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Albuquerque, NM, United States

Cole L.A.,United States hCG Reference Service
Asian Pacific Journal of Reproduction | Year: 2012

Introduction: The three dimensional crystal structure of hCG has been publish by Wu et al., Lapthorn et al., and Lustbader et al. The problem is that the crystal is missing 50% of the hCG molecular weight. It is missing the 4 N-linked and the 4 O-linked oligosaccharides and β-subunit amino acid residues 113-145. Here we add back in these missing structures, and considering 11 reported consequences we predict the final structure of hCG, hyperglycosylated hCG, nicked hCG and hCG free β-subunit. Methods: The consequences of 11 report are considered. The missing structures are examined by 2 webware programs, Bioinformatics Toolkit (Max Planck Institute), and Bioinformatics and Computational Biology (IIT Delhi). Results & Discussion: Structures are proposed for hCG, hyperglycosylated hCG, nicked hCG and hCG free β-subunit, considering the charge effect that the 12 or 19 sialic acid residues may have, movement of α-subunit loop 2 and movement of β-subunit safety belt.: Nicking causes a major structural change to β-subunit loop 2. © 2012 Hainan Medical College.


Cole L.A.,United States hCG Reference Service | Butler S.A.,Middlesex University
Asian Pacific Journal of Reproduction | Year: 2012

Objective: Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG made by cytotrophoblast cell. Here we examine the role of hyperglycosylated hCG in placenta growth and invasion. Methods: JEG-3 choriocarcinoma cells and term cytotrophoblast monolayer culture were prepared. The effect of supplemental hyperglycosylated hCG and hCG was investigated. Growth of these cells was examined by increase in cell number. Invasion was investigated using Matrigel basement membrane cells. The proportion of cell invading Matrigel was determined. Results: Term cytotrophoblast cell and JEG-3 choriocarcinoma cells grew to 5 427±834 cells (109%) and 7 114±553 cells (142%). With the supplementation of hyperglycosylated hCG, they grew significantly wider to 7 633±177 cells (142%) and 10 315±1 477 cells (206%). With the supplementation of hCG they diminished to 4 227±769 cells (78%) and 5 620±657 cells (79%). Term cytotrophoblast cell and JEG-3 choriocarcinoma cells penetrated Matigel membranes to (40.0±10.0)% and (46.0±9.8)%. Hyperglycosylated hCG significantly enhanced penetration to (76.0±13.0)% and (84.0±6.6)%. hCG diminished penetration to (32.0±9.1)% and (32.0±4.5)%. Conclusions: Hyperglycosylated hCG enhances both cytotrophoblast growth and cytotrophoblast cell invasion. hCG minimally suppresses growth and invasion. © 2012 Hainan Medical College.


Cole L.A.,United States hCG Reference Service
International Journal of Gynecological Cancer | Year: 2014

Introduction: Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Methods: Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG/total hCG. Results: Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Discussion: Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases. Copyright © 2014 by IGCS and ESGO.


Cole L.A.,United States hCG Reference Service
Reproductive Biology and Endocrinology | Year: 2012

Background: hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail.Content: These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies.Conclusions: The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. © 2012 Cole; licensee BioMed Central Ltd.


Iles R.K.,St. Bartholomews Hospital | Iles R.K.,ELK Foundation for Health Research | Iles R.K.,MAP Diagnostics Ltd. | Cole L.A.,United States hCG Reference Service | And 2 more authors.
International Journal of Molecular Sciences | Year: 2014

The analysis of human chorionic gonadotropin (hCG) in clinical chemistry laboratories by specific immunoassay is well established. However, changes in glycosylation are not as easily assayed and yet alterations in hCG glycosylation is associated with abnormal pregnancy. hCGβ-core fragment (hCGβcf) was isolated from the urine of women, pregnant with normal, molar and hyperemesis gravidarum pregnancies. Each sample was subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis following dithiothreitol (DTT) reduction and fingerprint spectra of peptide hCGβ 6-40 were analyzed. Samples were variably glycosylated, where most structures were small, core and largely mono-antennary. Larger single bi-antennary and mixtures of larger mono-antennary and bi-antennary moieties were also observed in some samples. Larger glycoforms were more abundant in the abnormal pregnancies and tri-antennary carbohydrate moieties were only observed in the samples from molar and hyperemesis gravidarum pregnancies. Given that such spectral profiling differences may be characteristic, development of small sample preparation for mass spectral analysis of hCG may lead to a simpler and faster approach to glycostructural analysis and potentially a novel clinical diagnostic test. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

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