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Biomedical subjects

C E Cross

Publications and source records attributed to C E Cross.

At least 127 records · Page 7Linked to original sources

Interactions of ascorbic acid supplementation and bleomycin instillation on murine lung connective tissue metabolism.

The effects of ascorbic acid supplementation on the pulmonary toxicity induced by bleomycin were examined. Swiss-Webster mice were fed an ascorbate-free diet supplemented with ascorbic acid at 0%, 0.2%, or 1.0% of the diet for 2 weeks. Bleomycin (0.15 units) was instilled intratracheally and the mice were killed 1 week later. Bleomycin caused pulmonary inflammation and edema as noted by the increases in lung wet weight and lung wet-weight-to-dry-weight ratios. The activity of prolyl hydroxylase was increased 1.4-fold to 1.6-fold in response to bleomycin, but only minor increases were observed in the collagen and elastin content of the lung. Prior dietary ascorbic acid supplementation did not reverse the effects induced by bleomycin. Interestingly, each dietary level of supplemental ascorbic acid resulted in a slight increase in the elastin and collagen content of the lung in comparison with lungs from mice consuming no ascorbic acid in their diet. The data suggest that high levels of ascorbic acid supplementation may aggravate the response to bleomycin.

Animals↗

Characterization of sheep lung lymph lipoproteins: chemical and physical properties.

We have determined the composition and distribution of plasma and lung lymph lipoproteins from unanesthetized ewes. Cholesterol, triglyceride, and phospholipid levels in lung lymph were 45%, 50%, and 50%, respectively, of those in plasma. Lipoproteins from both lymph and plasma were separated into two major fractions: d less than 1.063 g/ml or "LDL", and d 1.063-1.21 g/ml or HDL. HDL was the major lipoprotein species in the plasma and lymph. Gradient gel electrophoresis of HDL on 4-30% gels showed that, in lymph, HDL particles were shifted to larger sizes; in addition to a peak at 8.5 nm, which was similar to plasma HDL, there were two additional components of larger size, one at 9.2 nm and the other at 12 nm. Electron microscopy revealed that lymph HDL contained two new particles not seen in plasma: large, round particles, 13.6 nm diameter, and discoidal particles, 18.7 by 4.9 nm, long and short axis, respectively. Compositional analysis of lymph HDL revealed a relative enrichment in free cholesterol as well as an enrichment in apolipoprotein E. Lymph "LDL" on gradient gel electrophoresis was extremely heterogeneous. Several peaks were evident in the 23-30 nm size range (similar to plasma "LDL"), but a supplementary component at approximately 15-16 nm was also present. Whereas plasma "LDL" on electron microscopy contained only round particles 26 nm in diameter, lymph contained an additional, unusual particle which was close-packed, with square geometry, and was 15 nm in diameter. Lymph apolipoprotein composition differed from that of plasma by the appearance of apoE and A-I as well as apoB. Particles containing apoE and A-I were separated from apoB-containing particles in a fraction of d 1.047-1.063 g/ml by density gradient centrifugation. On electron microscopy, this fraction revealed square-packing particles; the density and apolipoprotein composition suggest that these unusual particles are a continuum of HDL. Changes in the physical and chemical properties of lung lymph lipoproteins suggest that these particles are metabolically modified.

Animals↗

Lipoprotein distribution in sheep lung lymph.

The composition of lymph draining the sheep caudal mediastinal lymph node is believed to reflect the composition of lung interstitial fluid. Although long-term lymph fistulas have been extensively utilized in studies related to lung microvascular fluid and protein flux, attention has thus far not been focused on lipoproteins as they might appear in lung interstitial space. We therefore characterized the lipoprotein distributions and measured triglyceride and cholesterol concentrations of lung lymph and plasma in nine unanesthetized sheep with long-term embedded instrumentation. We also measured triglyceride and cholesterol concentrations in prefemoral and thoracic duct lymph. The plasma LDL concentration was 55.3 +/- 20.2 mg/dl and HDL concentration was 99.9 +/- 27.2 mg/dl. By comparison, the lung lymph LDL concentration was 27.7 +/- 3.0 mg/dl and the HDL concentration was 45.4 +/- 11 mg/dl. The major sheep lipoprotein classes (LDL, HDL), although low in concentration compared to humans, are present in lung lymph in relative proportions similar to those of plasma. Analytical ultracentrifugation revealed the presence of a fast-floating component in lung lymph HDL that was not present in plasma. Electron microscopy showed two sizes of particles in lung lymph HDL, 135A and 97A, which probably correspond to the fast-floating and slow-floating components, respectively; plasma HDL contained only 94 A particles. Changes in the physical properties of HDL present in lung lymph suggest modification of the HDL either in the endothelial barrier or interstitial fluid of the lung.

Animals↗

Elastin metabolism in rodent lung.

Data from the in vivo incorporation of [3H]valine into fractions of elastin obtained from rat or mouse lung suggest that postnatal lung elastin synthesis occurs predominantly in the first 1 to 2 weeks of life. Very little [3H]valine was incorporated into lung elastin obtained from adult animals. When lung elastin from neonatal mice was radiochemically labelled with [14C]lysine as a single pulse, it was observed that the specific activity of the elastin expressed as the total dpm values as 14C per mg was not significantly altered over a 6 month period. Elastin appears to turn over very slowly in mouse lung with half-life best estimated in years.

Animals↗

Partial characterization of a tropoelastin precursor isolated from chick aorta.

Evidence is presented that indicates tropoelastin is derived from a soluble elastin with a molecular weight of 95000. Tropoelastin and its proposed precursor were isolated from the aortas of copper-deficient chicks. Although it is doubtful that the proposed precursor is an initial product of elastin translation, i.e., a proelastin, it is proposed to be at least a truncated form of proelastin that is converted to tropoelastin. The key to its isolation was the presence of alpha 1-antitrypsin at each step in the purification procedure. The first 11 amino acid residues at the NH2 terminal of the proposed tropoelastin precursor (GGVPGVAVPGGV) are the same as those for tropoelastin. Its amino acid composition is similar to that of tropoelastin, except for higher amounts of acidic amino acid residues. Further, the proposed precursor contains a limited number of aldehydic functions, presumably in the form of peptidyl allysine. This was taken as an indication that the proposed precursor serves as a substract for lysyl oxidase. Under the conditions used for the isolation, the precursor appeared to be in higher concentrations than tropoelastin in aorta extracts from copper-deficient chicks.

Amino Acid Sequence↗

Composition of glycoproteins secreted by tracheal explants from various animal species.

1. The acidic and neutral glycoproteins secreted by cultured tracheal explants from pigs, sheep, rats, mice, monkeys, guinea pigs, dogs and chickens were purified and fractionated by column chromatography on DEAE-cellulose and by electrophoresis on cellulose acetate. 2. The ratios of acidic to neutral mucus glycoproteins were compared for the above animals with that of mucus glycoproteins secreted by cultured human bronchi. 3. The observed ratios of acidic to neutral glycoproteins ranged from 4.0 (mouse) to 7.2 (chicken and pig) from cultured tracheae; secreted human bronchial mucus had a ratio of 2.7. 4. The ratio of acidic to neutral glycoproteins secreted by tracheal explants varied with duration of incubation of the trachea in culture.

Animals↗

A new model for health effects of air pollutants: evidence for synergistic effects of mixtures of ozone and sulfuric acid aerosols on rat lungs.

Chronic respiratory disease-free rats were exposed to relatively low levels of ozone (0.4 to 0.5 ppm) and H2SO4 aerosols (11 to 3,000 microgram/m3) and to mixtures of these pollutants. We independently evaluated exposure effects on conducting airway metabolism as rate of secretion of mucus glycoproteins by tracheal explants and on lung homogenates (predominantly lung parenchyma) by various chemical assays. True synergism was observed in that the response to the mixture of gases exceeded the sum of effects observed with the same concentration of either gas alone. Wet to dry weight ratios; DNA, protein, and RNA content; and the activities various lysosomal hydrolases in the lung homogenate all increased upon exposure to O3-H2-SO4 mixtures concomitant with observed increases in the rate of secretion of mucus glycoproteins by tracheal explants from the same rats. Preliminary experiments suggest that all of these effects are reversible when rats are allowed to recover after exposure. We conclude that the lack of toxicity noted upon exposure of experimental animals to individual pollutant gases at near-ambient levels should be interpreted with caution, since there is now epidemiological, physiological, and biochemical evidence that mixtures of pollutant gases may show synergistic effects.

Aerosols↗

Effect of butylated hydroxytoluene and other antioxidants on mouse lung metabolism.

Toxic doses of butylated hydroxytoluene (BHT), a phenolic antioxidant commonly used as a food additive, are known to produce lung damage. In this study, 3 days after a single ip injection of 62.5, 215, or 500 mg/kg BHT in mice there was a dose-dependent increase in lung weight. This concentration dependence with injected BHT was accompanied by increases in lung DNA and nonprotein sulfhydryl levels and in whole lung tissue enzyme activities of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and superoxide dismutase. The increased enzyme activities are considered to correspond to inflammatory and proliferative pulmonary changes resulting from acute lung cell injury and necrosis, which have been described previously, and cannot be construed as evidence for a primary oxidant-induced pulmonary lesion. The mechanism of BHT-induced lung changes may not be related to the antioxidant property of BHT, since vitamin E, n-propyl gallate, ethoxyquin, N,N'-p-phenylenediamine, and the structurally similar compound, butylated hydroxyanisole did not appear to produce the gross anatomical or biochemical lung changes observed with BHT.

Animals↗