Biomedical subjects

Barry Starcher

Publications and source records attributed to Barry Starcher.

21 records · Page 2Linked to original sources

PubMed2002

Fibrillin-2 defects impair elastic fiber assembly in a homocysteinemic chick model.

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.

Animal Feed↗

PubMedDate not supplied

Combining histology and biochemical measurements of connective tissue components in small samples of lung: application to bleomycin-induced fibrosis in the mouse.

Bleomycin-induced lung injury in mice was used to illustrate the plausibility of quantitating changes in elastin or protein concentration in histologically defined regions of mouse lungs. Mice were instilled by either the intranasal or intratracheal route with varying levels of bleomycin and the lungs were removed and fixed under pressure for histology and analysis. Histological sections that bracketed a defined volume of tissue was used for biochemical analysis and was limited to the alveolar region of the lung. Our studies showed that the intranasal method of instillation was as effective as the intratracheal method for inducing fibrosis. Even though distribution to the 4 major lobes of the lung was fairly uniform, there was no consistency in the degree of fibrosis between the various lobes of the same animal. The most dramatic change in biochemical parameters was protein concentration, which increased over 10-fold in some fibrotic lungs compared to normal lungs, whereas desmosine concentration increased up to 5-fold. Fibrosis scores agreed well with desmosine concentration, except with moderate desmosine increases where histologically defined fibrosis was not observed. The experiments illustrate the feasibility and desirability of comparing histology and biochemical analysis on the same fixed lung sample.

Administration, Inhalation↗

PubMedDate not supplied

Elastin defects in the lungs of avian and murine models of homocysteinemia.

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.

Animals↗