568,133 research outputs found
Peritoneal ectopic lesions from women with endometriosis show abnormalities in progesterone-dependent glycan expression.
Examination of 12 paired peritoneal ectopic and eutopic endometria for histochemical binding of Dolichos biflorus agglutinin, normally found in the mid–late secretory part of the cycle, showed a failure of lectin binding in 9 of 11 secretory-phase lesions although the eutopic specimens generally stained normally. This failure of glycan expression in the secretory phase may result from various anomalies, including an inability to respond to progesterone, possibly due to a lack of, or to nonfunctional, progesterone receptors, suggesting that an ectopic environment may produce changes in tissue cell biology and hormonal responsiveness compared with that of eutopic endometrium.
Our recent study (1) on the ultrastructure of ectopic lesions from a cohort of women with endometriosis showed many abnormalities, including indications of a failure to exhibit the normal process of differentiation in the secretory half of the cycle. This was manifested by an absence of glycogen deposition in basal vacuoles and of both giant mitochondria and nucleolar channel systems in the early–midsecretory phase of the cycle. There was also considerable heterogeneity in the morphology of the glands and cystic structures observed in the electron microscope. We have now investigated whether these ultrastructural changes are accompanied by a parallel failure to show biochemical differentiation, because we have also previously shown that normal endometrial tissue undergoes a progesterone-dependent biosynthesis of glycans bound by Dolichos biflorus lectin [2] and [3].
The study group originally comprised 26 women with visually and biopsy-proven endometriosis who had undergone laparoscopic excision of endometriotic deposits and endometrial curettage, as previously described (1); however, only 12 biopsies proved to contain glandular structures in the area of tissue selected for this part of the study. Menstrual cycles (28–30 days) were regular according to the history taken at the time of the outpatient appointment, and normal ovulatory pattern was confirmed by day 21 serum progesterone. The stage of endometriosis at the time of laparoscopy was determined according to the revised American Society for Reproductive Medicine scoring system (4); all were red lesions. Eutopic tissue in each case was also taken, processed, and stained simultaneously with identical protocols
Ultrastructure of ectopic peritoneal lesions from women with endometriosis, including observations on the contribution of coelomic mesothelium.
Following a study in a baboon model of endometriosis, we here describe the morphology of ectopic peritoneal lesions in the human to examine the effects of an ectopic site on glandular structure and function. Ectopic biopsies from 17 women with endometriosis were fixed and processed for electron microscopy. Certain biopsies were also probed for intermediate filaments using immunohistochemistry. Ultrastructurally, lesions showed many different glandular morphologies with indications of delayed maturation compared to normal endometrium. Mesothelium covered some lesions and there was evidence of mesothelial invasion into the stroma. Ectopic endometriotic lesions from women with endometriosis showed ultrastructural differences from eutopic endometrium, with indications that mesothelial invasion may contribute to gland development in some lesions
RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss
Unexplained recurrent pregnancy loss (uRPL) is associated with repeated embryo loss and endometrial repair with elevated endometrial expression of inflammatory cytokines, including IFN-γ. Notch signaling through its transcription factor recombination signal binding protein Jκ (RBPJ) regulates mechanisms including the immune response and repair after tissue injury. Initially, null mutation of RBPJ in the mouse uterus ( Pgrcre/+Rbpjf/f; Rbpj c-KO) results in subfertility, but we have found that these mice become infertile after pregnancy as a result of dysfunctional postpartum uterine repair, including delayed endometrial epithelial and myometrial regeneration. RNA sequencing of postpartum uterine repair sites revealed global up-regulation of inflammatory pathways, including IFN signaling. Consistent with elevated IFN-γ, macrophages were recruited and polarized toward an M1-cytotoxic phenotype, which is associated with preventing repair and promoting further tissue injury. Through embryo transfer experiments, we show that dysfunctional postpartum repair directly impairs future embryo implantation in Rbpj c-KO mice. Last, we clinically correlated our findings from the Rbpj c-KO mouse in women diagnosed with uRPL. Reduced RBPJ in women with uRPL was associated with increased levels of IFN-γ. The data, taken together, indicate that RBPJ regulates inflammation during endometrial repair, which is essential for future pregnancy potential, and its dysregulation may serve as an unidentified contributor to uRPL in women.-Strug, M. R., Su, R.-W., Kim, T. H., Mauriello, A., Ticconi, C., Lessey, B. A., Young, S. L., Lim, J. M., Jeong, J.-W., Fazleabas, A. T. RBPJ mediates uterine repair in the mouse and is reduced in women with recurrent pregnancy loss
Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls--a pilot observational study.
Endometrial curettings from a cohort of 24 women with endometriosis were compared with matched biopsies from 14 healthy, fertile women and examined for ultrastructural changes and the secretion of glycans bound by the lectin from Dolichos biflorus. Ultrastructural analysis of glandular endometrial tissue from women with stages I to III endometriosis showed heterogeneous responses to the disease, biopsies often showing a mixture of features, combining delays in the maturation sequence with characteristics of later phenotypes particularly in the mid-late secretory phase of the menstrual cycle. Expression of glycans bound by Dolichos biflorus agglutinin was very variable in these cases but generally matched the observed ultrastructure. Biopsies from women with stage IV endometriosis showed immature gland morphology later in the cycle and also failed to express Dolichos biflorus agglutinin—binding glycans, suggesting an association between histological and biochemical function in advanced disease states. These findings may explain in part endometriosis-associated subfertility as blastocyst attachment is intimately associated with appropriate glycosylation and gland morphology
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Author Peter FitzSimons speaking at the National Library of Australia, Canberra, 13 November 2012 /
Title from acquisitions documentation.; Part of the collection: Portraits of author Peter FitzSimons speaking at the National Library of Australia, Canberra, 13 November 2012.; Acquired in digital format; access copy available online.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
Portrait of author David Foster at the National Library of Australia, Canberra, 8 June 2011 /
Title from acquisitions documentation.; Part of the collection: Portraits of author David Foster at the National Library of Australia, Canberra, 8 June 2011.; Acquired in digital format; access copy available online.; Mode of access: Online.; Photographed by a staff member of the National Library of Australia
Author-reader relationship at the site of the work
Within the format of a critical exegesis and four original works of extended prose fiction, this thesis explores the interaction between the author and reader and argues that literary meaning is the outcome of shifts of power between these two entities. It concludes that because these shifts in power are orchestrated by the author, the author is relevant to understanding how meaning is produced
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