Publications by authors named "Verhage H"

The light microscopic distinction between complex atypical hyperplasia (CAH) and invasive endometrioid carcinoma (UEC) on endometrial sampling is problematic and often has significant clinical implications. Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. We used the previously described Pten(+/-); Mlh1(-/-) mouse model.

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Purpose: Lesions in the endometrium are difficult to differentially diagnose. The present study examined whether oviduct-specific glycoprotein is differentially expressed in normal, hyperplastic, and malignant endometrium.

Experimental Design: The expression of oviduct-specific glycoprotein was characterized by immunohistochemical methods with whole sections of endometrium from 90 women.

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Objective: With neoplastic progression, the precursor of epithelial ovarian cancers, the ovarian surface epithelium (OSE), undergoes Mullerian differentiation, usually of the oviductal type. The aim of this study was to examine the expression of oviduct-specific glycoprotein (OGP), a marker of normal oviductal epithelium, for use as a diagnostic or prognostic marker for ovarian cancer.

Methods And Materials: Immunohistochemical analysis for OGP was performed on 389 ovarian tumors and 19 normal ovaries, as well as 433 cases representing 45 normal tissues and 51 benign and malignant tumor types from 37 different tissues.

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The goal of this study was to determine if differences exist between in vivo vs. in vitro OGP association with the ZP and to quantitate those differences. Ovarian oocytes were harvested 12.

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The purpose of this study was to determine the effect of a partially purified bovine oviductal glycoprotein (bOGP) on fertilization rates of bovine oocytes. The effect of albumin (control protein) or bOGP at 100 micrograms ml-1 during the 16-18 h fertilization period was evaluated in a standard IVF system using a sperm concentration between 0.5 and 0.

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The biological function of uterine endometrial secretory proteins in the primate remain to be elucidated. In general, during the luteal phase and under progesterone dominance, the glandular epithelial cells synthesize and secrete a number of proteins. Of these, placental protein 14 (PP14; now referred to as glycodelin) and insulin-like growth factor binding protein-1 (IGFBP-1) are the best characterized.

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The baboon oviductal epithelium differentiates into a tall columnar epithelium consisting of ciliated and secretory cells during the follicular phase of the menstrual cycle in response to rising oestradiol levels. The apical tips of these secretory cells are filled with membrane-bound secretory granules. During the luteal phase when progesterone levels are elevated, the epithelium regresses and deciliation occurs.

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In vitro studies indicate that glycodelin (PP14) synthesis by the human endometrium increases dramatically at the time of implantation and early pregnancy. It has been postulated that this protein may have an immunosuppressive function. Due to the limitations associated with in vivo studies in the human, this study was undertaken to study the regulation of the baboon glycodelin homolog in vivo during the menstrual cycle and early pregnancy.

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Problem: The effect of antibodies generated against hamster oviductal glycoprotein (OGP) on sperm binding to the zona pellucida (ZP) was evaluated.

Method Of Study: Antibodies against a 17-amino-acid sequence of the OGP core protein (amino acids 52-68) and the denatured hamster OGP protein were generated, characterized, and tested in an in vitro sperm binding assay.

Results: Sperm binding was significantly decreased (P < 0.

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The objective of this study was to detect and characterize a secreted oviduct-specific glycoprotein (OGP) in the rhesus macaque (Macaca mulatta) and to compare the characteristics of this OGP to those previously characterized in baboons and women. Oviducts were obtained from untreated ovariectomized rhesus and from ovariectomized rhesus either treated with estradiol (E2) for 14 days or treated sequentially with E2 for 14 days and then with E2 plus progesterone (P4) for an additional 14 days. Segments of oviducts were either fixed for morphological analysis, cultured for OGP synthesis and release, or frozen for RNA analysis.

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This study was undertaken to determine the immunocytochemical localization of transforming growth factor alpha, epidermal growth factor and epidermal growth factor receptor in the endometrium of ovariectomized cats treated with oestradiol-17 beta and/or progesterone and in the endometrium and placenta of pregnant cats. Specific immunostaining was observed for all three antibodies. Moderate immunostaining for transforming growth factor alpha was observed in the epithelium of ovariectomized and oestrogen-treated cats.

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The secretory cells of the oviductal epithelium secrete a high-molecular-weight glycoprotein (OGP). OGPs from different mammalian species show similar immunological characteristics, their cDNAs show high homologies, and they associate with the zona pellucida of oviductal oocytes in vivo. The purpose of this study was to determine the effect of OGP obtained from different species on the binding of hamster sperm to hamster oocytes.

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At the time of ovulation the lining epithelium of the mammalian oviduct consists of columnar ciliated and secretory cells. These mature cells are dependent on ovarian steroids in carnivores. Oestradiol induces differentiation of these cells and maintains their mature functional state, and progesterone induces dedifferentiation.

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Our objective in this study was to complete the sequence of the baboon oviductal glycoprotein, examine the hormonal regulation of the oviductal glycoprotein mRNA, and determine whether there was a regional variation within the oviduct in the level of oviductal glycoprotein mRNA expression. Finally, because of the structural similarity of the amino terminal end of the oviductal glycoprotein to chitinases, we sought to determine whether the oviductal glycoprotein functions as a glycosyl hydrolase. The total transcript length of the baboon oviductal glycoprotein was determined to be 2228 nucleotides in length plus a poly(A) tail.

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The objectives of this study were 1) to determine whether or not human and baboon oviduct-specific glycoproteins (human OGP, baboon OGP) would associate with ovarian oocytes during in vitro incubation in a manner similar to that detected in vivo for oviductal oocytes and 2) to determine whether the association of OGP with ovarian oocytes influenced sperm binding. In vitro association of OGP with ovarian oocytes was assessed by indirect immunofluorescence assay using a polyclonal antibody prepared against human or baboon OGP. Human and baboon ovarian oocytes incubated in culture media containing OGP showed association of OGP with the zona pellucida (ZP) as detected by bright fluorescence.

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In order to test the hypothesis that the baboon conceptus/placenta regulates the synthesis of specific proteins in the endometrium, we developed a simulated-pregnant baboon model. Baboons (n=2-6/group) were treated with increasing amounts of human chorionic gonadotrophin (hCG) for 10 or 12 days beginning on day 6 or 7 PO. Uterine tissues were obtained at day 18 PO following 12 days of hCG treatment.

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The major objective of this study was to examine the hormonal regulation of a human oviduct-specific glycoprotein (huOGP) throughout the menstrual cycle and in all regions of the human oviduct. Regulation of synthesis and secretion was examined at both the protein (Western immunoblots and immunocytochemistry) and mRNA (Northern and slot blots) levels and correlated with changes in the morphological features of the oviductal epithelial cells throughout the cycle. Immunoblot analysis of oviductal fluid and explant culture media from all regions of the oviduct demonstrated that huOGP is primarily found during the follicular stage of the cycle and is not present in serum, follicular fluid, or uterine endometrium.

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The objective of this study was to investigate the localization and hormonal regulation of smooth muscle myosin II (SMM II) and alpha smooth muscle actin (alpha SMA) in the baboon uterus, since cytoskeletal proteins are involved in secretory function and morphological transformation. Uterine tissue was obtained from baboons 1) during the menstrual cycle, 2) following steroid treatment of ovariectomized baboons, 3) during pregnancy (Days 14-60 postovulation [PO]), and 4) during simulated pregnancy (Days 18-32 PO). Tissues were processed for immunocytochemical localization of SMM II or alpha SMA with specific polyclonal or monoclonal antibodies, respectively.

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The primate endometrium undergoes distinct morphological changes during the menstrual cycle. These alterations are regulated by the steroid hormones, estrogen and progesterone. Several lines of evidence suggest that some of these hormonally induced changes may be modulated by growth factors.

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Objective: Marked alterations occur in the synthesis of endometrium-specific proteins during the first third of pregnancy in the baboon. Because epidermal growth factor (EGF) expression has been associated with proliferation in the human and mouse endometrium, we hypothesized that EGF, transforming growth factor-alpha (TGF alpha), and EGF receptor (EGF-R) expression in baboon endometrium may be modulated by the early invasive trophoblast and play a role in decidualization of the endometrial stroma.

Methods: Endometrial tissue was obtained from cycling baboons (n = 4-5 per time point), ovariectomized steroid-treated baboons (n = 4 per group), or from pregnant baboons on days 18-60 of pregnancy (n = 2-4 per group).

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Objectives: Polypeptide growth factors may modulate the actions of estrogen (E2) and progesterone (P) in reproductive tissues in an autocrine/paracrine manner. The objective of this study was to determine whether the baboon oviduct contains epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor (EGF-R) and whether changes in their expression are correlated with various hormonal states.

Methods: Oviductal tissue was obtained from adult female baboons (Papio anubis) after oophorectomy and steroid treatment, and during the menstrual cycle.

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A 120-kDa oviduct-specific glycoprotein is synthesized and secreted into the oviductal lumen during estrogen dominance in the human. The objective of this investigation was to clone, sequence, and characterize the cDNA to this core protein. Rapid amplification of cDNA ends was used to clone a contiguous 3' CDNA end and 5' cDNA end.

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This study was undertaken to determine whether insulin-like growth factor binding protein-1 (IGFBP-1) was synthesized by the cat uterus and placenta during implantation and pregnancy. Endometrial and placental tissue explants from pregnant, pseudopregnant, and ovariectomized steroid-treated cats were cultured in the presence of 35S-methionine. Culture media proteins were separated by one-dimensional (1-D) and two-dimensional (2-D) SDS-PAGE, transferred to nitrocellulose, and immunostained using a rabbit polyclonal antibody against baboon IGFBP-1 and a murine monoclonal antibody to human IGFBP-1.

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Retinols and retinoic acid (vitamin A) are essential for embryonic development; they are transported in circulation bound to retinol-binding protein (RBP). RBP has been shown to be synthesized in extrahepatic sites, i.e.

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