110 EXPRESSION AND CLONING OF OESTRADIOL RECEPTOR α AND PROGESTERONE RECEPTORS AND INTERFERONE STIMULATED GENE 15 IN ENDOMETRIUM AND CORPUS LUTEUM OF PREGNANT CAMEL

2011 ◽  
Vol 23 (1) ◽  
pp. 160
Author(s):  
A. S. Abdoon ◽  
O. M. Kandil ◽  
H. Kleim ◽  
D. Schams ◽  
B. Berisha ◽  
...  
Keyword(s):  
Western Blot ◽  
Corpus Luteum ◽  
Late Stage ◽  
Messenger Rna ◽  
Early Stage ◽  
Progesterone Receptors ◽  
Dromedary Camel ◽  
Dromedary Camels ◽  
Luteal Function ◽  
Breeding Animal

Despite their economic and cultural importance, dromedary camel is considered as a slow breeding animal, because of the higher incidence of early embryonic death. The present study was designed to investigate: 1) Expression and cloning of progesterone receptors (PR) and oestradiol receptor α (ERα) in CL and endometrium of pregnant camel; 2) Detection of interferon stimulated gene 15 (ISG15) in corpus luteum (CL) and endometrium of pregnant dromedary camels. For PR and ERα, RNA was extracted from CL and endometrium of dromedary camels during early (1 to 3 months), mid (4 to 9 months), and late stage (10 to 13 months) of pregnancy. Messenger RNA expression of PR and ERα was performed using RT-qPCR. Detection of ISG15 was performed using immunohistochemistry and Western blot analysis. In CL, both PR and ERα ± showed the same pattern with significantly high (P < 0.01) expression during early stage compared to mid or late stages of pregnancy. The lowest (P < 0.01) expression was detected during the late stage of pregnancy compared with the mid stage. There was no difference in mRNA expression for PR and ERα in endometrium of during the different stages of pregnancy in dromedary camels. ISG15 conjugated protein showed no expression in CL or endometrium of pregnant dromedary camels either by immunohistochemistry or Western blot. In conclusion, PR and ERα potentially play a role in regulating luteal function in CL during pregnancy in dromedary camels, further work is necessary to study the mechanism of pregnancy recognition in dromedary camels.

193 PROGESTERONE CONCENTRATIONS AND MESSENGER RNA EXPRESSION OF PROGESTERONE RECEPTORS IN ENDOMETRIAL TISSUE OF BOVINE UTERINE HORN IPSILATERAL AND CONTRALATERAL TO CORPUS LUTEUM

2015 ◽  
Vol 27 (1) ◽  
pp. 187
Author(s):  
H. Takahashi ◽  
S. Haneda ◽  
M. Matsui
Keyword(s):  
Progesterone Receptor ◽  
Mrna Expression ◽  
Corpus Luteum ◽  
Messenger Rna ◽  
Luteal Phase ◽  
Progesterone Receptors ◽  
Uterine Horn ◽  
Endometrial Tissue ◽  
Bovine Embryo ◽  
Oestrus Cycle

Generally, conception is established in the uterine horn ipsilateral to the corpus luteum (CL) in cattle. When a bovine embryo is transferred into the uterine horn contralateral to CL, conception rate is low. Since progesterone (P4) is essential for the establishment of pregnancy in cattle, locational effects of P4 released from CL at the uterus may cause the differences in fertility. The aim of this study was to determine the endometrial tissue P4 concentrations (EndP4) and the mRNA expression of nuclear progesterone receptor (PGR), and progesterone receptor component-1 (PGRMC-1) and -2 (PGRMC-2) in the endometrial tissues from the ipsi- and contralateral horn. The uteruses of Holstein cows were obtained at a local abattoir. Endometrial tissues were collected from both horns. Based on ovarian morphology, the oestrus cycle of the cow was estimated as follows: early luteal phase (ELP, Day 5–6, Day 0 = oestrus), mid luteal phase (MLP, Day 8–12), late luteal phase (LLP, Day 15–17), and follicular phase (FP, Day 18–20). EndP4 was measured by enzyme immunoassay. Expressions of mRNA were analysed by real-time RT–PCR. Two-way factorial ANOVA and the Steel-Dwass test were applied for a multiple comparison of means. The interrelations between both parameters were expressed by Spearman correlation coefficient. At ELP and MLP, EndP4 in ipsi-horn were higher than that in contra-horn (P < 0.05, see Table 1). Higher mRNA expression of PGRMC-1 in ipsi-horn was observed at ELP compared with contra-horn (P < 0.05). Expressions of mRNA for PGR and PGRMC-2 were similar in both horns. In ipsi-horn at ELP, EndP4 was positively correlated with PGRMC-1 mRNA (r = 0.87, P < 0.05), but was negatively correlated with PGR mRNA (r = –0.76, P < 0.05). However, in contra-horn, EndP4 has no correlation to mRNA expression of P4 receptors. In conclusion, EndP4 was influenced by the location of CL and stage of oestrus cycle. Higher expression of PGRMC-1 mRNA in endometrial tissue of ipsi-horn at ELP might be up-regulated by higher EndP4. These locational effects of CL on uterus may provide an intrauterine environment suitable for embryo development. Table 1.End P4 and expression of mRNA for P4 receptors in bovine uterine horn1

Endocrine changes, with emphasis on 13, 14–dihydro–15–keto–prostaglandin F2α and corticosteroids, before and during parturition in dromedary camels (Camelus dromedarius)

1994 ◽  
Vol 122 (2) ◽  
pp. 315-323 ◽  
Author(s):  
M. S. El-Belely
Keyword(s):  
Plasma Concentrations ◽  
Prostaglandin F2α ◽  
Dromedary Camel ◽  
Total Plasma ◽  
Dromedary Camels ◽  
Luteal Function ◽  
The Third ◽  
Tenfold Increase ◽  
Prostaglandin F ◽  
Consistent Increase

SUMMARYA study was conducted on eight preparturient camels which were kept in individual stalls adjacent to the Cairo abattoir during 1989. Four novel phenomena are described in this paper: (i) a significant (P < O·05) prepartum decrease in plasma concentrations of progesterone evident over the 48 h preceding parturition; (ii) a remarkably consistent increase in total plasma unconjugated oestrogens, commencing 2–4 days prior to parturition and peaking in excess of 200 pg/ml for c. 2 h before delivery; (iii) a tenfold increase to 5·4±0·19 ng/ml (mean±S.E.) in plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2α (PGFM) between days –10 and – 1, showing a sudden and large increase during the 5 h prior to delivery; and (iv) three peaks of total plasma corticosteroids during the 4 h preceding delivery, with the third peak showing the greatest magnitude (24·0±3·11 ng/ml). These results suggest that the dromedary camel is an example of a species in which luteal secretion of progesterone, especially 3α-dihydroprogesterone, is required throughout pregnancy and in which cessation of luteal function, associated with a rapid increase in the oestrogen: progesterone ratio and the secretion of prostaglandin F2α (PGF2α), is a requirement for parturition.

scholarly journals Impact of Autophagy Inhibition at Different Stages on Cytotoxic Effect of Autophagy Inducer in Glioblastoma Cells

2015 ◽  
Vol 35 (4) ◽  
pp. 1303-1316 ◽  
Author(s):  
Chenguang Li ◽  
Yaohua Liu ◽  
Huailei Liu ◽  
Weiguang Zhang ◽  
Chen Shen ◽  
...  
Keyword(s):  
Western Blot ◽  
Late Stage ◽  
Cytotoxic Effect ◽  
Apoptotic Cell ◽  
Early Stage ◽  
Initial Step ◽  
Beclin 1 ◽  
Therapeutic Effects ◽  
Glioblastoma Cells ◽  
Autophagy Inhibition

Background/Aims: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a poor prognosis. Combination treatment of autophagy inducer and autophagy inhibitor may be a feasible solution to improve the therapeutic effects. However, the correlation between them is unclear. The purpose of this study was to investigate the effect of autophagy inhibition at different stages on cytotoxicity of autophagy inducers in glioblastoma cells. Methods: Autophagy inhibition at early stage was achieved by 3-methyladenine (3-MA) or Beclin 1 shRNA. Autophagy inhibition at late stage was achieved by chloroquine (CQ) or Rab7 shRNA. Cell viability was assessed by MTT assay. Autophagy was measured using transmission electron microscopy and western blot. Apoptosis was measured using western blot and flow-cytometry. Results: Inhibition of early steps of autophagy by 3-MA or Beclin 1 knockdown decreased the toxic effect of arsenic trioxide (ATO) in GBM cell lines. In contrast, blockade of autophagy flux at late stage by CQ or Rab7 knockdown enhanced the cytotoxicity of ATO, and caused accumulation of degradative autophagic vacuoles and robust apoptosis. Moreover, depletion of Beclin 1 abolished the synergistic effect of ATO and CQ by reducing autophagy and apoptosis. Combination of CQ with other autophagy inducers also induced synergistic apoptotic cell death. Conclusion: These results suggest that inhibition of late process of autophagy, not initial step, increases the cytotoxic effect of autophagy inducers via autophagy and apoptosis, which may contribute to GBM chemotherapy.

scholarly journals Hypothyroidism prolongs corpus luteum function in the pregnant rat

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 197-205 ◽  
Author(s):  
María Belén Hapon ◽  
Alicia B Motta ◽  
Marcelo Ezquer ◽  
Melisa Bonafede ◽  
Graciela A Jahn
Keyword(s):  
Western Blot ◽  
Corpus Luteum ◽  
Blot Analysis ◽  
Inos Mrna ◽  
Rt Pcr ◽  
Pregnant Rat ◽  
Luteal Regression ◽  
Luteal Function ◽  
Prolonged Pregnancy ◽  
Stimulation Of

It has been shown that hypothyroidism in the rat produces a prolongation of pregnancy associated with a delay in the fall of circulating progesterone (P4) at term. The aim of the present work is to determine whether the delayed P4decline in hypothyroid mother rats is due to a retarded induction of P4degradation to 20αOH P4or to a stimulation of its synthesis, and to investigate the possible mechanisms that may underlie the altered luteal function. We determined by RIA the circulating profile of the hormones (TSH, PRL, LH, P4, PGF2α, and PGE2) involved in luteal regulation at the end of pregnancy and, by semiquantitative RT-PCR, the expression of factors involved in P4synthesis (CytP450scc, StAR, 3βHSD, PRLR) and metabolism (20αHSD, PGF2αR, iNOS and COX2). Our results show that the delay in P4decline and parturition is the resultant of retarded luteal regression, caused by a combination of decreases in luteolytic factors, mainly luteal PGF2α, iNOS mRNA expression and also circulating LH, and increased synthesis or action of luteotrophic factors, such as luteal and circulating PGE2 and circulating PRL. All these changes may be direct causes of the decreased 20αHSD mRNA and protein (measured by western blot analysis) expression, which in the presence of unchanged expression of the factors involved in P4synthesis results in elevated luteal and circulating P4that prolonged pregnancy and also may favor longer survival of the corpus luteum.

scholarly journals Expression and Regulation of Progestin Membrane Receptors in the Rat Corpus Luteum

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5522-5532 ◽  
Author(s):  
Zailong Cai ◽  
Carlos Stocco
Keyword(s):  
Corpus Luteum ◽  
Binding Proteins ◽  
Progesterone Receptors ◽  
Membrane Receptors ◽  
Luteal Cell ◽  
Membrane Component ◽  
Luteal Function ◽  
Protein Levels ◽  
Membrane Bound ◽  
Low Levels

Despite evidence strongly supporting progesterone’s autocrine actions in the rat corpus luteum (CL), classical progesterone receptors (PR) have not been detected in this gland. Alternatively, in several other systems, progestins have been reported to activate nongenomic pathways via putative progestin membrane receptors (PMRs). The aim of this investigation was to determine whether rat CL membranes bind progestins and contain PMR homologs and whether these proteins are expressed during CL development in a manner that parallels luteal function. We found that luteal cell membranes specifically bind progesterone. Low levels of progesterone and 20α-dihydroprogesterone decreased binding of [3H]progesterone, whereas androstenedione, 17α-hydroxyprogesterone, and pregnenolone were less potent. Other steroids, including corticosterone, mifepristone, and estradiol, were ineffective. We found that the rat CL expresses five genes previously postulated to encode for putative PMRs: PMRα, PMRβ, PMRγ, PR membrane component 1 (PRMC1), and Rda288. Pmrα, Pmrγ, and Prmc1 transcripts rose steadily during pregnancy whereas Pmrβ and Rda288 remained constant. Just before parturition, concomitant with falling progesterone levels, Pmrα, Pmrβ, and Prmc1 decreased. Luteal PMRα and PRMC1 protein levels were lower in samples taken at the end of pregnancy compared with midpregnancy samples. Ergocriptine, which inhibits the secretion of prolactin, the primary luteotrophic hormone in the rat CL, reduced Pmrα, Pmrβ, and Prmc1 expression significantly. Ergocriptine effects were prevented by coadministration of prolactin. These findings provide evidence for the expression and regulation of putative membrane-bound progestin-binding proteins in the rat CL, a tissue that does not express detectable levels of nuclear progesterone receptors.

The process of localizing a maternal messenger RNA in Xenopus oocytes

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 31-36
Author(s):  
Joel K. Yisraeli ◽  
Sergei Sokol ◽  
D. A. Melton
Keyword(s):  
Late Stage ◽  
Messenger Rna ◽  
Early Stage ◽  
Stage Iv ◽  
Microtubule Inhibitors ◽  
Maternal Mrna ◽  
Vegetal Cortex ◽  
Vegetal Pole ◽  
Cytoplasmic Microtubules

The maternal mRNA Vgl is localized to the vegetal pole during oogenesis in Xenopus. We have cultured oocytes in vitro to begin to understand how this localization occurs. Endogenous Vgl mRNA undergoes localization when oocytes are cultured in vitro, and synthetic Vgl mRNA injected into such oocytes is localized in the same fashion. Vgl mRNA is associated with a detergentinsoluble fraction from homogenized oocytes, suggesting a possible cytoskeletal association. The use of cytoskeletal inhibitors reveals a two-step process for localizing Vgl mRNA. Microtubule inhibitors such as nocodazole and colchicine inhibit the localization of Vgl mRNA in late stage III/early stage IV oocytes, but have no effect on Vgl mRNA once it is localized. The microfilament inhibitor cytochalasin B, however, has little effect on thetranslocation of Vgl mRNA in middle-stage oocytes but causes a release of the message in late-stage oocytes. We propose a model for the localization of Vgl mRNA in which translocation of the message to the vegetal cortex is achieved via cytoplasmic microtubules and the anchoring of the message at the cortex involves cortical microfilaments.

scholarly journals Making the Grade during Pandemic: Early-stage and Late-stage Provisional Institutions

2021 ◽  
pp. 073112142110286
Author(s):  
Alexander B. Kinney ◽  
Nicholas J. Rowland
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
State University ◽  
Institutional Work ◽  
Traditional Grading ◽  
Grading Policy ◽  
Temporary Solution ◽  
Rural State ◽  
Empirical Implications ◽  
Common Understanding

This is an article that draws on the institutional work literature about provisional institutions. To date, nearly every U.S. sector has been impacted by COVID-19. To sustain their core missions, highly institutionalized organizations such as universities have had to rethink foundational structures and policies. Using a historical ethnographic approach to investigate records from faculty senate deliberations at “Rural State University” (RSU), the authors examine the implementation of a temporary grading policy to supplement traditional, qualitative grades spring 2020 during the outbreak. The authors find that RSU implemented a temporary, supplemental grading policy as a provisional institution to momentarily supersede traditional grading as a means to—as soon as possible—return to it. This finding contrasts with the common understanding that provisional institutions operate primarily as a temporary solution to a social problem that leads to more stable and enduring, ostensibly nonprovisional institutions. The temporary grading policy, the authors argue, constitutes a “late-stage” provisional institution and, with this new lens, subsequently characterize the more commonplace understanding of provisional institutions as “early-stage.” This contribution has theoretical implications for studies of institutions and empirical implications for research on shared governance and disruption in higher education.

scholarly journals Age-Related Biology of Early-Stage Operable Breast Cancer and Its Impact on Clinical Outcome

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1417
Author(s):  
Binafsha M. Syed ◽  
Andrew R. Green ◽  
Emad A. Rakha ◽  
David A.L. Morgan ◽  
Ian O. Ellis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Biological Characteristics ◽  
Cancer Specific Survival ◽  
Age Related ◽  
Significant Difference

As age advances, breast cancer (BC) tends to change its biological characteristics. This study aimed to explore the natural progression of such changes. The study included 2383 women with clinically T0-2N0-1M0 BC, managed by primary surgery and optimal adjuvant therapy in a dedicated BC facility. Tissue micro-arrays were constructed from their surgical specimens and indirect immunohistochemistry was used for analysis of a large panel (n = 16) of relevant biomarkers. There were significant changes in the pattern of expression of biomarkers related to luminal (oestrogen receptor (ER), progesterone receptors (PgR), human epidermal growth factor receptor (HER-2), E-cadherin, MUC1, bcl2 CK7/8, CK18 and bcl2) and basal (CK5/6, CK14, p53 and Ki67) phenotypes, lymph node stage, histological grade and pathological size when decade-wise comparison was made (p < 0.05). The ages of 40 years and 70 years appeared to be the milestones marking a change of the pattern. There were significantly higher metastasis free and breast cancer specific survival rates among older women with ER positive tumours while there was no significant difference in the ER negative group according to age. Biological characteristics of BC show a pattern of change with advancing age, where 40 years and 70 years appear as important milestones. The pattern suggests <40 years as the phase with aggressive phenotypes, >70 years as the less aggressive phase and 40–70 years being the transitional phase.

Health Insurance Status as a Predictor of Mode of Colon Cancer Detection but Not Stage at Diagnosis: Implications for Early Detection

2021 ◽  
pp. 003335492199917
Author(s):  
Lindsey A. Jones ◽  
Katherine C. Brewer ◽  
Leslie R. Carnahan ◽  
Jennifer A. Parsons ◽  
Blase N. Polite ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Health Insurance ◽  
Early Detection ◽  
Late Stage ◽  
Early Stage ◽  
Insurance Status ◽  
Stage At Diagnosis ◽  
Health Insurance Status ◽  
Percentage Point Increase ◽  
Point Increase

Objective For colon cancer patients, one goal of health insurance is to improve access to screening that leads to early detection, early-stage diagnosis, and polyp removal, all of which results in easier treatment and better outcomes. We examined associations among health insurance status, mode of detection (screen detection vs symptomatic presentation), and stage at diagnosis (early vs late) in a diverse sample of patients recently diagnosed with colon cancer from the Chicago metropolitan area. Methods Data came from the Colon Cancer Patterns of Care in Chicago study of racial and socioeconomic disparities in colon cancer screening, diagnosis, and care. We collected data from the medical records of non-Hispanic Black and non-Hispanic White patients aged ≥50 and diagnosed with colon cancer from October 2010 through January 2014 (N = 348). We used logistic regression with marginal standardization to model associations between health insurance status and study outcomes. Results After adjusting for age, race, sex, and socioeconomic status, being continuously insured 5 years before diagnosis and through diagnosis was associated with a 20 (95% CI, 8-33) percentage-point increase in prevalence of screen detection. Screen detection in turn was associated with a 15 (95% CI, 3-27) percentage-point increase in early-stage diagnosis; however, nearly half (47%; n = 54) of the 114 screen-detected patients were still diagnosed at late stage (stage 3 or 4). Health insurance status was not associated with earlier stage at diagnosis. Conclusions For health insurance to effectively shift stage at diagnosis, stronger associations are needed between health insurance and screening-related detection; between screening-related detection and early stage at diagnosis; or both. Findings also highlight the need to better understand factors contributing to late-stage colon cancer diagnosis despite screen detection.

scholarly journals EU FP7 research funding for an orphan drug (Orfadin®) and vaccine (Hep C) development: a success and a failure?

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
L. Schmidt ◽  
O. Sehic ◽  
C. Wild
Keyword(s):  
Hepatitis C ◽  
Late Stage ◽  
Research Funding ◽  
Early Stage ◽  
Basic Research ◽  
Pharmaceutical Products ◽  
Clinical Development ◽  
Clinical Indication ◽  
Market Authorisation ◽  
Risk Capital

Abstract Background We considered the extent of the contribution of publicly funded research to the late-stage clinical development of pharmaceuticals and medicinal products, based on the European Commission (EC) FP7 research funding programme. Using two EC FP7-HEALTH case study examples—representing two types of outcomes—we then estimated wider public and charitable research funding contributions. Methods Using the publicly available database of FP7-HEALTH funded projects, we identified awards relating to late-stage clinical development according to the systematic application of inclusion and exclusion criteria, classified them according to product type and clinical indication, and calculated total EC funding amounts. We then identified two case studies representing extreme outcomes: failure to proceed with the product (hepatitis C vaccine) and successful market authorisation (Orfadin® for alkaptonuria). Total public and philanthropic research funding contributions to these products were then estimated using publicly available information on funding. Results 12.3% (120/977) of all EC FP7-HEALTH awards related to the funding of late-stage clinical research, totalling € 686,871,399. Pharmaceutical products and vaccines together accounted for 84% of these late-stage clinical development research awards and 70% of its funding. The hepatitis C vaccine received total European Community (FP7 and its predecessor, EC Framework VI) funding of €13,183,813; total public and charitable research funding for this product development was estimated at € 77,060,102. The industry sponsor does not consider further development of this product viable; this now represents public risk investment. FP7 funding for the late-stage development of Orfadin® for alkaptonuria was so important that the trials it funded formed the basis for market authorisation, but it is not clear whether the price of the treatment (over €20,000 per patient per year) adequately reflects the substantial public funding contribution. Conclusions Public and charitable research funding plays an essential role, not just in early stage basic research, but also in the late-stage clinical development of products prior to market authorisation. In addition, it provides risk capital for failed products. Within this context, we consider further discussions about a public return on investment and its reflection in pricing policies and decisions justified.

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