The physiological and clinical importance of sodium potassium ATPase in cardiovascular diseases

The Na/K-ATPase has been extensively studied, but it is only recently that its role as a scaffolding and signaling protein has been identified. It has been identified that cardiotonic steroids (CTS) such as digitalis mediate signal transduction through the Na/K-ATPase in a process found to result in the generation of reactive oxygen species (ROS). As these ROS also appear capable of initiating this signal cascade, a feed forward amplification process has been postulated and subsequently implicated in some disease pathways including uremic cardiomyopathy

Na/K-ATPase amplification of oxidant stress; a universal but unrecognized clinical target?

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating cardiotonic steroids setting the gain. Work in both cellular and animal models of disease suggest that this amplification process is activated in conditions characterized by oxidant stress ranging from cancer to obesity/metabolic syndrome and may serve as a potential clinical target for interventions

Education of Nurse Practitioners and Physician Assistants; What Role, if any, for Physicians in Determining Their Scope of Practice?

Recent changes in legislation allow for non-physicians to independently perform many of the duties previously restricted to physicians. There are potentially benefits to these changes, but the author is concerned that some of the attributes of physicians induced by the long and rigorous training embedded in the profession may be absent in this new, independent health-care work force

Effect of Removing Outliers on Statistical Inference: Implications to Interpretation of Experimental Data in Medical Research

Background Data editing with elimination of “outliers” is commonly performed in the biomedical sciences. The effects of this type of data editing could influence study results, and with the vast and expanding amount of research in medicine, this effect would be magnified. Methods and Results We first performed an anonymous survey of medical school faculty at institutions across the United States and found that indeed some form of outlier exclusion was performed by a large percentage of the respondents to the survey. We next performed Monte Carlo simulations of excluding high and low values from samplings from the same normal distribution. We found that removal of one pair of “outliers”, specifically removal of the high and low values of the two samplings, respectively had measurable effects on the type I error as the sample size was increased into the thousands. We developed an adjustment to the t score that accounts for the anticipated alteration of the type I error (tadj=tobs-2(log(n)^0.5/n^0.5)), and propose that this be used when outliers are eliminated prior to parametric analysis. Conclusion Data editing with elimination of outliers that includes removal of high and low values from two samples, respectively, can have significant effects on the occurrence of type 1 error. This type of data editing could have profound effects in high volume research fields, particularly in medicine, and we recommend an adjustment to the t score be used to reduce the potential for error

The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeuti

HST Observations and Models of The Gravitational Lens System MG 0414+0534

Quadruple gravitational lens systems offer the possibility of measuring time delays for image pairs, microlensing effects, and extinction in distant galaxies. Observations of these systems may be used to obtain estimates of H_o and to study the various mass components of lens galaxies at high redshifts. With HST, we have observed the reddest known gravitational lens system, MG 0414+0534. We used WFPC2/PC1 to obtain deep, high-resolution images with two filters, F675W and F814W. We present a detailed analysis of all of the components, as well as macrolens models. Our main results are: (1) confirmation that MG 0414+0534 is inescapably a gravitational lens system; (2) discovery of a blue arc connecting the 3 brightest images of the QSO central core; (3) accurate positions and apparent brightnesses for all 4 known images of the QSO central core and for the lens galaxy G; (4) a good representation of the brightness distribution of G by elliptical isophotes with a De Vaucouleurs profile, characteristic of an elliptical galaxy; (5) models that consist of simple elliptical potentials and account qualitatively, not quantitatively, for the HST image positions, arc morphology and radio flux ratios for the images of the QSO central core; (6) a possible new test to distinguish between reddening in the host galaxy of the QSO and in the lens galaxy, based on future accurate measurements of spatial variations in the color of the arc; and (7) the suggestion that microlensing is a plausible cause for the differences between the radio and optical flux ratios for the brightest images, A1 and A2. Further observations and measurements such as of the redshift of the lens galaxy, can be used fruitfully to study microlensing for this system.Comment: 27 pages, 8 .ps figs, AAS Latex, AJ, in press, Feb 199