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Biomedical subjects

G Coukos

Publications and source records attributed to G Coukos.

At least 37 records · Page 2Linked to original sources
PubMed1999

Complete hydatidiform mole. A disease with a changing profile.

OBJECTIVE: To retrospectively evaluate the clinical presentation of complete molar pregnancies in an academic primary obstetrics and gynecology practice over the past decade. STUDY DESIGN: All cases of abnormal pregnancy presenting to our institution during the first half of gestation were identified through a computerized database. Clinical presentation and course of complete moles were analyzed. RESULTS: Twenty-four complete molar pregnancies were identified among 2,431 abnormal early gestations (1%). The patients' mean age was 24.5 years, and the mean gestational age was 9.5 weeks of amenorrhea (range, 8-25). Seventy-five percent of the patients presented with vaginal bleeding and 54% with excessive uterine size. None had hyperemesis gravidarum, preeclampsia, clinical hyperthyroidism or ovarian enlargement. All patients had abnormally elevated serum beta-hCG. Transvaginal ultrasound was diagnostic in more than half the patients, while it was suggestive of the diagnosis in the remainder. One patient experienced postevacuation trophoblastic embolization and developed persistent gestational trophoblastic disease. CONCLUSION: Due to the routine use of transvaginal ultrasound and serum beta-hCG in the workup of early gestational abnormalities, complete molar pregnancy rarely presents today with the traditional signs and symptoms. Despite their absence, the potential for persistent trophoblastic disease still exists, and careful follow-up is warranted.

Adult↗
PubMed1998

Chemotherapy resistance in ovarian cancer: new molecular perspectives.

OBJECTIVE: To provide the obstetrician-gynecologist with the recent advances in mechanisms of chemotherapy resistance in ovarian cancer. DATA SOURCES: A computerized search of articles published through September 1997 was performed on the MEDLINE Ovid and Cancerlit databases. Additional references were identified from the reference section of all selected papers. METHODS OF STUDY SELECTION: All identified references were evaluated as to their relevant contribution to our understanding of the basic mechanisms underlying the response to chemotherapy, the development of chemotherapy resistance in ovarian cancer, and possible strategies for therapy. TABULATION, INTEGRATION, AND RESULTS: One hundred sixteen references were reviewed. A brief summary of the classic concepts on resistance to cisplatin and paclitaxel is provided, followed by a description of the basic mechanisms governing apoptosis and cell cycle arrest as well as their involvement in cell response to chemotherapy and the development of chemoresistance. Finally, a brief summary of the molecular alterations described in ovarian cancer, together with hypothetic strategies for gene-targeted therapy, are reported. CONCLUSION: Cisplatin or paclitaxel chemotherapy induces arrest of the cell cycle or apoptosis in ovarian cancer cells. Tumor suppressor genes such as p53 play a paramount role in mediating this response and p21wAF1/CIP1 is a major mediator of p53-induced arrest of the cell cycle. Molecular alterations involving these tumor suppressor genes are related to the development of resistance to chemotherapy and represent possible targets for gene therapy in ovarian cancer.

Antineoplastic Agents↗
PubMed1998

Integrins, endometrial maturation, & human embryo implantation.

Cell-cell and cell-extracellular matrix interactions are fundamental processes involved in cell migration and tissue remodeling. Both the cyclic regeneration of the human endometrium during the menstrual cycle as well as the process of embryo implantation involve such dynamic interactions. It has become quite clear that integrin adhesion molecules expressed on the surface of cells play critical roles in the transmission of signals from the extracellular milieu to the cells. It is these signals that presumably regulate the behavior of these cells during major morphogenetic processes. In recent years, work in human endometrium and trophoblasts has uncovered both the regulated and constitutive expression of integrin subunits and their extracellular matrix ligands in these tissues. In addition, attempts have been made to correlate pathological states related to either infertility or abnormal pregnancy to the aberrant expression of several of these integrins. The purpose of the present review is to describe briefly our present state of knowledge of the expression of integrins in human endometrium and trophoblasts and provide the reader with the necessary background needed to understand, at the cellular and molecular levels, processes in reproduction such as embryo implantation.

Embryo Implantation↗
PubMed1998

Platelet-endothelial cell adhesion molecule-1 is expressed by a subpopulation of human trophoblasts: a possible mechanism for trophoblast-endothelial interaction during haemochorial placentation.

The terminal event in the establishment of the haemochorial placenta in the human is the invasion of trophoblasts into the maternal vessels, a process in which trophoblasts interact directly with the vascular endothelium and degrade the vascular basement membrane and the tunica elastica of the vessels. To further understand this heterotypic cellular interaction, we investigated the expression by human trophoblasts of the vascular cell adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-1) as a possible mediator of the adhesive interaction between trophoblasts and endothelium. In vitro, human trophoblasts were found to express PECAM-1 mRNA and protein. Indirect immunofluorescence indicated a diffuse staining pattern, which was most intense in a subpopulation of trophoblast cells. Co-incubation of trophoblasts with endothelial cells showed interaction between these two cell types with strong expression of PECAM-1 at points of trophoblast-endothelial cell contact, suggesting that this cell adhesion molecule participates in this heterotypic cell interaction. Immunohistochemical localization of PECAM-1 in chorionic villi and first trimester implantation sites showed that, in vivo, only extravillous interstitial and endovascular trophoblasts were positive. In first trimester placentae, villous trophoblast and extravillous trophoblast in other locations than around or within the decidual vessels did not express this molecule. In term placentae, villous trophoblast did not express these adhesion molecules except for two specimens examined. This study demonstrates that PECAM-1 is expressed by a subset of human trophoblasts in vitro and in vivo. Its tissue localization suggests that PECAM-1 is important in mediating the adhesive interaction between trophoblasts and maternal vascular endothelium during the process of haemochorial placentation. Regulation of PECAM-1 expression by human trophoblasts may play a critical role in normal and abnormal vascular invasion during implantation and placentation.

Cell Adhesion↗
PubMed1998

Macrophage-colony stimulating factor (M-CSF) regulates the expression of fibronectin and its alpha5 integrin receptor in human trophoblasts.

Macrophage-colony stimulating factor (M-CSF, CSF-1) is secreted by human trophoblasts as well as endometrial cells, while its receptor c-fms is abundantly expressed by the extravillous trophoblasts anchoring the placenta to the uterus, suggesting a role for M-CSF at the maternal-fetal interface. We investigated the effect of M-CSF on the expression of fibronectin and its receptor, the alpha5 integrin, in human trophoblasts. Exposure of trophoblasts to M-CSF produced a two to three-fold increase in fibronectin and alpha5 mRNA abundance at both 24 and 72 hours of culture. A dose-dependent increase in cellular fibronectin secretion into the culture medium was detected at both time points. Immunocytochemistry showed co-localization of cellular fibronectin and alpha5 in the cells, suggesting that attachment of trophoblasts to fibronectin is mediated in part by the alpha5beta1 integrin. We conclude that M-CSF increases fibronectin expression and secretion by the human trophoblasts, and up-regulates its specific receptor, the alpha5 integrin. We hypothesize that M-CSF may partake in the autocrine/paracrine mechanisms regulating trophoblast invasion during implantation.

Antigens, CD↗
PubMed1994

Human immunodeficiency virus type 1 causes productive infection of macrophages in primary placental cell cultures.

To characterize the role of the placenta in vertical transmission of human immunodeficiency virus type 1 (HIV-1), the susceptibility of primary human placental cultures and of transformed trophoblast cell lines to infection by several HIV-1 isolates was examined. Placental cultures supported the replication of all strains tested, including lymphocyte-, macrophage-, and amphotropic isolates. All viruses replicated to modest levels, with production of both viral antigen and infectious virus in the culture supernatants. Placental cells demonstrated a pattern of permissiveness for HIV-1 isolates distinct from that seen with lymphocytes, blood-derived macrophages, or T cell lines. Immunofluorescent staining showed that 5%-10% of the cultured placental cells expressed viral antigens, and double labeling revealed that the HIV-positive cells were macrophages not trophoblasts. None of the trophoblast cell line (JEG-3, Jar, BeWo, HP-W1) could be infected by HIV. These results support the hypothesis that infection of the placenta could play a role in maternofetal transmission of HIV-1 and suggest that the placental macrophage is likely to be the primary cell type responsible.

Cell Line, Transformed↗
PubMed1994

Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and the 39-kd receptor-associated protein in human trophoblasts.

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and its 39-kd receptor-associated protein (RAP) were identified by indirect immunofluorescence in human extravillous and villous trophoblast cells at different stages of pregnancy. The alpha 2MR/LRP was detected in invading trophoblast cells and in some instances these invading cells did not express RAP. In chorionic villi of first and second trimester placenta, alpha 2MR/LRP and RAP were found in cytotrophoblast and syncytiotrophoblast. With advancing pregnancy alpha 2MR/LRP became primarily localized to the apical surface of the syncytiotrophoblast, while RAP was present in the cytoplasm. Villous cytotrophoblast cells lost both proteins by the third trimester. Isolated cytotrophoblast cells that undergo spontaneous differentiation into syncytiotrophoblast in culture increased expression of both alpha 2MR/LRP and RAP. With syncytium formation, alpha 2MR/LRP became localized to the plasma membrane in cup-like structures. Changes in the mRNAs for alpha 2MR/LRP and RAP paralleled the changes in relative abundance of the proteins assessed by immunofluorescence. cAMP treatment suppressed both alpha 2MR/LRP and RAP in the cultured trophoblasts, but alpha 2MR/LRP was reduced to a greater extent than RAP. We conclude that alpha 2MR/LRP and RAP are developmentally regulated in human trophoblast cells, that the temporal and spatial patterns of expression of these proteins can be dissociated, and that cAMP modulates both alpha 2MR/LRP and RAP in human trophoblast. The patterns of alpha 2MR/LRP and RAP expression in trophoblast cells are consistent with roles for the receptor in trophoblast invasion and transport of molecules across the syncytiotrophoblast.

Carrier Proteins↗
PubMed1992

Regulated expression of the trophoblast alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Differentiation and cAMP modulate protein and mRNA levels.

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) has several ligands including activated alpha 2-macroglobulin, pregnancy zone protein, and very low density lipoproteins enriched with apolipoprotein E. The diversity of ligands suggests a role for the alpha 2MR/LRP in a variety of processes including tissue remodeling and lipoprotein metabolism. We examined alpha 2MR/LRP in placental trophoblasts, invasive cells that also function in lipid transport and cholesterol metabolism. alpha 2MR/LRP protein was localized by immunohistochemistry in the syncytiotrophoblast of term placenta. Cytotrophoblasts did not stain prominently. alpha 2MR/LRP (protein and message) in primary cultures of human trophoblast cells increased as cytotrophoblasts differentiated into syncytiotrophoblast. 8-Bromo-cAMP prevented this increase and suppressed alpha 2MR/LRP expression. The cyclic nucleotide had similar suppressive effects on alpha 2MR/LRP in BeWo choriocarcinoma cells. In contrast, low density lipoprotein receptor gene expression was increased. We conclude that: 1) there is a differentiation-dependent pattern of alpha 2MR/LRP expression in the human trophoblast; 2) cAMP negatively regulates alpha 2MR/LRP; 3) there is an inverse relationship between alpha 2MR/LRP and low density lipoprotein receptor gene expression in trophoblast cells.

Base Sequence↗
PubMed1992

Efficacy of hormone replacement therapy in postmenopausal women with oral discomfort.

The increase in incidence of oral discomfort among women in a menopause is probably due to hormone modifications. This study evaluated the efficacy of hormone replacement therapy in 27 postmenopausal patients, aged 48 to 58 years, with oral discomfort and no local irritants and in 47 postmenopausal women with no oral discomfort. Patients were treated with conjugated estrogens for 21 days and medroxyprogesterone acetate from day 12 through day 21. Hormone-replacement therapy had no effect on oral cytology in the 40 symptom-free postmenopausal women compared with a group of 47 postmenopausal women who had no oral symptoms and were not treated. Hormone-replacement therapy relieved symptoms and improved oral cytohormonal features in 15 of 27 patients with symptoms. Nuclear estrogen receptors were found by immunohistochemical assay in 8 of 10 randomly selected patients with symptoms who responded to hormone-replacement therapy, but not in 2 patients who did not benefit from hormone-replacement therapy. Estrogen receptors were also found in 6 of 10 fertile women with no oral disease. Our results suggest that oral discomfort may be related to steroid hormone withdrawal only in some postmenopausal women and that replacement therapy may improve the clinical picture and cytologic features in this group of patients. Immunohistochemical identification of estrogen receptors may help to identify patients for whom hormone-replacement therapy may be beneficial.

Burning Mouth Syndrome↗
PubMed1992

Effects of growth hormone administration in addition to gonadotrophins in normally ovulating women and polycystic ovary syndrome (PCO) patients.

Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation induction with gonadotrophins or growth hormone plus gonadotrophins. Growth hormone supplementation enhanced the ovarian response to gonadotrophins, and significantly increased follicular fluid IGF-I in both groups, without affecting follicular fluid epidermal growth factor; growth hormone supplementation significantly decreased follicular fluid androstenedione in both groups.

Adult↗
PubMed1992

Sperm retrieval for direct intraperitoneal insemination in a diabetic with retrograde ejaculation. A case report.

Retrograde ejaculation is an uncommon form of male infertility. It may occur in diabetics from neuropathy involving the sympathetic fibers innervating the bladder neck. Treatment of infertility in these cases is with artificial homologous insemination. Several techniques for semen recovery from the bladder have been proposed. This paper describes a case of twin pregnancy following direct intraperitoneal insemination (DIPI) of semen retrieved from a diabetic man with retrograde ejaculation. Retrieval of semen was performed in this case by spontaneous voiding of urine after the introduction of a suitable medium into the bladder and before ejaculation. The quality of the semen was examined after spontaneous urination before DIPI. The poor quality of the spermatozoa induced us to introduce into the bladder a suitable medium before ejaculation and sperm recovery.

Administration, Intravesical↗
PubMed1991

Follicular fluid steroid and epidermal growth factor content, and in vitro estrogen release by granulosa-luteal cells from patients with polycystic ovaries in an IVF/ET program.

The follicular fluid (FF) content of androgens, estrogens and epidermal growth factor (EGF) has been evaluated in a group of patients with policystic ovary disease (PCO) and in one of normally-ovulating infertile women (NOW) in an IVF/ET program. The in vitro response to follicle-stimulating hormone (FSH) has been also evaluated in granulosa luteal cells from the same patients. PCO patients showed significantly higher FF androstenedione (delta 4) and testosterone (T) and similar FF estrone (E1) and 17 beta-estradiol (E2) levels compared to controls. In vitro production of E1 and E2 by granulosa luteal cells from PCO patients and from controls were overlapping and their response to FSH was similar. These data indicate a normal intrinsic potential aromatase activity in ovaries from PCO patients stimulated with gonadotropins and suggest that PCOs do not derive from inherent ovarian aromatase deficiency. Increased FF androgen content following gonadotropin stimulation may result from theca cell hyperactivity and androgen accumulation in the follicular antrum of rescued hyperandrogenic follicles as well as from inhibitory factors that may inhibit aromatase activation in vivo, partially counteracting the effect of gonadotropins. FF EGF levels were significantly higher in the group of PCO patients compared to those of NOW. EGF may play a role in blunting the in vivo response of granulosa cells to gonadotropins.

Androstenedione↗
PubMed1991

Pregnancy following regression of uterine submucosal leiomyoma with GnRH therapy; a case report.

A patient with a history of two spontaneous abortions, at the 16th and 20th week, respectively, and one intra-uterine fetal death at the 26th week of gestation was investigated. The sole abnormal condition that could be evidenced was a submucosal leiomyoma of 56 mm in diameter in the uterine fundus. Administration of gonadotropin/releasing hormone analog (GnRHa) for 10 months resulted in complete disappearance of myoma. Direct intraperitoneal insemination following induction of ovulation resulted in pregnancy. In a patient harboring uterine leiomyomas, adversely affecting conception and pregnancy outcome, GnRHa treatment may be an initial approach allowing to avoid pelvic surgery. As the beneficial effect of GnRHa might be temporary, assisted reproduction procedures might anticipate conception.

Abortion, Spontaneous↗
PubMed1991

Follicular fluid lipoproteins in preovulatory period and their relationship with follicular maturation and progesterone production by human granulosa-luteal cells in vivo and in vitro.

Follicular fluid (FF) lipoprotein content was evaluated in an in vitro fertilization/embryo transfer and gamete--intrafallopian--transfer program and correlated to follicular and oocyte maturation. Moreover, the in vitro progesterone response of granulosa-luteal cells from 10 patients to high-density lipoprotein (HDL) and to low-density lipoprotein (LDL) was assessed. Most FFs contained only HDL. Sixteen out of 97 FFs contained also very low levels of LDL and very-low-density lipoprotein (VLDL). The presence of LDL was associated to features of follicle and oocyte hypermaturity. LDL alone induced a much more potent increase of progesterone (P) release by granulosa-luteal cells than HDL alone, and the HDL partially reversed the potent effect of LDL. It is concluded that in late follicular phase HDL maintains P release by granulosa cells at a low rate and prevents a potent stimulation of P production by LDL which might cross the maturating blood-follicle barrier, until increasing passage of LDL in FF decreases the HDL:LDL ratio and the action of LDL becomes prominent.

Female↗
PubMed1991

Clinical use of growth hormone-releasing factor for induction of superovulation.

A consistent body of in vivo and in vitro evidence suggests that insulin-like growth factor-I (IGF-I) and possibly growth hormone (GH) play a stimulatory role in the regulation of the ovarian follicular cycle. Administration of GH in protocols of induction of superovulation gave promising results. In the present study, 10 patients with a previously normal response to gonadotrophins were administered s.c. GH-releasing factor (GRF) combined with gonadotrophins for superovulation induction in an in-vitro fertilization/embryo transfer-gamete intra-Fallopian transfer (IVF/ET-GIFT) programme. Administration of GRF was followed by shortening of the stimulatory cycle and reduction of the total number of gonadotrophin ampoules utilized per patient relative to a previous stimulatory cycle with gonadotrophins alone. A significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately following GRF administration throughout the GRF cycle suggest that GRF supported the ovarian response to gonadotrophins through stimulation of the GH-IGF-I axis. A possible direct effect of GRF is discussed. Before employing GRF for superovulation in infertile patients, the pituitary GH response to provocative stimuli should be evaluated on an individual basis.

Adult↗
PubMed1991

Doppler velocimetry in prolonged pregnancy.

Eighty-two patients at 287 days' gestation or longer were tested by nonstress test (NST), amnioscopy, ultrasound assessment of amniotic fluid volume, and Doppler velocimetry. Several maternal and fetal arteries were analyzed: uterine, umbilical, descending thoracic aorta, renal, and middle cerebral. During the study, other maternal-fetal functional indices were recorded: hPL, estriol, hematocrit, platelets, mean platelet volume, and uric acid. No abnormalities were found in the uterine, umbilical, middle cerebral, thoracic descending aorta, and renal artery velocimetry in post-dates gestations. However, a significant reduction of the time-averaged mean velocity in the descending thoracic aorta was associated with an increased incidence of oligohydramnios, meconium-stained fluid, abnormal NST, and cesarean delivery for fetal distress. The present study suggests that serial Doppler flow measurements of mean velocity of the fetal descending thoracic aorta may be a simple and rapid technique for identifying prolonged pregnancies at increased risk for perinatal complications.

Adult↗