Publications by authors named "James K Pretorius"
Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in the Fab region to promote efficient and stable cognate light-heavy chain pairing.
View Article and Find Full Text PDFObjective: Sclerostin plays a major role in regulating skeletal bone mass, but its effects in articular cartilage are not known. The purpose of this study was to determine whether genetic loss or pharmacologic inhibition of sclerostin has an impact on knee joint articular cartilage.
Methods: Expression of sclerostin was determined in articular cartilage and bone tissue obtained from mice, rats, and human subjects, including patients with knee osteoarthritis (OA).
Article Synopsis
- - Calcimimetics enhance the activity of the calcium-sensing receptor (CaSR), which lowers parathyroid hormone (PTH) levels, raises calcitonin secretion, and reduces serum calcium levels, making them useful in treating patients with secondary hyperparathyroidism related to chronic kidney disease.
- - Cinacalcet is a second-generation calcimimetic, but researchers have developed a third-generation calcimimetic aimed at effectively lowering PTH without causing low calcium levels (hypocalcemia) or increasing calcitonin secretion in early renal disease patients.
- - The new compound showed promising results in experimental models by successfully reducing PTH levels and demonstrating lower effectiveness in stimulating calcitonin release compared to earlier calcim
A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis.
Int J Radiat Oncol Biol Phys
September 2006
Purpose: To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients.
Methods And Materials: A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg).