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Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including(More)
Acute kidney injury occurs with kidney transplantation and too frequently progresses to the clinical diagnosis of delayed graft function (DGF). Poor kidney function in the first week of graft life is detrimental to the longevity of the allograft. Challenges to understand the root cause of DGF include several pathologic contributors derived from the donor(More)
Acute kidney dysfunction after ischemia-reperfusion injury (IRI) may be a consequence of persistent intrarenal vasoconstriction. Regulators of G-protein signaling (RGSs) are GTPase activators of heterotrimeric G proteins that can regulate vascular tone. RGS4 is expressed in vascular smooth muscle cells in the kidney; however, its protein levels are low in(More)
Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type(More)
BACKGROUND Gated single photon emission computed tomography (SPECT) provides information on myocardial perfusion and left ventricular ejection fraction (LVEF), which correlates with risk of cardiac events in patients with known or suspected coronary artery disease (CAD). We hypothesize that decreased LVEF at time of renal transplant evaluation is an(More)
Estimation of vitamin C (ascorbic acid) in various samples of fresh and frozen human plasma has shown that freezing in a regular freezer at -25 degrees C causes an approximately 14% loss of ascorbate in the sample. Freezing the same samples in a deep freezer at -75 degrees C causes less of an ascorbate loss amounting to about 9%. On the other hand, using(More)
Chronic kidney disease is often complicated by uremic cardiomyopathy that consists of left ventricular hypertrophy and interstitial fibrosis. It is thought that hypertension and volume overload are major causes of this disease, but here we sought to identify additional mechanisms using a mouse model of chronic renal insufficiency. Mice with a remnant kidney(More)
Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination(More)
Activation of the NMDA receptor complex increases the intracellular free Ca2+ concentration, which in turn influences a nitric oxide synthase (NOS) activity. In this study we investigated the NOS activity after acute and chronic electroconvulsive treatment in different rat brain regions. Chronic (10 daily treatments) but not acute (single treatment)(More)
Calcineurin inhibitors (CNI) are powerful immunomodulatory agents that produce marked renal dysfunction due in part to endothelin-1-mediated reductions in renal blood flow. Ligand-stimulated Gq protein signaling promotes the contraction of smooth muscle cells via phospholipase Cbeta-mediated stimulation of cytosolic calcium release. RGS4 is a GTPase(More)