PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Chorionic Gonadotropin, beta Subunit, Human”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). I. Alternative macromolecular carriers.

The antibody response obtained after vaccinating rabbits with the beta-subunit of human chorionic gonadotropin (beta-hCG) linked to several protein and polysaccharide carriers was measured. In all but one preparation, carbodiimide was used to couple the beta-hCG to the carrier. Tetanus toxoid (TT) and cholera vaccine proved the most effective carriers among those examined. TT from different manufacturers proved to be greatly different in free amino group content and differed in ability to participate in the coupling reaction. Reasonably good replication of the coupling reaction was obtained with different production lots from the same manufacturer. Inferior antigenic response was obtained with the products of coupling beta-hCG to H. pertussis, influenza vaccine, polylysine, pneumococcus polysaccharide, or E. coli polysaccharide. The findings indicate TT and cholera vaccine to be especially effective in enhancing the antigenicity of a weakly antigenic peptide but point to significant differences in the TT from different manufacturers.

Adjuvants, Immunologic↗
PubMed1993

Immunohistochemistry of molar and non-molar placentas with special reference to their differential diagnosis.

An immunohistochemical study analyzing distributions of beta-subunit human chorionic gonadotropin (beta HCG), human placental lactogen (HPL), placental alkaline phosphatase (PLAP), and monoclonal anti-cytokeratin (PKK1) was undertaken to determine whether the reactivity of these antigens might assist in the differential diagnosis of molar and non-molar hydropic placentas. A total of 16 complete hydatidiform moles, 15 partial hydatidiform moles, 12 hydropic abortuses and 39 non-hydropic placentas with gestational age ranging from 4 to 40 weeks was examined. In both the complete and partial moles, many syncytiotrophoblasts stained for beta HCG, HPL, PLAP and PKK1 although the staining intensity of beta HCG in the partial moles was weak compared with the complete moles. The staining patterns in the hydropic abortuses were almost the same as those in the normal first trimester placentas and had no distinct features from the partial moles. Trophoblastic hyperplasia is an essential feature in differentiating partial moles from hydropic abortuses. With regard to the immunostaining patterns of these antibodies, there was no significant difference to enable delineation between partial and complete moles, or between a hydropic abortus and a partial mole. Monoclonal anti-cytokeratin was most sensitive for trophoblasts, but less specific for intermediate trophoblasts than HPL. Although an immunohistochemical study using antibodies against beta HCG, HPL, PLAP and PKK1 is very useful for characterizing various trophoblasts, it is considered that an immunohistochemical study may not be a suitable tool for the differential diagnosis of molar and non-molar hydropic placentas.

Adolescent↗
PubMed1973

Ectopic production of the isolated beta subunit of human chorionic gonadotropin.

A material similar to the beta subunit of human chorionic gonadotropin (hCG-beta) was detected in serum (300 ng/ml) and tumor extract from a 75-yr-old man with pancreatic adenosquamous carcinoma. This material was indistinguishable from hCG-beta in three different types of radioimmunoassay that displayed widely varying reactions with glycoprotein trophic hormones and their subunits. In gel chromatography there appeared to be heterogeneity of the serum beta-like immunoactivity, including one component that coeluted with standard hCG-beta tracer and another immunologically indistinguishable component that displayed a slightly lower elution volume. Neither complete human chorionic gonadotropin (hCG) nor its alpha subunit was detected in radioimmunoassays of serum, before or after fractionation, or in tumor extract. The absence of complete hCG was confirmed in a gonadotropin bioassay sensitive to 15 ng of hCG, which showed no bioactivity in serum or tumor extract containing 450 and 90 ng of hCG-beta, respectively. This case probably represents the first demonstration of isolated polypeptide subunit production of ectopic origin and suggests that hCG-beta, as well as other subunits, may prove useful as cancer markers.

Adenocarcinoma↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). II. Use of compounds of the muramyl dipeptide (MDP) family as adjuvants.

Earlier tests of an antipregnancy vaccine consisting of the beta-subunit of human chorionic gonadotropin (beta-hCG) linked by reaction with a carbodiimide reagent to tetanus toxoid (TT) and adsorbed on Al(OH)3 resulted in antibody responses that were judged inadequate in some women. Experiments were therefore conducted to evaluate the effectiveness of additional adjuvants in increasing the antibody response. Muramyl dipeptide (MDP) and several of its analogs were formulated with the vaccine and tested in rabbits. Some of the analogs, and notably N-acetyl-normuramyl-L-alanyl-D-isoglutamine, elicited substantial increments in the ability of the antisera to bind [125I]hCG and in its ability to neutralize hCG in the rat uterine weight assay. The effectiveness of these peptides was greatest when formulated in a water-in-oil emulsion. Increments of 10 fold were attained using a vegetable oil as the oil component. The MDP analogs were much less effective as adjuvants when formulated in oil-in-water emulsions or in aqueous suspensions of the antigen. It is concluded that selected MDP analogs incorporated in a water-in-vegetable oil emulsion can markedly increase the circulating antibody response to the beta-hCG-TT vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2004

Identification of cross-reactive and restricted epitopes localized on human chorionic gonadotropin beta-subunit by monoclonal antibodies.

Human chorionic gonadotropin (hCG) belongs to the family of glycoprotein hormones. All members of the family are composed of an identical alpha subunit and structurally related beta subunit which confers biological specificity. Specific quantification and functional analysis of hCG require the use of monoclonal antibodies recognizing different epitopes of hCGbeta. This study describes the production and characterization of monoclonal antibodies (MAbs) to hCGbeta with no cross-reactivity to other glycoprotein hormones. Spleen cells from Balb/c mice immunized with hCG were fused with mouse SP2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine, and thymidine (HAT) selective medium and cloned by limiting dilution assay. Antibody-secreting cells were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of secreted MAbs was further analyzed, using a panel of highly purified and recombinant glycoprotein hormones, their subunits and peptides representing the C-terminal end of hCGbeta (hCGbeta-CTP) by ELISA and immunoblotting. The affinity constant (K(aff)) was also determined by ELISA. Three murine hybridomas designated G5M1, B12M2 and F4M3 were obtained that secrete MAbs specific for hCGbeta. The G5M1 MAb reacts only with hCGbeta, hCGbeta-CTP and intact hCG with no detectable cross-reaction with hCGalpha or any of the other glycoprotein hormones. The specificity of B12M2 MAb is very similar to G5M1, but it does not react with hCGbeta-CTP. The F4M3 MAb also has similar specificity to G5M1 and B12M2, but it strongly cross-reacts with hLH. The affinity constant (Kaff) of G5M1, B12M2 and F4M3 was found to be 4.28 x 10(9), 5.2 x 10(8), and 1.97 x 10(9) M(-1), respectively. Our results indicate that G5M1 and B12M2 MAbs are specific for hCG and recognize epitopes restricted to hCGbeta, but F4M3 recognizes a common epitope expressed both on hCGbeta and hLHbeta.

Animals↗
PubMed2006

Expression of human chorionic gonadotropin beta-subunit type I genes predicts adverse outcome in renal cell carcinoma.

Expression of the free beta-subunit of human chorionic gonadotropin (hCGbeta) in malignant tumors is frequently associated with aggressive disease. The pretreatment serum concentration of hCGbeta is an independent prognostic variable in renal cell carcinoma (RCC). The three so-called type II genes (hCGbeta 3/9, 5, and 8) have been shown to be up-regulated in relation to type I genes (hCGbeta 6/7) in some malignant tumors. We developed a reverse transcription-polymerase chain reaction method for quantification of relative levels of the mRNAs for the two types of hCGbeta genes and studied the association between the expression in RCC tissue (n = 104) and clinical outcome. hCGbeta mRNA expression was detected in 40% (42 of 104) of the tumors, and in 40 of these (93%), this consisted of hCGbeta type I mRNA only, whereas type II hCGbeta mRNA was detected in two samples. hCGbeta mRNA expression was significantly associated with a shorter disease-specific (log-rank P = 0.023; median survival 1.4 versus 7.9 years) and overall survival (log-rank P = 0.011). In a Cox regression model, stage (P < 0.0001) and hCGbeta mRNA expression (P < 0.0001) were independent prognostic variables. We conclude that expression of type I hCGbeta genes indicates adverse prognosis in RCC.

Adult↗
PubMed1986

A distinctive form of human chorionic gonadotropin beta-subunit-like material produced by cervical carcinoma cells.

The DoT and CaSki human cervical carcinoma cell lines ectopically produce material immunologically similar to the beta-subunit of human chorionic gonadotropin (hCG beta). Culture fluids were analyzed by gel filtration chromatography and radioimmunoassay (RIA) using (a) antiserum directed to conformation-specific (core-directed) determinants not involving the carboxyl-terminal peptide (CTP) in hCG beta purified from urinary hCG (i.e., standard hCG beta) or (b) antiserum directed to the CTP in standard hCG beta. CTP-directed RIA recognized a peak of hCG beta-like immunoreactive material that eluted in the same position as standard hCG beta. However, core-directed RIA recognized additional hCG beta-like material (i.e., ectopic beta-II), most of which eluted before standard hCG beta. CaSki cells were incubated with [3H]mannose, [3H]proline, and [3H] leucine, and the spent medium was immunoprecipitated and analyzed by gel electrophoresis. Several labeled peaks were detected in the lane from the anti-hCG beta X Sepharose immunoprecipitate, one of which corresponded in mobility to standard hCG beta, with two more intense components migrating at higher apparent molecular weights. Carboxypeptidase Y digestion released only 0.2 mol equivalents each of [3H]proline and [3H]leucine from the labeled CaSki material immunoprecipitated with anti-hCG beta X Sepharose, compared to 1 mol equivalent each in similar analysis of standard hCG beta. These findings were consistent with the absence of the 4-carboxy-terminal amino acids from 80% of the hCG beta-like immunoreactive material secreted by CaSki cells. The affinity purified ectopic beta-II failed to combine with standard hCG alpha under conditions in which combination of standard hCG beta with standard hCG alpha was essentially complete. Neither aggregation nor proteolytic degradation was the cause of failure of ectopic beta-II to combine with hCG alpha. We conclude that both the DoT and CaSki cervical carcinoma cell lines secrete a distinctive form of hCG beta-like material, ectopic beta-II. Lack of recognition by CTP-directed antisera and amino acid analysis suggest that ectopic beta-II may lack the CTP, despite its apparent larger size relative to standard hCG beta.

Amino Acids↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). III. Evaluation of various vehicles and adjuvants.

Rabbits were used to test the efficacy of several materials as supplementary adjuvants when administered as part of a vaccine formulation consisting of the beta-subunit of human chorionic gonadotropin linked to tetanus toxoid (beta-hCG-TT) and adsorbed on Al(OH)3. In the amounts used, Corynebacterium parvum, levamisole, thymic factor, and N,N-dioctadecyl-N',N'-bis(2-hydroxyethyl)propanediamine exhibited little adjuvant activity although the latter material elicited marginal increments when incorporated in liposomes. A Salmonella lipopolysaccharide preparation (SPLPS) and a streptococcal preparation (OK-432) each gave approximately 7-fold increments in titer. The SPLPS preparation was pyrogenic at the doses used. OK-432 was nonpyrogenic and did not cause other evident undesirable effects. It may therefore prove to be a useful adjuvant. It gave a nearly flat dose response curve over the range of 0.5 to 4.0 mg per rabbit. Incorporation of beta-hCG-TT on Al(OH)3 in a water-in-oil emulsion caused a moderate increase in titers. Incorporation into liposomes or an oil-in-water emulsion was not effective.

Adjuvants, Immunologic↗
PubMed1981

A procedure using immobilized antibody for the isolation of the beta-subunit of human chorionic gonadotropin from the culture fluid of a beta-subunit-secreting nontrophoblastic cell line.

Antibody produced against the beta-subunit of hCG was linked to Sepharose 4B and used to isolate ectopic hCG beta secreted by DoT cervical cancer cells in culture. beta-Subunit was eluted with 3 M guanidine-hydrochloride, pH 3.0 (three treatments, 15 min each, at 20 C). The eluted hCG beta was desalted with Sephadex G-25 and concentrated by lyophilization. A single batch of antibody-bound Sepharose was used repeatedly to adsorb hCG beta from liter quantities of spent culture fluid containing 10% fetal bovine serum. The material recovered from 15.75 liters of fluid was pooled and treated a second time with immobilized antibody. Using only immobilized antibody, purification of more than 200,000-fold was achieved, with an overall recovery of about 28%.

Antigen-Antibody Reactions↗
PubMed1995

Bacterial expression of human chorionic gonadotropin alpha subunit: studies on refolding, dimer assembly and interaction with two different beta subunits.

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common alpha subunit but differ in their hormone-specific beta subunit. The common alpha subunit contains two asparagine (N)-linked oligosaccharides. To study the function of carbohydrates on in vitro refolding of alpha subunit and dimer assembly, we generated recombinant non-glycosylated hCG alpha subunit (rNGl-hCGalpha) from E. coli. The expression vector was constructed by inserting hCGalpha cDNA coding for the mature form in-frame into a pQE-30 vector, which contains a 6 x His sequence immediately before the 5'-end of hCGalpha cDNA for subsequent purification of rNG-hCGalpha. The rNG-hCGalpha expressed in inclusion bodies was efficiently purified by immobilized metal chelate affinity chromatography on Ni-NTA resin. SDS-PAGE, solid-phase binding assay and immunoblotting demonstrated the expression of rNG-hCG. Its alpha molecular weight on SDS-PAGE was 14.7 kDa under reducing conditions and 15 kDa for a monomer accompanied with some higher molecular weight oligomer under non-reducing conditions. Reconstitution of rNG-hCGalpha with native hCGbeta and oFSHbeta occurred in very low yield under standard conditions. However, the oxidation-reduction system cystamine (1.34 mM) and cysteamine (7.3 mM) facilitated both the refolding of rNG-hCGalpha and reconstitution of rNG-hCGalpha with native hCGbeta to regain partially correct conformation. These were revealed by conformationally sensitive antibody and receptor binding assays. Cystamine and cysteamine were more effective in the recombination of rNG-hCGalpha with oFSHbeta as indicated by a 22-36-fold decrease in the amount required to cause a 50% competitive inhibition in radioreceptor assay. They have no effect on assembly of rNG-hCGalpha with oLHbeta. Our results suggest the carbohydrate moieties confer greater conformational flexibility to the backbone of the beta subunit and the relative rigidity of the beta subunit may serve as a conformational template of the alpha subunit. The present approach has made it possible to prepare the non-glycosylated gonadotropin alpha subunit in adequate amounts for further study on their biological and topographical features in complete absence of carbohydrate.

Amino Acid Sequence↗
PubMed2001

Ovarian malignant mixed mesodermal tumor producing the free form of the beta-subunit of human chorionic gonadotropin.

We report a patient with ovarian malignant mixed mesodermal tumor (MMMT) that produced immunoreactive human chorionic gonadotropin beta-subunit (IR-hCG beta). Qualitative analysis indicated that IR-hCG beta in the patient's serum represented the free form of the beta-subunit of hCG. Immunohistochemical localization of hCG beta in MMMT was observed in the sarcomatous stroma, but not in the adenocarcinoma component. Reverse transcription-polymerase chain reaction (RT-PCR) for hCG subunits revealed that the mRNA transcripts of two of six hCG beta genes (beta-1 and -2) were predominantly expressed in the tumor tissue. The serum level of free hCG beta correlated with disease status and was helpful for monitoring the response to therapy for MMMT in this patient.

Adenocarcinoma↗
PubMed1979

Ability of human chorionic gonadotropin beta-subunit to inhibit the steroidogenic response to lutropin.

Ability of the beta-subunit of human chorionic gonadotropin to inhibit the response to lutropin (luteinizing hormone, LH) was tested in the immature rat ovarian system and pregnant-mare-serum-gonadotropin-primed rat ovarian system with progesterone production being used as the response. Human chorionic gonadotropin beta-subunit was found to inhibit human and ovine lutropin-stimulated progesterone production. At a constant dose of lutropin, inhibition was dependent on the concentration of beta-subunit. When concentration of the beta-subunit was kept constant at 5.0 microgram/ml and the concentration of lutropin was varied, the inhibition was maximum at the saturating concentration of the native hormone. The alpha-subunit of the human chorionic gonadotropin did not inhibit the response to lutropin. The lutropin/beta-subunit ratio required to produce an inhibition of response was much lower than that required to bring about an observable inhibition of binding.

Animals↗
PubMed1998

Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

Adenocarcinoma↗
PubMed1995

Targeting vaccinia virus-expressed secretory beta subunit of human chorionic gonadotropin to the cell surface induces antibodies.

We carried out experiments designed to study the effect of a protein's localization on its immunogenicity. A novel cell-surface protein was generated from a small, glycosylated secretory protein. The DNA sequence encoding the entire precursor of the human chorionic gonadotropin beta (beta hCG) subunit was fused in the correct reading frame to the DNA sequence encoding the transmembrane and cytoplasmic domains of vesicular stomatitis virus glycoprotein. This chimeric gene was introduced into the vaccinia virus genome to generate a recombinant virus. The recombinant virus, when used to infect animal cells, expressed a 135-amino-acid beta hCG subunit anchored in cellular membranes by the 48 carboxy-terminal amino acids of vesicular stomatitis virus glycoprotein. The immunogenicity of this recombinant virus with respect to its ability to generate anti-hCG antibodies was compared with that of a second recombinant vaccinia virus expressing the native secretory form of beta hCG. All animals immunized with the vaccinia virus expressing beta hCG on the cell surface elicited high titers of anti-hCG antibodies. Even after a single immunization with the recombinant vaccinia virus, the anti-hCG antibody titers persisted for a long period of time (more than 6 months). None of the animals immunized with vaccinia virus expressing the native secretory form of beta hCG showed any hCG-specific antibody response.

Animals↗
PubMed1997

Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin beta-subunit by disruption of disulfide bonds.

The human chorionic gonadotropin beta-subunit (hCGbeta) is a glycoprotein in which 12 cysteine residues pair to form six intramolecular disulfide bonds. In order to elucidate the effect of each disulfide bond on glycosylation of the molecule, we analysed structures of asparagine-linked oligosaccharides of various recombinant hCGbeta produced in Chinese hamster ovary (CHO) cells: wild-type hCGbeta (betaWT) and mutants in which any one of the six intramolecular disulfide bonds had been disrupted by site-directed mutagenesis. SDS-PAGE analysis of betaWT and these mutants before and after digestion with endoglycosidase F and H revealed structural changes in the oligosaccharide moieties of some mutants. In addition, structural analysis of oligosaccharides obtained from metabolically labeled betaWT and a mutant showed that the mutant contained additional high mannose type oligosaccharides. These results suggest that elimination of a specific disulfide bond, resulting in a change in the protein conformation, disturbs the normal assembly of the mature complex type oligosaccharides in the hCGbeta molecule.

Acetylglucosamine↗