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Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3H-inositol phosphates in the presence of 10 mM Li+. Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC50 of 60 microM; stimulation was linear up to 60 min. This activation(More)
1 Genome-wide association studies have proven to be highly effective at defining relationships between single nucleotide poly-morphisms (SNPs) and clinical phenotypes in complex diseases. Establishing a mechanistic link between a noncoding SNP and the clinical outcome is a significant hurdle in translating associations into biological insight. We(More)
Insulin-like growth factor II (IGF-II) and mannose 6-phosphate (man-6-P) bind to distinct sites on the same receptor. In the present study, we examined the effects of man-6-P on the growth promoting effects of IGF-II on SH-SY5Y cultured human neuroblastoma cells. Man-6-P alone increased cell number and neurite outgrowth by approximately 50%; as previously(More)
The insulin-like growth factors (IGFs) are trophic factors whose growth-promoting actions are mediated via the IGF-I receptor and modulated by six IGF binding proteins (IGFBPs). In this study, we observed increased transcripts of both IGF-I and IGF-I receptor after rat sciatic nerve transection. Schwann cells (SCs) were the main source of IGF-I and IGFBP-5(More)
Benzodiazepines are in wide clinical use for their sedative and tranquilizing actions, the former being mediated via alpha1-containing GABAA receptors. The signal transduction pathways elicited beyond the receptor are only poorly understood. Changes of transcript levels in cerebral cortex induced by acute diazepam administration were therefore compared by(More)
Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks.(More)
Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD(+))(More)
PURPOSE This study examined the effects of peptides on inositol lipid turnover and intracellular calcium (Ca2+) levels in cultured human retinal pigment epithelium (RPE). METHODS Cultured human RPE were stimulated with bradykinin, arginine vasopressin (AVP), or bombesin. Accumulation of 3H-inositol phosphates in the presence of 10 mmol/l lithium reflected(More)
Podocytes are highly specialized epithelial cells with complex actin cytoskeletal architecture crucial for maintenance of the glomerular filtration barrier. The mammalian Rho GTPases Rac1 and Cdc42 are molecular switches that control many cellular processes, but are best known for their roles in the regulation of actin cytoskeleton dynamics. Here, we(More)
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