FSH, LH alpha, and FSH alpha against BL4B11 were 9.69, 3.76, 2.40, 1, and 1%, respectively, when compared with bullfrog LH beta in the competitive inhibition assay system. The affinity constant (Ka) of the BL4B11 was 1.09 X 10(9) M-1. In the sexually mature bullfrog pituitary, immunoreactive LH cells which were revealed by this BL4B11 were distributed throughout the pars distalis except the rostral region. They were especially large, numerous, and polygonal, with well-developed cytoplasm. In the rostral region, immunoreactive LH cells were larger and more intense than those in the central region. In the case of young bullfrog, several immunoreactive LH cells were found only in the dorsocaudal region of the pars distalis. The distribution and histological characteristics of immunoreactive LH cells were different from those of immunoreactive TSH cells revealed by anti-human TSH beta serum.
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PMID:Production and characterization of a monoclonal antibody against the beta-subunit of bullfrog lutropin. 349 61

The hormonal mechanisms involved in the development of gynaecomastia accompanying the treatment of multiple myeloma in adult men have been investigated by studying levels of circulating testosterone (T), oestrone (EI), oestradiol (E2), sex-hormone binding globulin (SHBG), prolactin (PRL) and the gonadotrophins LH and FSH, before, during and after development of gynaecomastia in 4 men. These have been compared with 5 closely matched men who did not develop gynaecomastia during similar treatment for myeloma. Levels of circulating T fell, and levels of E1 and E2 rose during treatment periods in all subjects, and the changes were statistically significant in subjects developing gynaecomastia, which resolved as levels of sex steroid returned towards normal following cessation of treatment. We conclude that treatment of adult men for myeloma results in testicular dysfunction with a reduction in circulating T and a rise in circulating oestrogens. These changes are most marked in subjects developing gynaecomastia in whom the normal breast tissue is stimulated by a subtle, transient oestrogen:androgen imbalance in favour of oestrogens.
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PMID:Gynaecomastia complicating the treatment of myeloma. 640 38

Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG1 subclass. Affinities of antibodies for TSH were in the range 2 x 10(8)-5 x 10(10) M-1. Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (alpha) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays.
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PMID:Characterization of monoclonal antibodies directed against human thyroid stimulating hormone. 710 29

Monoclonal antibodies (Mabs) against human chorionic gonadotropin hormone (hCG) were raised by hybridoma technology using Sp2/0 myeloma cells as fusion partner. Sixty-five percent of the total culture wells exhibited hybrid growth and 8% of the total wells (13 culture wells) contained anti-hCG secreting hybrids. A positive hybrid cell line secreting antibodies against the free alpha-subunit of hCG was cloned twice by limiting dilution method and eighty four clones were obtained that secreted monoclonal antibodies anti-alpha hCG. One of these hybridoma clones (1C4) secreting monoclonal antibodies against the free alpha-subunit of hCG was selected for purification and characterization purposes. This hybridoma cell line secreted monoclonal antibodies of IgG1 subclass, which were purified by affinity chromatography on Protein A Sepharose CL-4B column with a final relative recovery of antibody activity of 75% and a purification factor of about 12. The purified preparation was analyzed by SDS-PAGE, native PAGE, and IEF. Specificity studies of this Mab revealed that it recognized specifically an epitope on the free alpha-subunits of hCG, FSH, LH, and TSH as determined by enzyme immunoassays. On the other hand, this Mab exhibited crossreactivity with other pituitary hormones either as free subunits or intact molecules as follows: alpha hCG 100%; intact hCG 1.8%; beta hCG 0.14%; alpha FSH 24.5%; intact FSH 0.8%; beta FSH 0.09%; alpha LH 20.5%; intact LH 0.9%; beta LH 0.08%; alpha TSH 50.5%; intact TSH 3.7%; beta TSH 0.07%; The affinity constant (K) of this Mab with respect to free alpha-subunit of hCG was found to be 1.5 x 10(7) I/mol as determined by the simple antibody dilution analysis method.
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PMID:Purification and characterization of monoclonal antibodies against the free alpha-subunit of human chorionic gonadotrophin. 1139 60

POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.
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PMID:An Adult with Polyneuropathy and Hypogonadism due to Poems Syndrome. 2905 30