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For skin gene therapy, achieving prolonged high-level gene expression in a significant percentage of keratinocytes (KC) is difficult because we cannot selectively target KC stem cells. We now demonstrate that topical colchicine treatment can be used to select, in vivo, KC progenitor cells transduced with the multidrug resistance gene (MDR1). When human skin(More)
Epidermis is renewed by a population of stem cells that have been defined in vivo by slow turnover, label retention, position in the epidermis, and enrichment in beta1 integrin, and in vitro by clonogenic growth, prolonged serial passage, and rapid adherence to extracellular matrix. The goal of this study is to determine whether clonogenic cells with(More)
Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic beta cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was(More)
Modulation of the kallikrein-kinin system (KKS) has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D). The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the(More)
The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the portal vein results in 10-15% hepatocyte transduction in vivo. This is(More)
Staphylococcus aureus is a major cause of surgical wound infections. The development of mechanisms of antimicrobial resistance by this and other bacterial pathogens has prompted the search for new approaches to treat infectious diseases. Hyaluronic acid binding peptides have been shown to modulate cellular trafficking during host responses and were assessed(More)
Tissue kallikrein (KLK-1), a serine protease, initiates the release of bradykinin (BK)-related peptides from low-molecular weight kininogen. KLK-1 and the BK B2 receptor (B2R) mediate beneficial effects on the progression of type 2 diabetes and renal disease, but the precise role of KLK-1 independent of its kinin-forming activity remains unclear. We used(More)
Highly metastatic mouse 10T1/2 cell lines (Ciras 2, Ciras 3 and dGC2M5) which have been T24-H-ras transfected, are shown to have differential responses in metastatic properties when grown in the presence of the processing inhibitors, swainsonine, castanospermine and deoxymannojirimycin. Concanavalin A binding data indicated the inhibitors caused similar(More)
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