Showing papers by "John C. S. Harding published in 2010"
TL;DR: Results indicate that dual heterologous PCV2a/2b inoculation 7 days apart may induce severe clinical illness, but PCV 2a and PCv2b when administered singularly or in combination with KLH appear to be of equivalent virulence.
45 citations
TL;DR: It is demonstrated that treatment of Tax+Arf-/- mice with zoledronic acid, a bisphosphonate inhibitor of OC activity and repressor of bone turnover, prevented or delayed the onset of OS, describing a novel role for ARF as a regulator of bone remodeling through effects on both OB and OC.
Abstract: The ARF tumor suppressor regulates p53 as well as basic developmental processes independent of p53, including osteoclast activation, by controlling ribosomal biogenesis. Here we provide evidence that ARF is a master regulator of bone remodeling and osteosarcoma (OS) development in mice. Arf(-/-) mice displayed increased osteoblast (OB) and osteoclast (OC) activity with a significant net increase in trabecular bone volume. The long bones of Arf(-/-) mice had increased expression of OB genes while Arf(-/-) OB showed enhanced differentiation in vitro. Mice transgenic for the Tax oncogene develop lymphocytic tumors with associated osteolytic lesions, while Tax+Arf(-/-) mice uniformly developed spontaneous OS by 7 months of age. Tax+Arf(-/-) tumors were well differentiated OS characterized by an abundance of new bone with OC recruitment, expressed OB markers and displayed intact levels of p53 mRNA and reduced Rb transcript levels. Cell lines established from OS recapitulated characteristics of the primary tumor, including the expression of mature OB markers and ability to form mineralized tumors when transplanted. Loss of heterozygosity in OS tumors arising in Tax+Arf(+/-) mice emphasized the necessity of ARF-loss in OS development. Hypothesizing that inhibition of ARF-regulated bone remodeling would repress development of OS, we demonstrated that treatment of Tax+Arf(-/-) mice with zoledronic acid, a bisphosphonate inhibitor of OC activity and repressor of bone turnover, prevented or delayed the onset of OS. These data describe a novel role for ARF as a regulator of bone remodeling through effects on both OB and OC. Finally, these data underscore the potential of targeting bone remodeling as adjuvant therapy or in patients with genetic predispositions to prevent the development of OS.
25 citations
18 Sep 2010
TL;DR: A syndrome in newly weaned pigs exhibiting anorexia followed by a catabolic series of events leading to body store depletion is explored and speculative reasoning that might be mechanistic in development is provided.
Abstract: In 2008 a presentation for the AD Leman Conference explored a syndrome in newly weaned pigs exhibiting anorexia followed by a catabolic series of events leading to body store depletion. Outcome was either death or euthanasia because of the serious debility of affected pigs. The authors chose the term “catabolic” as descriptive of the condition due to the mobilization of lipid stores, the loss of muscle mass, failure to grow and, eventually, fatty infiltration of liver and debilitation. This discussion described the syndrome, impact in an affected population and provided speculative reasoning that might be mechanistic in development.
6 citations