MS 141 Guide to Frank Arnett, MD Papers, 1968-2010

The Frank Arnett, MD papers contains materials covering the professional career of Dr. Frank Arnett, MD. The collection includes medical objects, video, photographs of Dr. Arnett and colleagues, awards and recognitions, copies of presentation material, and grants awarded information. A large portion of the collection is composed of reprints of Dr. Arnett\u27s numerous publications, most on the genetics and genomics of multiple rheumatic diseases. See more at https://archives.library.tmc.edu/ms-141

Spatial Distribution of Nucleosynthesis Products in Cassiopeia A: Comparison Between Observations and 3D Explosion Models

We examine observed heavy element abundances in the Cassiopeia A supernova remnant as a constraint on the nature of the Cas A supernova. We compare bulk abundances from 1D and 3D explosion models and spatial distribution of elements in 3D models with those derived from X-ray observations. We also examine the cospatial production of 26Al with other species. We find that the most reliable indicator of the presence of 26Al in unmixed ejecta is a very low S/Si ratio (~0.05). Production of N in O/S/Si-rich regions is also indicative. The biologically important element P is produced at its highest abundance in the same regions. Proxies should be detectable in supernova ejecta with high spatial resolution multiwavelength observations.Comment: To appear in the Conference Proceedings for the "10th Symposium on Nuclei in the Cosmos (NIC X)", July 27 - August 1 2008, Mackinack Island, Michigan, US

Buschke-Ollendorff Syndrome Associated with Elevated Elastin Production by Affected Skin Fibroblasts in Culture

Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2–8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin flbroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-β1 (TGFβ1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGFβ1-stimulated elastin production, was able to reduce elastin production in basal and TGFβ1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis

Attenuation of fibrosis in vitro and in vivo with SPARC siRNA

INTRODUCTION: SPARC is a matricellular protein, which, along with other extracellular matrix components including collagens, is commonly over-expressed in fibrotic diseases. The purpose of this study was to examine whether inhibition of SPARC can regulate collagen expression in vitro and in vivo, and subsequently attenuate fibrotic stimulation by bleomycin in mouse skin and lungs. METHODS: In in vitro studies, skin fibroblasts obtained from a Tgfbr1 knock-in mouse (TBR1CA; Cre-ER) were transfected with SPARC siRNA. Gene and protein expressions of the Col1a2 and the Ctgf were examined by real-time RT-PCR and Western blotting, respectively. In in vivo studies, C57BL/6 mice were induced for skin and lung fibrosis by bleomycin and followed by SPARC siRNA treatment through subcutaneous injection and intratracheal instillation, respectively. The pathological changes of skin and lungs were assessed by hematoxylin and eosin and Masson\u27s trichrome stains. The expression changes of collagen in the tissues were assessed by real-time RT-PCR and non-crosslinked fibrillar collagen content assays. RESULTS: SPARC siRNA significantly reduced gene and protein expression of collagen type 1 in fibroblasts obtained from the TBR1CA; Cre-ER mouse that was induced for constitutively active TGF-beta receptor I. Skin and lung fibrosis induced by bleomycin was markedly reduced by treatment with SPARC siRNA. The anti-fibrotic effect of SPARC siRNA in vivo was accompanied by an inhibition of Ctgf expression in these same tissues. CONCLUSIONS: Specific inhibition of SPARC effectively reduced fibrotic changes in vitro and in vivo. SPARC inhibition may represent a potential therapeutic approach to fibrotic diseases