Erythropoietin stimulates proliferation of human renal carcinoma cells

Erythropoietin stimulates proliferation of human renal carcinoma cells.BackgroundWe reported recently that normal human, rat, and mouse tubular cells express authentic erythropoietin-receptors (EPO-R) through which EPO stimulates mitogenesis. The present study examines whether EPO could elicit such a proliferative and thereby potentially detrimental response in cells of human renal-cell carcinoma (RCC).MethodsNephrectomy samples were screened from patients with RCC (one chromophilic, two clear cell) as well as cell lines of human (Caki-2, 786-0) and mouse (RAG) renal adenocarcinomas for expression of EPO-R transcripts and protein. Cells were further tested for specific 125I-EPO binding and mitogenic response to EPO.ResultsAuthentic EPO-R transcripts and protein (approximately 72 kD) were detected in renal tumors and cell lines. Tumors showed low-level EPO expression, while cell lines did not. In cells, specific 125I-EPO binding to a single class of EPO-R (apparent Kd 1.3 to 1.4 nmol/L, Bmax 2.2 to 2.6 fmol/mg protein) was observed. EPO stimulated cell proliferation dose dependently, and the individual mitogenic effects of either EPO or 10% newborn calf serum were markedly amplified when both were coadministered.ConclusionThese data are the first to demonstrate, to our knowledge, that human RCCs express EPO-R message and protein and that receptor activation stimulates their proliferation in vitro. If these mitogenic effects of EPO are also operative in patients with RCC, endogenous EPO or its administration for the treatment of anemia could potentially hasten proliferation of renocellular malignancies

Human, rat, and mouse kidney cells express functional erythropoietin receptors

Cells of human, rat, and mouse kidney express functional erythropoietin receptors.BackgroundErythropoietin (EPO), secreted by fibroblast-like cells in the renal interstitium, controls erythropoiesis by regulating the survival, proliferation, and differentiation of erythroid progenitor cells. We examined whether renal cells that are exposed to EPO express EPO receptors (EPO-R) through which analogous cytokine responses might be elicited.MethodsNormal human and rat kidney tissue and defined cell lines of human, rat, and mouse kidney were screened, using reverse transcription-polymerase chain reaction, nucleotide sequencing, ligand binding, and Western blotting, for the expression of EPO-R. EPO's effects on DNA synthesis and cell proliferation were also examined.ResultsEPO-R transcripts were readily detected in cortex, medulla, and papilla of human and rat kidney, in mesangial (human, rat), proximal tubular (human, mouse), and medullary collecting duct cells (human). Nucleotide sequences of EPO-R cDNAs from renal cells were identical to those of erythroid precursor cells. Specific 125I-EPO binding revealed a single class of high- to intermediate-affinity EPO-Rs in each tested cell line (kD 96 pM to 1.4 nM; Bmax 0.3 to 7.0 fmol/mg protein). Western blots of murine proximal tubular cell membranes revealed an EPO-R protein of approximately 68 kDa. EPO stimulated DNA synthesis and cell proliferation dose dependently.ConclusionThis is the first direct demonstration, to our knowledge, that renal cells possess EPO-Rs through which EPO stimulates mitogenesis. This suggests currently unrecognized cytokine functions for EPO in the kidney, which may prove beneficial in the repair of an injured kidney while being potentially detrimental in renal malignancies

BMI Change, Fitness Change and Cardiometabolic Risk Factors among 8 th Grade Youth

This paper examined whether a two-year change in fitness, body mass index (BMI) or the additive effect of change in fitness and BMI were associated with change in cardiometabolic risk factors among youth. Cardiometabolic risk factors, BMI group (normal weight, overweight or obese) were obtained from participants at the start of 6th grade and end of 8th grade. Shuttle run laps were assessed and categorized in quintiles at both time points. Regression models were used to examine whether changes in obesity, fitness or the additive effect of change in BMI and fitness were associated with change in risk factors. There was strong evidence (p < .001) that change in BMI was associated with change in cardiometabolic risk factors. There was weaker evidence of a fitness effect, with some evidence that change in fitness was associated with change in total cholesterol, HDL-C, LDL-C and clustered risk score among boys, as well as HDL-C among girls. Male HDL-C was the only model for which there was some evidence of a BMI, fitness and additive BMI*fitness effect. Changing body mass is central to the reduction of youth cardiometabolic risk. Fitness effects were negligible once change in body mass had been taken into account

Validity of self-reported leisure-time sedentary behavior in adolescents

<p>Abstract</p> <p>Background</p> <p>To evaluate the concordance between leisure-time sedentary behavior in adolescents assessed by an activity-based questionnaire and accelerometry.</p> <p>A convenience sample of 128 girls and 73 boys, 11-15 years of age (12.6 ± 1.1 years) from six states across the United States examined as part of the feasibility studies for the Trial of Activity in Adolescent Girls (TAAG). Three days of self-reported time spent watching TV/videos, using computers, playing video/computer games, and talking on the phone was assessed using a modified version of the Self-Administered Physical Activity Checklist (SAPAC). Criterion measure of sedentary behavior was via accelerometry over three days using a cut point of < 50 counts · 30 sec^-1epoch. Comparisons between sedentary behavior by the two instruments were made.</p> <p>Results</p> <p>Adolescents generally underestimated minutes of sedentary behavior compared to accelerometry-measured minutes. The overall correlation between minutes of sedentary behavior by self-report and accelerometry was weak (Spearman r = 0.14; 95% CI 0.05, 0.23). Adjustment of sedentary minutes of behavior for total minutes assessed using either percentages or the residuals method tended to increase correlations slightly. However, regression analyses showed no significant association between self-reported sedentary behavior and minutes of sedentary behavior captured via accelerometry.</p> <p>Discussion</p> <p>These findings suggest that the modified 3-day Self-Administered Physical Activity Checklist is not a reliable method for assessing sedentary behavior. It is recommended that until validation studies for self-report instruments of sedentary behavior demonstrate validity, objective measures should be used.</p

The serious games ecosystem: Interdisciplinary and intercontextual praxis

This chapter will situate academia in relation to serious games commercial production and contextual adoption, and vice-versa. As a researcher it is critical to recognize that academic research of serious games does not occur in a vaccum. Direct partnerships between universities and commercial organizations are increasingly common, as well as between research institutes and the contexts that their serious games are deployed in. Commercial production of serious games and their increased adoption in non-commercial contexts will influence academic research through emerging impact pathways and funding opportunities. Adding further complexity is the emergence of commercial organizations that undertake their own research, and research institutes that have inhouse commercial arms. To conclude, we explore how these issues affect the individual researcher, and offer considerations for future academic and industry serious games projects