1,118 research outputs found

    Estradiol, Progesterone, and Transforming Growth Factor Ξ± Regulate Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Expression in Mouse Endometrial Cells

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    Insulin-like growth factor 1 (IGF1) Is Involved in the proliferation of mouse and rat endometrial cells in a paracrine or autocrine manner. Insulin-like growth factor binding protein-3 (IGFBP3) modulates actions of IGFs directly or indirectly. The present study aimed to determine whether IGFBP3 is Involved In the regulation of proliferation of mouse endometrial cells. Mouse endometrial epithelial cells and stromal cells were isolated, and cultured In a serum free medium. IGF1 stimulated DNA synthesis by endometrial epithelial and stromal cells, and IGFBP3 Inhibited IGF1-induced DNA synthesis. Estradiol-17 beta (E2) decreased the Igfbp3 mRNA level in endometrial stromal cells, whereas It Increased the Igf1 mRNA level. Transforming growth factor alpha (TGF alpha) significantly decreased IGFBP3 expression at both the mRNA and secreted protein levels in endometrial stromal cells. Progesterone (134) did not affect the E2-induced down-regulation of Igfbp3 mRNA expression in endometrial stromal cells, although P4 alone increased Igfbp3 mRNA levels. The present findings suggest that in mouse endometrial stromal cells E2 enhances IGF1 action through enhancement of IGF1 synthesis and reduction of IGFBP3 synthesis, and that TGF alpha affects IGF1 actions through modulation of IGFBP3 levels

    Time-Reversal Symmetry-Breaking Superconductivity in Heavy Fermion PrOs4Sb12 detected by Muon Spin Relaxation

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    We report on muon spin relaxation measurements of the 4f^2-based heavy-fermion superconductor filled-skutterudite PrOs4Sb12. The results reveal the spontaneous appearance of static internal magnetic fields below the superconducting transition temperature, providing unambiguous evidence for the breaking of time-reversal symmetry in the superconducting state. A discussion is made on which of the spin or orbital component of Cooper pairs carries a nonzero momentum.Comment: 5 pages with 3 figure

    Troubled social background of male anabolic-androgenic steroid abusers in treatment

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the social background and current social situation of male abusers of anabolic-androgenic steroids (AAS).</p> <p>Methods</p> <p>We compared thirty-four AAS-abusing patients from an Addiction Centre (AC) with two groups, 18 users and 259 non-users of AAS from a public gym in Orebro, Sweden. The study is based on semi-structured interviews and questionnaires.</p> <p>Results</p> <p>Histories of a troubled childhood as well as current social disadvantage were both more frequent among the AAS users. Users also reported poor relationships with their parents and almost half of them had experienced physical or mental abuse. The AC group's experiences from school were mostly negative, and included concentration problems, boredom and learning difficulties. Their current circumstance included abuse of other drugs, battering of spouses and other criminality such as assault, illegal possession of weapons and theft.</p> <p>Conclusion</p> <p>In conclusion, this study shows that abusers of AAS often have a troubled social background. This underlines the importance of making a thorough social assessment as a part of the treatment programme. The results of the study may help in directing appropriate questions relevant to the abuse of AAS.</p

    Phase III Trial of Everolimus in Metastatic Renal Cell Carcinoma: Subgroup Analysis of Japanese Patients from RECORD-1

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    Objective: To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma. Methods: A subgroup analysis of the pivotal Phase III, randomized, double-blind, placebocontrolled trial of everolimus 10 mg/day in patients with disease progression after treatment with sorafenib, sunitinib or both assessed outcomes in Japanese participants. Results were compared with those for the overall study population. Results: The final trial analysis included 24 Japanese patients (everolimus, n 15; placebo, n 9). Median progression-free survival in the Japanese subpopulation was 5.75 months (95% confidence interval, 4.90 months to not reached) with everolimus and 3.61 months (95 % confidence interval, 1.91–9.03 months) with placebo (hazard ratio, 0.19; 95 % confidence interval, 0.05–0.83). Median overall survival was not reached with everolimus and was 14.9 month

    Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth

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    Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity
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