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PubMed2002

Complication of cesarean section: pregnancy on the cicatrix of a previous cesarean section.

OBJECTIVE: To probe into the clinical manifestation, diagnosis, as well as treatment of pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester. METHODS: Analysis of 14 patients with pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester was made after conservative treatment by drugs from January 1996 to December 1999. RESULTS: The 14 patients with a pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester were painless, had slight vaginal bleeding, and concurrently had increased serum beta-subunit human chorionic gonadotropin (beta-HCG). Doppler ultrasonic examination revealed an obvious enlargement of the previous cesarean section cicatrix in the uterine isthmus, and found a gestational sac or mixed mass attached to the cicatrice, with a very thin myometrium between the gestational sac and bladder walls. Among the 14 patients, 12 patients had crystalline trichosanthes injected into the cervix, mifepristone taken orally, or methotrexate in the form of intramuscular injection. Following this procedure, their serum beta-HCG dropped to normal. The other 2 patients had a total hysterectomy. CONCLUSIONS: Pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester is a complication of cesarean section. Early diagnosis and effective conservative treatment by drugs are instrumental in decreasing the potential occurrence of uterine rupture, which is also conducive to preserving the patient's future fertility.

Adult↗
PubMed2006

[OSCAR (one-stop clinic for assessment of fetal risk): our experience with first trimester screening for chromosomal abnormalities].

OBJECTIVES: In recent years has been intensified an effort to develop early more exact non-invasive methods for prenatal diagnosis. We report our experience to screen trisomy 21 and other chromosomal abnormalities in the first trimester in so-called OSCAR (One-Stop Clinic for Assessment of Fetal Risk). DESIGN AND SETTING: It is a retrospective study held at the Department of Medical Genetic and Fetal Medicine, Teaching Hospital, Olomouc. METHODS: A group of 2110 pregnant women has been screened by maternal age as a background risk, fetal nuchal translucency, nasal bone as ultrasound markers as well as maternal serum level of free beta-subunit human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) as a biochemical markers between 11 - 13+6 weeks of pregnancy from January 2004 to December 2005. The Fetal Medicine Foundation Guidelines and software were the methods and tools used for screening. Karyotyping by chorionic villous sampling or amniocentesis was offered to women with risks > or = 1 in 300. RESULTS: We reported 100% sensitivity for this method for a 4, 6% false positive. There was detected 21 chromosomal abnormalities in which 10 were trisomy 21. This is the first result to be published for this screening method in the Czech Republic. CONCLUSION: In our experience first trimester screening for trisomy 21 and other aneuploidies has a high sensitivity with a low false positive rate and can be delivered in an efficient manner in a one-stop multidisciplinary clinic.

Adolescent↗
PubMed2002

Effect of early pregnancy on a previous lower segment cesarean section scar.

OBJECTIVE: To summarize the manifestation, diagnosis, and early management of early pregnancy on a previous cesarean section scar. METHOD: Fifteen cases of early pregnancies implanted on previous cesarean section scars were diagnosed and treated in two obstetrical centers. RESULTS: The 15 patients had light, painless vaginal bleeding and their serum beta-subunit human chorionic gonadotropin (beta-HCG) was elevated. The interval between cesarean section and admission ranged from 6 months to 12 years (7.1+/-3.6 years). Doppler and real-time ultrasonic examinations demonstrated an enlargement of the previous cesarean section scar in the lower segment, a gestational sac or a mixed mass attached to the cicatrix, and a very thin myometrium between the gestational sac and the bladder wall. Serum beta-HCG dropped to normal in 12 of the 15 patients following treatment with crystalline trichosanthin injected into the cervix followed by oral mifepristone, intramuscular injections of methotrexate, or other appropriate treatment. Two patients underwent total hysterectomy due to massive vaginal bleeding. The remaining patient was misdiagnosed with choriocarcinoma and also had total hysterectomy. CONCLUSION: Pregnancy on a previous lower segment cesarean section scar is rare but very dangerous. Early diagnosis and effective conservative drug treatment may be instrumental in decreasing the occurrence of uterine rupture.

Adult↗
PubMed1989

Radioimmunoassay of free beta-subunit of human chorionic gonadotropin in diagnosis of high-risk and low-risk gestational trophoblastic disease.

A radioimmunoassay was performed with monoclonal antibody 1E5, which distinguishes free beta-subunit of human chorionic gonadotropin in the presence of intact human chorionic gonadotrophin. Serum samples were obtained from 68 pregnant women, 9 with hydatidiform mole who underwent spontaneous remission, 12 with hydatidiform mole who developed gestational trophoblastic disease, 5 with metastatic gestational trophoblastic disease of high-risk category, and 1 with choriocarcinoma concomitant with pregnancy. The concentrations of free beta-subunit of human chorionic gonadotropin and total beta-subunit were determined on the sera. The assay data were expressed as a ratio of nanograms of free beta-subunit per 1000 mIU of total beta-subunit. The ratios, analyzed by the Wilcoxon two-sample test, indicated a highly significant correlation between high ratios and the eventual diagnosis of high-risk gestational trophoblastic disease (p = 0.0019). This study suggests that the excessive production of free beta-subunit of human chorionic gonadotrophin may identify patients with high-risk gestational trophoblastic disease much earlier and identify gestational trophoblastic disease in patients during pregnancy.

Adult↗
PubMed1983

The beta subunit of human chorionic gonadotropin is encoded by multiple genes.

Two recombinant phage clones bearing sequences corresponding to the beta subunit of human chorionic gonadotropin (hCG beta) were isolated from a human genomic library. The beta sequences were mapped by blot hybridization of restriction digests of these phage DNAs and the nonoverlapping inserts were subcloned in pBR322 and sequenced. The nucleotide-sequencing data show that the hCG beta subunit is encoded by at least three nonallelic genes. Moreover, based on restriction analyses of human placental DNA, these genes may be linked in a single cluster with four other hCG beta-like genes. The sequenced genes all differ in their 5' flanking regions, and none of them is completely homologous in sequence to either of two hCG beta cDNA clones used here. In the translated region of one of these genes, three base substitutions result in two changes from the reported amino acid sequence. In the family of beta-containing glycoprotein hormones, the hCG beta subunit is unique in that it contains an extension of 29 amino acids at its COOH end. The DNA sequence corresponding to this region in the sequenced genes is part of a larger exon. These data show that the COOH-terminal extension does not result from splicing of the primary RNA transcript.

Amino Acid Sequence↗
PubMed1985

The diagnosis of ectopic pregnancies in cases of lower abdominal pain using beta subunit assay of human chorionic gonadotropin.

The role of beta-subunit assay of human chorionic gonadotropin (hCG) in the early and accurate diagnosis and treatment of ectopic pregnancy was evaluated prospectively in a group of 57 women who presented with lower abdominal pains. A flow scheme for diagnosis work-up based primarily on hCG beta-subunit assay resulted in no false negative result. This enabled early and conservative treatment of the condition. Ectopic pregnancy was diagnosed early in more than one third of the patients. As a result conservative treatment was performed in cases were it was required and medically possible (33% of the cases).

Abdomen↗
PubMed1988

Site-specific mutagenesis defines the intracellular role of the asparagine-linked oligosaccharides of chorionic gonadotropin beta subunit.

The beta subunit of human chorionic gonadotropin contains two asparagine (N)-linked oligosaccharides. To examine the structural and functional roles of these oligosaccharide units in vivo, we constructed mutant genes containing alterations in either the asparagine or threonine codons of the two glycosylation consensus sequences and inserted them into a eukaryotic expression vector. Wild-type and mutant CG beta proteins were expressed in Chinese hamster ovary cells alone or in the presence of native alpha subunit. Pulse-chase analysis of the beta-expressing clones showed that absence of the second N-linked sugar but not the first slows secretion 1.6-1.8-fold; absence of both N-linked units slows secretion 2-2.4-fold. Analysis of dimer clones reveals that greater than 80% of the native and glycosylation mutant CG beta subunits are secreted as dimer. However, pulse-chase analysis of these clones also reveals that the mutants completely devoid of N-linked sugars but not the single site mutants are slow to assemble with the alpha subunit. Thus, in vivo the two N-linked oligosaccharides of CG beta are critical for efficient secretion and assembly with the alpha subunit and are likely important for proper folding of the CG beta subunit.

Animals↗
PubMed1978

Human chorionic gonadotropin (beta-subunit) in the early diagnosis of ectopic pregnancy.

In 15 women with suspected ectopic pregnancy considerable amounts of beta-subunit of human chorionic gonadotropin (hCG) were detected in the serum by the radioimmunoassay technique. The diagnosis was proved by laparotomy. In another 25 suspected cases beta-hCG values were less than 1 mU/ml, and in those cases the diagnosis was excluded. The detection of the beta-subunit of hCG in the serum was found to be an excellent tool for the early diagnosis of ectopic pregnancy, thus helping to prevent the dangerous sequelae which follow in the late diagnosis of this condition. The advantage of detecting the beta-subunit of hCG rather than hCG is discussed.

Chorionic Gonadotropin↗
PubMed1997

Mass spectrometric characterization of nicked fragments of the beta-subunit of human chorionic gonadotropin.

We describe the use of an HPLC/MS technique for the characterization of nicked fragments of hCG beta-subunit. After reductive alkylation of the nicked hCG beta-subunit with vinylpyridine, endoproteinase Glu-C or trypsin was used to digest the protein to produce peptides that could be analyzed by HPLC/electrospray ionization MS. Human leukocyte elastase digestion was used to produce an experimentally nicked hCG. Two nicking sites were observed, between amino acids 42Thr and 43Arg and between 44Val and 45Leu. The former site has not been previously reported for elastase digestion. The structures of the fragments were confirmed by HPLC/MS after removal of the oligosaccharide by direct mass measurement and by mass determination of their proteolytic digests. Without the glycopeptidase treatment, the microheterogeneity of the two N-linked oligosaccharides could be deduced from the spectra of the proteolytic fragments. Nicking with elastase was found to alter the oligosaccharide structures. Nicked beta-subunit samples isolated from the urine of choriocarcinoma patients were also analyzed and the location of the nicking site(s) agreed with that determined by classical techniques. Important differences in the oligosaccharide structures were also observed in these samples, including the presence of triantennary oligosaccharides not found in hCG from healthy subjects. These findings demonstrate the potential of HPLC/MS for characterization of glycoprotein standard preparations.

Alkylation↗
PubMed1994

Effect of peptide nicking in the human chorionic gonadotropin beta-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors.

It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-beta subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cycliC AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the beta 44-49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the beta-intercysteine loop on recombinant human TSH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

beta-Subunit of human chorionic gonadotropin, ultrasound, and ectopic pregnancy: a prospective study.

This prospective study shows that the beta-subunit of human chorionic gonadotropin (beta-hCG) "screen" and ultrasound provide for nearly 100% clinical accuracy in diagnosing ectopic pregnancy in suspected cases. During the 14 months from February, 1981, to April, 1982, 81 consecutive patients believed to have ectopic pregnancies were screened. Fifty-six had a negative beta-hCG screen, thus ruling out early pregnancy complications. No false negative results were found. Twenty-seven patients had a positive screen, and 16 of these had an ectopic pregnancy. Twenty of the 27 patients with a positive beta-hCG screen underwent pelvic ultrasound examination. All of those with a positive beta-hCG screen and no intrauterine pregnancy on ultrasound had ectopic pregnancies. With the use of these clinical aids, morbidity and tubal damage are reduced because delay in operating upon those with ectopic pregnancy is avoided. Unnecessary operation is avoided in those patients who do not have an ectopic pregnancy.

Adolescent↗
PubMed1982

Monoclonal antibodies against immunodeterminants associated with the alpha and beta subunits of human chorionic gonadotropin.

Spleen cells of BALB/c mice immunized with human chorionic gonadotropin (HCG), a glycopeptide hormone composed of two nonidentical alpha and beta subunits, were fused with NS-1 mouse myeloma cells. Two hybrid cell lines, cone PC2 and clone PD3 secreting monoclonal antibodies (McAb) to HCG were isolated. With the aid of a double antibody radioimmunoassay it was established that PC2-McAb recognizes an immunodeterminant associated with beta-HCG subunit, whereas, PD3-McAb recognizes an epitope present on the alpha-HCG subunit. Both monoclonal antibodies showed an affinity constant of approximately 5 X 10(10) L/M. Because of these immunological characteristics, only PC2-McAb specifically reacts with HCG and shows cross-reactivities of less than 0.1% to other related human glycopeptide hormones. On the other hand, using a hemagglutination test based on antibody induced agglutination of sheep red blood cells coated with HCG, it was shown that only PD3-McAb is capable of inducing a positive reaction, although both monoclonal antibodies have a similar binding capacity to the coated cells. The potential of these two new monoclonal reagents for the qualitative detection and quantitative determination of HCG in human biological fluids is discussed.

Animals↗
PubMed2004

Development of human chorionic gonadotropin subunit-beta promoter-based toxic gene therapy for testicular cancer.

OBJECTIVES: To develop a new toxic gene therapy using the tissue-specific human chorionic gonadotropin-beta (hCG-beta) promoter for testicular cancer. Although most patients presenting with disseminated testicular tumor are cured through the use of chemotherapy with or without surgery, those patients with relapse after initial therapy present a difficult clinical problem. The serum tumor marker hCG-beta is frequently elevated in patients with testicular cancer, and the pretreatment and post-treatment levels of serum hCG-beta are highly predictive of treatment outcome. METHODS: Human testicular embryonal carcinoma cell line, NEC 8, a human prostate cancer cell line, PC-3, and a human bladder cancer cell line, WH, were used in this study. A transient expression experiment was used to analyze the activity of a 729-bp hCG-beta promoter in all three cell lines. A recombinant adenovirus carrying thymidine kinase (Ad-hCG-beta-TK) under control of the hCG-beta promoter was generated. The tissue-specific activity of Ad-hCG-beta-TK was tested in vitro and in vivo. RESULTS: The hCG-beta promoter had significantly greater activity in the hCG-beta-producing cell line (NEC 8) than in the non-hCG-beta-producing cell lines (PC-3 and WH). In vitro, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 growth but not PC-3 or WH cell growth. In vivo, Ad-hCG-beta-TK with acyclovir significantly inhibited NEC 8 subcutaneous tumor growth in nude mice. CONCLUSIONS: In this study, we explored the possibility of developing a new therapeutic agent to target and induce the killing of testicular germ cell tumor selectively by using tissue-specific hCG-beta promoters.

Acyclovir↗
PubMed1988

[Monoclonal antibodies against the beta subunit of human chorionic gonadotropin].

The aim of investigation was creation of hybridomas, which produce monoclonal antibodies to the beta-subunit of human chorionic gonadotropin (beta-hCG), characterization of monoclonal antibodies, which necessary for hCG immunoassay in biological fluids, as an immunological methods of detection of early stage of pregnancy and choriocarcinoma. 4 hybridomas, producing monoclonal antibodies to-hCG of IgG1 isotype, were created. On the base of monoclonal antibodies, which produced by D2 hybridoma cell line, test-systems for RIA of hCG in blood serum and urine were elaborated. These test-systems can be used in medical practice for diagnosis of early stages of pregnancy and choriocarcinoma.

Animals↗
PubMed1982

Immunobiological properties of a carboxy-terminal 53-amino acid peptide of the beta subunit of human chorionic gonadotropin.

Lengthening of the carboxy terminus unique region of beta-hCG from 30 to 45 amino acids was found in previous studies to improve immunogenicity and hormone neutralization capacity. The present study was carried out to determine whether further elongation of the peptide to 53 amino acids enhances to hormone neutralization capacity without loss of specificity characteristics. The peptide 93--145 of beta-hCG with substitution of cysteines at 93, 100 and 110 by alpha-aminobutyric acid was synthesized by solid phase and conjugated to tetanus toxoid by an active ester method. Rabbit antibodies against this conjugate reacted with CTP-53 and CTP-45 with a parallel slope in anti-CTP-53-[125I]Tyr-CTP--53 radioimmunoassay system. Other CTPs, e.g. CTP-26, CTP-31 and CTP-35 competed with lower efficiency; 50% inhibition of binding was obtained with 10-100 pmol/tube with these peptides instead of 0.5 pmol/tube for the homologous CTP-53. Anti-CTP-53 reacted with both beta-hCG and hCG but around twenty times greater amount of hCG was required to give 50% inhibition of binding as compared to CTP-53. The antigen binding capacity of anti-CTP-53 was around 4000 ng/ml for CTP-53 and 25 ng/ml for hCG. The anti-CTP-53 sera retained non-cross-reactivity with hLH as determined by direct binding with [125I]hLH and by competitive inhibition of CTP-53 binding with anti-CTP-53. Anti-CTP-53 neutralized the bioactivity of hCG in the Leydig cell bioassay and in the mouse uterine weight gain assay. Anti-CTP-53 antibodies were about three times more effective than anti-CTP-45 in their capacity to neutralize the bioactivity of hCG, though still substantially poorer than anti-beta-hCG sera in this respect.

Amino Acids↗
PubMed1983

Landmarks during the first forty-two days of gestation demonstrated by the beta-subunit of human chorionic gonadotropin and ultrasound.

Prospective pregnancy evaluation through the combined use of a radioimmunoassay (RIA) for the beta-subunit of human chorionic gonadotropin (beta-hCG) and ultrasound during the first 42 days of gestation after ovulation was performed on a population asymptomatic for first-trimester spontaneous abortion. One hundred forty-six ultrasonic observations in 98 pregnancies were made with simultaneous beta-hCG RIA performed in 80 patients. The following landmarks of normal gestational growth were identified: (1) Before 26 days, beta-HCG RIA permits definitive diagnosis of growing trophoblastic tissue, and serial samples allow doubling time computation for prognosis while ultrasound shows a nonspecific increasing decidual response within the uterus; (2) between 26 and 36 days after ovulation, serial beta-hCG samples continue to give doubling time results while ultrasonic demonstration of a gestational sac is normally seen by 28 days after ovulation; (3) the lack of fetal heart motion by 42 days after ovulation or within a gestational sac with a mean diameter of greater than 30 mm was prognostic of abortion; (4) the absence of a gestational sac by 28 days after ovulation or with a beta-hCG RIA greater than 1,000 ng/ml is suggestive of an ectopic pregnancy until proved otherwise.

Abortion, Threatened↗
PubMed1986

The origin of a human chorionic gonadotropin beta-subunit-core fragment excreted in the urine of patients with cancer.

Immunoreactive human Chorionic Gonadotropin (hCG), its subunits and hCG beta-core fragment were analyzed, using Sephadex G-100 chromatography, in urine and tumour extracts from four patients with cancer. These patients were selected for investigation because they were excreting proportionally large amounts of the hCG beta-core fragment in their urine. Although 30-85% of the total immunoreactive urinary hCG was hCG beta fragment, traces of the fragment (2% of total hCG) were found in only two of the tumours and none in the other two. The predominant molecular form of hCG in the tumours was intact free beta-subunit of hCG. The conclusion is that the hCG beta-core fragment found in the urine of some patients with cancer is not a secretion product of the tumours. This fragment is very likely a peripheral degradation product of the free beta-subunit of hCG which is secreted by the tumours.

Adult↗