Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer

Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium.

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer

Dissociation in borderline personality disorder: recent experimental, neurobiological studies, and implications for future research and treatment

Stress and Psychopatholog

Linking experiences of child sexual abuse to adult sexual intimate partner violence: the role of borderline personality features, maladaptive cognitive emotion regulation, and dissociation

Stress and Psychopatholog

Histopathological characterization of experimentally induced cutaneous loxoscelism in rabbits inoculated with Loxosceles similis venom

Envenomation by Loxosceles bites is characterized by dermonecrotic and/or systemic features that lead to several clinical signs and symptoms called loxoscelism. Dermonecrotic lesions are preceded by thrombosis of the dermal plexus. Recent studies show that atheromatous plaque is prone to thrombosis due to endothelial cell apoptosis. To the best of our knowledge, there are no reports of microscopic dermal lesion and endothelial cell apoptosis induced by Loxosceles similis venom in the literature. Thus, the aim of the present study is to describe histological lesions induced by L. similis venom in rabbit skin and to elucidate whether apoptosis of endothelial cells is involved in the pathogenesis of loxoscelism. Forty male rabbits were split into two groups: the control group (intradermally injected with 50 µL of PBS) and the experimental group (intradermally injected with 0.5 µg of L. similis crude venom diluted in 50 µL of PBS). After 2, 4, 6 and 8 hours of injection, skin fragments were collected and processed for paraffin or methacrylate embedding. Sections of 5 µm thick were stained by HE, PAS or submitted to TUNEL reaction. Microscopically, severe edema, diffuse heterophilic inflammatory infiltrate, perivascular heterophilic infiltrate, thrombosis, fibrinoid necrosis of arteriolar wall and cutaneous muscle necrosis were observed. Two hours after venom injection, endothelial cells with apoptosis morphology were evidenced in the dermal plexus. Apoptosis was confirmed by TUNEL reaction. It seems that endothelial cell apoptosis and its consequent desquamation is an important factor that induces thrombosis and culminates in dermonecrosis, which is characteristic of cutaneous loxoscelism

CRF receptor antagonists: Utility in research and clinical practice

CRF, CRF-relatcd peptides and CRF receptors constitute a complex physiological system which has a key role in facilitating the adaptation of the organism to the stressful stimuli of the environment. The behavioral, endocrine. autonomic and immune branches or stress response are considered to be under the coordinating effects of CRF and its related peptides. The effects of these peptides are mediated through two distinct receptors, types 1 and 2 CRF receptors (CRF, and CRF2). The two receptors are encoded by separate genes and belong to the G-coupled receptor superfamily. The wide influence of the CRF system on physiological processes in both brain and periphery, suggests the implication of the respective peptides in the pathophysiology of numerous disorders which involve dysregulated stress responses. The potential use of CRF antagonists in such disorders is currently under intense investigation. Furthermore, such compounds have been invaluable in elucidating the physiology of the CRF system. This review will focus on existing data on the structural and pharmacological characteristics as well as the experimental and potential clinical uses of non-peptide, small molecule CRF antagonists

Regulation of endometrial cancer cell growth by luteinising hormone (LH) and follicle stimulating hormone (FSH)

Gonadotrophin releasing hormone analogues (GnRHa) have been used to treat recurrent endometrial cancer. However, the mode of action is uncertain. Our previous studies showed no direct effect of GnRHa on endometrial cancer cell growth in vitro. We have now examined the effect of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on endometrial cancer cell growth. The aim was to determine whether suppression of pituitary LH and FSH by GnRHa could explain the tumour regression seen in up to 44% of patients treated with this drug. We show that recombinant human LH and FSH (rhLH and rhFSH) produce a concentration dependent stimulation of the endometrial cancer cell line HEC-1A, in serum-free medium (maximum increase of 62 and 50% respectively relative to untreated controls). This increase is equivalent to that obtained by addition of 10% newborn calf serum. Growth of the Ishikawa cell line in culture increases in the presence of rhLH (maximum increase of 67%) but not with rhFSH. Using RT-PCR, we show that the Ishikawa cell line intermittently expresses receptor mRNA of LH but not of FSH; there is no expression of either mRNA by HEC-1A. Classically, both LH and FSH act via cAMP linked membrane receptors. However, neither rhLH nor rhFSH elicit cAMP production in either of our endometrial cancer cell lines. Thus, although a growth response to LH and FSH can be shown, and some cells express the LH receptor, stimulation appears to be via a pathway separate from that of the classical gonadotrophin receptor

Peeking through the trapdoor: Historical biogeography of the Aegean endemic spider Cyrtocarenum Ausserer, 1871 with an estimation of mtDNA substitution rates for Mygalomorphae

The Aegean region, located in the Eastern Mediterranean, is an area of rich biodiversity and endemism. Its position, geographical configuration and complex geological history have shaped the diversification history of many animal taxa. Mygalomorph spiders have drawn the attention of researchers, as excellent model systems for phylogeographical investigations. However, phylogeographic studies of spiders in the Aegean region are scarce. In this study, we focused on the phylogeography of the endemic ctenizid trap-door spider Cyrtocarenum Ausserer, 1871. The genus includes two morphologically described species: C. grajum (C.L. Koch, 1836) and C. cunicularium (Olivier, 1811). We sampled 60 specimens from the distributions of both species and analyzed four mitochondrial and two nuclear markers. Cyrtocarenum served as an example to demonstrate the importance of natural history traits in the inference of phylogeographic scenarios. The mtDNA substitution rates inferred for the genus are profoundly higher compared to araneomorph spiders and other arthropods, which seems tightly associated with their biology. We evaluate published mtDNA substitution rates followed in the literature for mygalomorph spiders and discuss potential pitfalls. Following gene tree (maximum likelihood, Bayesian inference) and species tree approaches (*BEAST), we reconstructed a time-calibrated phylogeny of the genus. These results, combined with a biogeographical ancestral-area analysis, helped build a biogeographic scenario that describes how the major palaeogeographic and palaeoclimatic events of the Aegean may have affected the distribution of Cyrtocarenum lineages. The diversification of the genus seems to have begun in the Middle Miocene in the present west Aegean area, while major phylogenetic events occurred at the Miocene-Pliocene boundary for C. cunicularium, probably related to the Messinian Salinity Crisis. Our results also demonstrate the clear molecular distinction of the two morphologically described species, but possible cryptic lineages may exist within C. cunicularium. © 2016 Elsevier Inc