@article{hill_ashwell_nolin_keeley_billingham_hinek_starcher_2007, title={Dietary iron deficiency compromises normal development of elastic fibers in the aorta and lungs of chicks}, volume={137}, ISSN={["1541-6100"]}, DOI={10.1093/jn/137.8.1895}, abstractNote={Elastic fibers play a key role in the structure and function of numerous organs that require elasticity. Elastogenesis is a complex process in which cells first produce a microfibrillar scaffold, composed of numerous structural proteins, upon which tropoelastin assembles to be cross-linked into polymeric elastin. Recently, it was demonstrated that low concentrations of free iron upregulate elastin gene expression in cultured fibroblasts. The present studies were conducted to assess whether low-iron diets would affect the deposition of elastic fibers in an in vivo model. One-day-old chicks were fed semipurified diets containing 1.3 (low), 12 (moderate), and 24 (control) mg/kg of iron. After 3 wk, chicks in the low-iron group were underweight and anemic. Their aortas were smaller with significantly thinner walls than control chicks, yet elastin or collagen content did not decrease relative to total protein. They also demonstrated a significantly lower stress-strain resistance than the controls. Electron microscopy demonstrated that aortic and lung smooth muscle cells were vacuolated and surrounded by loose extracellular matrix and disorganized elastic lamellae with diffuse and fragmented networks of elastic fibers and microfibrils. Immunohistology demonstrated that fibrillin-3 (FBN3) was disorganized and markedly reduced in amount in aortas of the low-iron chicks. Elastin messenger RNA levels were not downregulated in the tissues from the low-iron-fed chicks; however, there was a significant reduction in expression of the FBN1 and FBN3 genes compared with control chicks. The studies indicate that iron deficiency had a pronounced negative effect on elastic fiber development and suggests that fibrillin may have an important role in this pathology.}, number={8}, journal={JOURNAL OF NUTRITION}, author={Hill, Charles H. and Ashwell, Chris M. and Nolin, Shelly J. and Keeley, Fred and Billingham, Catherine and Hinek, Aleksander and Starcher, Barry}, year={2007}, month={Aug}, pages={1895–1900} }
 @article{starcher_hill_2005, title={Elastin defects in the lungs of avian and murine models of homocysteinemia}, volume={31}, ISSN={["0190-2148"]}, DOI={10.1080/01902140600611629}, abstractNote={Homocysteinemia in animals is associated with disruption of the elastic fiber component of the extracellular matrix, resulting in vascular complications. The authors have utilized both avian and murine models to investigate the effects of homocysteinemia on lung development and repair following injury. Days old chicks were fed a diet containing 2% methionine for 3 weeks. Pregnant mice were given 2% methionine in the diet and feeding continued for up to 6 weeks after birth. The lungs were removed and examined for defects in elastin fiber formation. Methionine levels were elevated 20-fold in the serum from chicks receiving the methionine and 10-fold in pregnant mice. The elastic fibers in the parabronchi and air capillaries of chicks receiving methionine were thin and clearly disrupted. In the 2% methionine neonatal pups, normal lung development was prevented and the alveoli were significantly enlarged. However, after the pups reached 10 days of age the 2% methionine lungs did not differ histologically from the normal controls. Fetal mice reflected the same serum methionine levels as the dams fed the 2% methionine diet, yet after birth the serum levels of the neonates returned to control levels within 3 days. The authors found that the high serum methionine levels of the dams were not transferred to the milk, allowing the pups to reverse the histopathology observed early and then develop normally. The ability of the lung to replace elastin following elastase injury was not different in mice raised on the 2% methionine diet compared to controls. The studies show that continuous exposure of the developing lung to high circulating levels of methionine/homocysteine can result in major disruptions of elastic fibers and lung architecture. However, young mammals such as the mouse are protected from extended lung pathology because toxic levels of methionine are not transferred through the mothers milk.}, number={9-10}, journal={EXPERIMENTAL LUNG RESEARCH}, author={Starcher, B and Hill, CH}, year={2005}, pages={873–885} }
 @article{starcher_aycock_hill_2005, title={Multiple roles for elastic fibers in the skin}, volume={53}, ISSN={["0022-1554"]}, DOI={10.1369/jhc.4a6484.2005}, abstractNote={ Dermal elastic fibers are believed to have a primary role in providing elastic stretch and recoil to the skin. Here we compare the structural arrangement of dermal elastic fibers of chick skin and different animal species. Most elastic fibers in chick skin are derived from cells that line the feather follicle and/or smooth muscle that connects the pterial and apterial muscle bundles to feather follicles. Elastic fibers in the dermis of animals with single, primary hair follicles are derived from cells lining the hair follicle or from the ends of the pili muscle, which anchors the muscle to the matrix or to the hair follicle. Each follicle is interconnected with elastic fibers. Follicles of animals with primary and secondary (wool) hair follicles are also interconnected by elastic fibers, yet only the elastic fibers derived from the primary follicle are connected to each primary follicle. Only the primary hair follicles are connected to the pili muscle. Human skin, but not the skin of other primates, is significantly different from other animals with respect to elastic fiber organization and probably cell of origin. The data suggest that the primary role for elastic fibers in animals, with the possible exception of humans, is movement and/or placement of feathers or hair. }, number={4}, journal={JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY}, author={Starcher, B and Aycock, RL and Hill, CH}, year={2005}, month={Apr}, pages={431–443} }
 @article{roberson_hill_ferket_2002, title={Effect of intermittent feed deprivation on plasma insulin-like growth factor-1 and tibial dyschondroplasia in broiler chicks}, volume={1}, ISBN={1682-8356}, DOI={10.3923/ijps.2002.22.25}, abstractNote={Two experiments were conducted to evaluate dietary manipulation of growth rate and the subsequent incidence of tibial dyschondroplasia (TD) in broiler chicks. A corn-soybean meal diet which contained 1.15 % calcium and approximately 0.6 % available phosphorus (aP) was fed. In Experiment 1, birds were fed ad libitum or deprived of feed for 8 h during the night either three times per week on Monday, Wednesday and Friday or twice a week on Monday and Friday starting at d 5. In the second experiment, birds were full fed vs depriving feed for 8 h during the day every third day beginning at d 6. Feed deprivation decreased 20-d BW only in Experiment 1 when feed was deprived three times per week. Gain:feed was decreased in both experiments when the birds were restricted fed. The incidence of TD was decreased by 25 to 33 % and the number of severe TD lesions was decreased by 50 to 80 % when feeding time was restricted. Bone ash was not affected in Experiment 1, but was increased in Experiment 2 by feed deprivation. Plasma insulin-like growth factor-I (IGF-I) was decreased by feed deprivation, and returned to control levels after feed was returned. The results indicate that feed deprivation for eight hours at various daily intervals will attenuate the incidence of TD in birds fed a Ca:aP ratio of 2:1. This may be related to temporary reductions in circulating levels of IGF-I.}, number={1}, journal={International Journal of Poultry Science}, author={Roberson, K. D. and Hill, C. H. and Ferket, Peter}, year={2002}, pages={22} }
 @article{hill_mecham_starcher_2002, title={Fibrillin-2 defects impair elastic fiber assembly in a homocysteinemic chick model}, volume={132}, ISSN={["0022-3166"]}, DOI={10.1093/jn/132.8.2143}, abstractNote={Homocysteinemia in humans is associated with vascular complications that increase the risk for atherosclerosis and stroke. Animal studies have shown that the disease is multifactorial and includes lesions associated with the elastin component of the extracellular matrix. In the following experiments we have used the aortas from rapidly growing chicks to assess the cause of the elastin defects resulting from homocysteinemia. Day-old chicks were fed diets containing varying amounts of DL-methionine, DL-homocysteine, homocysteine thiolactone or DL-cysteine for periods up to 9 wk. Three weeks after feeding 2% DL-methionine the plasma methionine was elevated > 20-fold, whereas plasma homocysteine was more than 3-fold normal plasma values. The aortas showed severe histopathology, evidenced by the pronounced separation of elastic lamellae with marked smooth muscle proliferation and, in some instances, aneurysms. There was no evidence of decreased desmosine content or a significant reduction in lysyl oxidase in the aortas from the treated groups compared to those from controls. Increasing other dietary factors such as the vitamins required for methionine metabolism had no effect on the development of the vascular lesions. Twenty to 30% of the chicks fed the high methionine diets exhibited severe neurological problems, expressed as tonic contractions or seizures. Electron microscopy revealed disordered aortic elastic fibrils, associated with either an absence of or disrupted assembly of microfibrils. Immunohistochemical studies demonstrated a loss of fibrillin-2 immunoreactivity in the aortas of chicks fed 2% methionine. The studies suggest that elevated plasma methionine or its metabolites disrupt normal microfibril configuration, leading to the assembly of aberrant elastic fibers.}, number={8}, journal={JOURNAL OF NUTRITION}, author={Hill, CH and Mecham, R and Starcher, B}, year={2002}, month={Aug}, pages={2143–2150} }
 @article{starcher_conrad_hinek_hill_1999, title={Antibody raised to AKAAAKAAAKA sequence on tropoelastin recognizes tropoelastin but not mature crosslinked elastin: A new tool in metabolic and structural studies of elastogenesis}, volume={40}, ISSN={["0300-8207"]}, DOI={10.3109/03008209909000705}, abstractNote={Tropoelastin, which is secreted from the cell in a soluble form, contains specific alanine rich repeat domains that are destined to form covalent desmosine and isodesmosine crosslinks in mature insoluble elastin. We raised a monospecific polyclonal antibody to a AKAAAKAAAKA synthetic peptide (AKA) which represents this alanine rich region of tropoelastin. The antibody was reactive with the original peptide antigen and purified tropoelastin, but not with mature crosslinked elastin isolated from several animal species. Conditioned media from chick aorta smooth muscle cells in culture reacted in an ELISA with the AKA antibody, but only in the presence of BAPN to block the conversion of the epsilon-amino groups to aldehydes. Immunofluorescence demonstrated that the AKA antibody decorated newly deposited tropoelastin assembled in fine fibrils in matrix produced by cultured human skin fibroblasts. EM-immunogold specifically localized this antibody to the immature elastic fibers present in fetal sheep ductus arteriosus. Moreover, immunohistochemistry demonstrated that the antibody recognized nonpolymerized tropoelastin assembled on the periphery of elastic fibers in the aorta of chicks raised on copper deficient and BAPN containing diets. These studies demonstrate that this new anti-tropoelastin antibody can be used as a useful tool to investigate elastin metabolism where it is important to distinguish between tropoelastin and mature crosslinked elastin.}, number={4}, journal={CONNECTIVE TISSUE RESEARCH}, author={Starcher, B and Conrad, N and Hinek, A and Hill, CH}, year={1999}, pages={273-+} }
 @article{qureshi_hill_heggen_1999, title={Vanadium stimulates immunological responses of chicks}, volume={68}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(99)00010-0}, abstractNote={In a continuation of studies on the interaction of dietary phosphorus (P) and vanadium (V) levels, studies have directed toward an examination of this interaction on the immune system of chicks. Antibody titers to sheep red blood cells (SRBC) were increased at 7 days post-inoculation (PI) by as little as 10 mg V/kg diet in the P-deficient group, while 50 mg V/kg was required in the P-supplemented group. At 14 days PI, only the 50 mg V/kg was significantly higher in both P-deficient and P-supplemented groups. At 21 days PI, vanadium had no significant effect. P-deficiency resulted in a decrease in the percentage of phagocytic macrophages obtained from the abdominal cavity and a decrease in the number of intracytoplasmic SRBC per phagocytic macrophage. These two criteria were increased by vanadium in both the P-deficient and P-supplemented animals. In P-supplemented animals, the CD4/CD8 ratios of lymphocytes obtained from the blood and spleen were increased by the inclusion of 50 mg V/kg diet. The IL-l-like activity of macrophage supernatants was not significantly affected by dietary V, but IL-6 activity was increased. Densitometric analysis of lysates of macrophages isolated from control and V-fed chicks for anti-protein-tyrosinephosphate (PTP) bands indicate that dietary V increased PTP. While the evidence is not clear that there is a P × V interaction in the immune system studies, it is clear that dietary V at the levels used results in a positive immune response of chicks, possibly mediated through increased PTP.}, number={1}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Qureshi, MA and Hill, CH and Heggen, CL}, year={1999}, month={Mar}, pages={61–71} }