Coagulation and fibrinolysis in intact hydatidiform molar pregnancy.
Tests of coagulation, fibrinolysis, and platelet function were performed in 17 patients with intact molar pregnancies. Women with intact molar pregnancies had higher fibrinogen factor VIII, and fibrinogen degradation products, concentrations and lower prothrombin, factor X, plasminogen, and plasminogen activator concentrations than controls with normal pregnancies. They also had reduced platelet counts and thromboelastographic values, which indicated hypocoagulability. These results suggest that intravascular coagulation occurs in intact hydatidiform molar pregnancies. (+info)
The ultrastructure of fibromyomatous myometrium and its relationship to infertility.
The aim of this study was to determine whether the ultrastructure of the non-neoplastic myometrial portion (host myometrium) of fibromyomatous uteri is normal or abnormal when compared to that of fibromyomata and normal myometria. Myometrial samples from 23 normal and 54 fibromyomatous uteri were examined at the ultrastructural level using standard electron microscopy techniques. Ultrastructural abnormalities of certain cellular organelles were noted in myocytes of fibromyomata but not in those of normal or host myometria. The sarcolemmal dense bands of host myometrial myocytes were of significantly greater length than those of normal myometria, but not significantly different to those of fibromyomata. Consequently, the numbers of caveolae in host myometria and fibromyomata are conceivably decreased in comparison to normal myometria. Host myometria can be, therefore, considered to be structurally abnormal. The specific structural abnormality noted may affect calcium metabolism in these tissues by causing a decrease in the cellular calcium extrusion mechanism and thus raising intracellular calcium concentrations. Such an abnormality may provide an answer, in terms of contraction abnormalities, for the unexplained infertility that occurs in a small percentage of symptomatic myomatous patients. (+info)
Oxytocin and vasopressin receptors in human and uterine myomas during menstrual cycle and early pregnancy.
The purpose of this study was to determine the specificity and concentration of oxytocin (OT) and arginine vasopressin (AVP) binding sites in non-pregnant (NP) human and rhesus monkey endometrium, myometrium and fibromyomas, and to determine the cellular localization of OT receptor (OTR). Besides [3H]AVP, [125I]LVA, a specific VP1 receptor subtype antagonist, was used to determine vasopressin receptor (VPR) concentrations. Samples were obtained from 42 pre-menopausal and three pregnant women (5, 13 and 35 weeks gestation), and several NP and pregnant monkeys. Specificity of binding was assessed in competition experiments with unlabelled agonists and antagonists of known pharmacological potency. Cellular localization of OTR was determined by immunohistochemistry. In NP human uterine tissues, [3H]AVP was bound with higher affinity and greater binding capacity than [3H]OT, whereas in pregnant women and in NP and pregnant rhesus monkeys, uterine OT binding capacity was greater. OT and AVP binding sites discriminated very poorly between OT and AVP; [125I]LVA binding sites were more selective than [3H]AVP. Their ligand specificity and binding kinetics indicated the presence of two distinct populations of binding sites for OT and AVP in primate uterus. Endometrium of NP women and monkeys had low OTR and VPR concentrations. Myometrial and endometrial OTR and VPR were down-regulated in midcycle and in early human pregnancy, they were up-regulated in the secretory phase and second half of pregnancy. Immunoreactive OTR in NP uterus was localized in patches of myometrial muscle cells and small numbers of endometrial epithelial cells. (+info)
Adenosquamous carcinoma of the endometrium.
An adenosquamous carcinoma of the endometrium is one which contains both malignant glandular and malignant squamous components; such tumours are considered rare in Britain but are thought to account for nearly one-third of all endometrial neoplasms in the United States. A survey of 675 cases of endometrial cancer seen during the period 1956-75 showed that the incidence of adenosquamous carcinoma was 5%, an incidence that remained static during this 20-year period. The principal difficulties encountered in the diagnosis of these neoplasms are in identifying the squamous component as such and in differentiating it from benign metaplastic squamous epithelium. The prognosis for patients with an endometrial adenosquamous carcinoma is very much worse than for women with a pure adenocarcinoma, and because these neoplasms are often wrongly identified it is possible that the currently accepted prognoses for both pure adenocarcinoma and adenoacanthoma of the endometrium may have to be revised. There appears to be a true variation in the incidence of this neoplasm between Britain and the United States. (+info)
Heparin inhibits proliferation of myometrial and leiomyomal smooth muscle cells through the induction of alpha-smooth muscle actin, calponin h1 and p27.
Mast cells are widely distributed in human tissues, including the human uterus. However, the function of mast cells in uterine smooth muscle has not been clearly established. Mast cells possess secretory granules containing such substances as heparin, serotonin, histamine and many cytokines. To help establish the role of mast cells in the human myometrium, the action of heparin was investigated using smooth muscle cells (SMC) from normal myometrium and from leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by heparin treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under heparin treatment. Western blotting analysis showed that markers of SMC differentiation such as alpha-smooth muscle actin (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by heparin, whereas cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not changed. Taken together, these results indicate that heparin inhibits the proliferation of myometrial and leiomyomal SMC through the induction of alpha-SMA, calponin h1 and p27. We suggest that heparin from mast cells may induce differentiation in uterine SMC and may influence tissue remodelling and reconstruction during physiological and pathophysiological events. (+info)
CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells.
The CD9 molecule is expressed on human extravillous trophoblasts, which invade the endometrium during implantation and placentation. To elucidate the role of CD9 in trophoblastic function, we investigated the expression of CD9 protein and mRNA in BeWo cells, a human trophoblast-like choriocarcinoma cell line, using immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). When BeWo cells were cultured with anti-CD9 monoclonal antibodies (mAb), their invasion through the extracellular matrices was significantly enhanced in a dose-dependent manner. Cell proliferation and human chorionic gonadotrophin production were unaffected. On the other hand, culture in the presence of mAb against integrins alpha3, alpha5 and beta1, which partially block the interaction with the extracellular matrices, inhibited BeWo cell invasion. Anti-CD9 monoclonal antibody had a stimulatory effect on BeWo cell invasion in the presence of anti-integrin alpha3 antibody. In contrast, it had no effect in the presence of mAb against integrins alpha5 and beta1, which were also highly expressed on BeWo cells. These findings suggest that CD9 has a function connected with the invasive properties of BeWo cells, which is partially mediated by integrin alpha5beta1. This may relate to the involvement of CD9 in trophoblastic invasion. (+info)
Genetic mapping of a maternal locus responsible for familial hydatidiform moles.
Hydatidiform mole (HM) is the product of an aberrant human pregnancy in which there is an abnormal embryonic development and proliferation of placental villi. The incidence of HM varies between ethnic groups, and occurs in 1 in every 1500 pregnancies in the USA. All HM cases are sporadic, except for extremely rare familial cases. The exact mechanisms leading to molar pregnancies are unknown. We previously postulated that women with recurrent hydatidiform moles are homozygous for an autosomal recessive defective gene. To map this gene genetically, we initiated a genome-wide scan with highly polymorphic short tandem repeats in individuals from two families with recurrent HM. Here, we demonstrate that a defective maternal gene is responsible for recurrent HM. This gene resides on chromosome 19q13.3-13.4 in a 15.2 cM interval flanked by D19S924 and D19S890. The identification of a gene for HM adds new insights into the molecular genetics of early embryogenesis and may be relevant to the large number of patients with sporadic HM. (+info)
Ubiquitous induction of p53 in tumor cells by antisense inhibition of MDM2 expression.
BACKGROUND: The MDM2 oncogene functions as a negative feedback regulator of the p53 tumor suppressor. Abnormal expression of MDM2 in tumors may attenuate the p53-mediated growth arrest and apoptosis response, resulting in increased cell proliferation and resistance to chemotherapy. MATERIALS AND METHODS: We have developed phosphorothioate antisense oligodeoxynucleotides optimized for inhibition of MDM2 expression and investigated the role of MDM2 in a large panel of tumor cell lines. RESULTS: Inhibition of MDM2 expression in 15 tumor types containing wild-type p53 results in a significant induction of nuclear p53 accumulation. The increase in p53 level is due to prolonged half-life and is associated with an increase in p53 transcriptional activity, growth inhibition, or apoptosis. Inhibition of MDM2 expression is also sufficient to induce nuclear p53 accumulation in several cell lines with cytoplasmic p53. CONCLUSIONS: The MDM2 negative feedback loop is important for maintenance of p53 at a low level by promoting p53 degradation. Nuclear export and degradation by MDM2 may contribute to the p53 nuclear exclusion phenotype. Inhibition of MDM2 expression can effectively activate p53 in most tumor types, including those without MDM2 overexpression, and may have broad anti-tumor potential. (+info)