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Microglia are crucial for immune responses in the brain. Although their origin from the yolk sac has been recognized for some time, their precise precursors and the transcription program that is used are not known. We found that mouse microglia were derived from primitive c-kit(+) erythromyeloid precursors that were detected in the yolk sac as early as 8 d(More)
Overexpression of Hairless (H) causes a remarkable degree of tissue loss and apoptosis during imaginal development. H functions as antagonist in the Notch-signaling pathway in Drosophila, and the link to growth and apoptosis is poorly understood. To further our insight into H-mediated apoptosis, we performed two large-scale screens for modifiers of a small(More)
Hypertension and kidney damage in the double transgenic rat (dTGR) harboring both human renin and human angiotensinogen genes are dependent on the human components of the renin angiotensin system. We tested the hypothesis that monocyte infiltration and increased adhesion molecule expression are involved in the pathogenesis of kidney damage in dTGR. We also(More)
We tested the hypothesis that the renin inhibitor aliskiren ameliorates organ damage in rats transgenic for human renin and angiotensinogen genes (double transgenic rat [dTGR]). Six-week-old dTGR were matched by albuminuria (2 mg per day) and divided into 5 groups. Untreated dTGR were compared with aliskiren (3 and 0.3 mg/kg per day)-treated and valsartan(More)
Aldosterone is implicated in cardiac hypertrophy and fibrosis. We tested the role of the mineralocorticoid receptor in a model of angiotensin II-induced cardiac injury. We administered spironolactone (SPIRO; 20 mg. kg(-1). d(-1)), valsartan (VAL; 10 mg. kg(-1). d(-1)), or vehicle to rats double transgenic for the human renin and angiotensinogen genes(More)
BACKGROUND The epithelial Ca(2+) channel (ECaC) exhibits the defining properties for being the gatekeeper in 1,25-dihydroxyvitamin D(3)-regulated Ca(2+) (re)absorption. Its recently cloned human orthologue (ECaC1) could, therefore, represent a crucial molecule in human disorders related to Ca(2+)-wasting such as idiopathic hypercalciuria (IH). METHODS(More)
The blood pressure-independent effects of angiotensin II (Ang II) were examined in double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes, in which the end-organ damage is due to the human components of the renin angiotensin system. Triple-drug therapy (hydralazine 80 mg/L, reserpine 5 mg/L, and hydrochlorothiazide 25 mg/L in(More)
Pre-eclampsia is a common, pregnancy-induced disorder, consisting of hypertension and proteinuria. The condition is one of the leading causes for maternal and perinatal morbidity and mortality. Nonetheless, the underlying molecular mechanisms remain unclear. Immunological mechanisms and the renin-angiotensin system have been implicated in the development of(More)
—Hypertension is linked to disturbed total-body sodium (Na ϩ) regulation; however, measuring Na ϩ disposition in the body is difficult. We implemented 23 Na magnetic resonance spectroscopy (23 Na-MR) and imaging technique (23 Na-MRI) at 9.4T for animals and 3T for humans to quantify Na ϩ content in skeletal muscle and skin. We compared 23 Na-MRI data with(More)
Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal(More)