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Enhanced Risk (enhanced + risk)
Selected Abstracts15-Deoxy ,12,14 -prostaglandin J2 suppresses transcription by promoter 3 of the human thromboxane A2 receptor gene through peroxisome proliferator-activated receptor , in human erythroleukemia cellsFEBS JOURNAL, Issue 18 2005Adrian T. Coyle In humans, thromboxane (TX) A2 signals through two receptor isoforms, thromboxane receptor (TP), and TP,, which are transcriptionally regulated by distinct promoters, Prm1 and Prm3, respectively, within the single TP gene. The aim of the current study was to investigate the ability of the endogenous peroxisome proliferator-activated receptor (PPAR), ligand 15-deoxy-,12,14 -prostaglandin J2 (15d-PGJ2) to regulate expression of the human TP gene and to ascertain its potential effects on the individual TP, and TP, isoforms. 15d-PGJ2 suppressed Prm3 transcriptional activity and TP, mRNA expression in the platelet progenitor megakaryocytic human erythroleukemia (HEL) 92.1.7 cell line but had no effect on Prm1 or Prm2 activity or on TP, mRNA expression. 15d-PGJ2 also resulted in reductions in the overall level of TP protein expression and TP-mediated intracellular calcium mobilization in HEL cells. 15d-PGJ2 suppression of Prm3 transcriptional activity and TP, mRNA expression was found to occur through a novel mechanism involving direct binding of PPAR,,retinoic acid X receptor (RXR) heterodimers to a PPAR, response element (PPRE) composed of two imperfect hexameric direct repeat (DR) sequences centred at ,159 and ,148, respectively, spaced by five nucleotides (DR5). These data provide direct evidence for the role of PPAR, in the regulation of human TP gene expression within the vasculature and point to further critical differences in the modes of transcriptional regulation of TP, and TP, in humans. Moreover, these data highlight a further link between enhanced risk of cardiovascular disease in diabetes mellitus associated with increased synthesis and action of thromboxane A2 (TXA2). [source] Expression of estrogen receptor alpha increases leptin-induced STAT3 activity in breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Nadine A. Binai Abstract Adipositas correlates with an enhanced risk of developing malignant diseases such as breast cancer, endometrial tumor or prostate carcinoma, but the molecular basis for this is not well understood. Potential mechanisms include increased bioavailability of adipocytokines (e.g. leptin) and steroid hormones. Here, we investigated cross-talk between ER, (estrogen receptor alpha) and leptin-induced activation of signal transducer and activator of transcription 3 (STAT3), a transactivator of important oncogenes. Upon leptin binding to its receptor Ob-RL (obesity receptor), STAT3 tyrosine phosphorylation and transactivation activity were enhanced by simultaneously expressing ER,. Downregulation of ER, using small interfering RNA abolished leptin-induced STAT3 phosphorylation. Interestingly, leptin-mediated STAT3 activation was unaffected by co-stimulation with the ER, ligands estradiol (E2) or estrogen antagonists ICI182,780 and tamoxifen, implying that enhancement of leptin-mediated STAT3 activity is independent of ER, ligands. We also detected ER, binding to STAT3 and JAK2 (Janus kinase 2), resulting in enhanced JAK2 activity upstream of STAT3 in response to leptin that might lead to an increased ER,-dependent cell viability. Altogether, our results indicate that leptin-induced STAT3 activation acts as a key event in ER,-dependent development of malignant diseases. [source] Extent of peri-implantitis-associated bone lossJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2009Christer Fransson Abstract Objective: The purpose of the present study was to describe the extent of peri-implantitis-associated bone loss with regard to implant position. Material and methods: Patient files and intra-oral radiographs from 182 subjects were analysed. Among the 1070 examined implants, 419 exhibited peri-implantitis-associated bone loss. The position of each implant within the jaw and fixed reconstructions was determined. In the radiographs the distance between the abutment-fixture junction and the most coronal position of bone to implant contact was assessed at the 419 "affected" implants using a magnifying lens (× 7) with a 0.1 mm graded scale. Results: About 40% of the implants in each subject was affected by peri-implantitis-associated bone loss. The proportion of such implants varied between 30% and 52% in different jaw positions and the most common position was the lower front region. In addition, affected implants were found in larger proportions among "mid" than "end" abutments irrespective of supporting fixed complete or fixed partial dentures. Conclusion: It is suggested that peri-implantitis occurs in all jaw positions and that an "end"-abutment position in a fixed reconstruction is not associated with an enhanced risk for peri-implantitis. [source] Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009N. RAHE-MEYER Background: Platelet dysfunction contributes to the pathophysiology of bleeding complications during and after cardiac surgery. In most surgical institutions, no peri-operative point-of-care monitoring of platelet function is used. We evaluated the usefulness of the Multiplate® platelet function analyser based on impedance aggregometry for identifying groups of patients at a high risk of transfusion of platelet concentrates (PC). Methods: Platelet function parameters were determined in 60 patients before and after routine cardiac surgery. Impedance aggregometry measurements were performed on Multiplate® using ADP (ADPtest), collagen (COLtest) and thrombin receptor activating peptide (TRAPtest) as platelet activators. The correlations between the aggregometry results and the transfusion of PC were calculated. The results of the aggregation tests were also divided into tertiles and the differences in PC transfusion between the low and the high tertile were assessed. Results: Low aggregometry delimited groups of patients with significantly higher PC transfusion. In the receiver operating characteristic curve, low pre-operative aggregation in the ADPtest identified patients with high total transfusion of PC (area under the curve 0.74, P=0.001), while the ADPtest performed at the end of the operation identified patients with high PC transfusion on the intensive care unit (ICU) (area under the curve 0.76, P=0.002). Conclusions: Near-patient platelet aggregation may allow the identification of patients with enhanced risk of PC transfusion, both pre-operatively and upon arrival on the ICU. [source] Radiation and breast carcinogenesis,PEDIATRIC BLOOD & CANCER, Issue 5 2001John D. Boice Jr. Abstract With the possible exception of radiation-induced leukemia, more is known about radiation-induced breast cancer than any other malignancy [1, 2]. Fourteen cohort studies have provided quantitative information on the level of risk following a wide range of doses in different populations around the world. Comprehensive studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic countries, the United Kingdom, and the USA (Table I). Key features are the linearity in the dose response (i.e., a straight line adequately fits the observed data), and the effect modification of age at exposure (i.e., risk is inversely related to exposure age and exposures past the menopausal ages appear to carry a very low risk); and the minimal effect of fractionating dose on subsequent risk [3]. A recent combined analysis of almost 78,000 women and 1,500 breast cancer cases from eight cohorts confirmed the downturn in risk at the highest dose levels (related in part to the killing of cells rather than transformation) and that fractionation of dose has little influence on risk, at least on an absolute scale [4]. It is not known whether persons predisposed to cancer are at enhanced risk of radiation-induced breast cancer from low-dose exposures, although this seems unlikely [5]. New data on the effects of high doses following childhood exposures will be forthcoming from long-term studies of the survivors of childhood cancer (6,8). Med. Pediatr. Oncol. 36:508,513, 2001. © 2001 Wiley-Liss, Inc. [source] | ||||||||||