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Biomedical subjects

J A Last

Publications and source records attributed to J A Last.

At least 109 records · Page 6Linked to original sources
PubMed1981

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↗
PubMed1981

Ozone-induced acute pulmonary fibrosis in rats. Prevention of increased rates of collagen synthesis by methylprednisolone.

The net rate of collagen synthesis by lung minces prepared from rats exposed for 7 days to 0.8 to 1.5 ppm (1.6 to 3.0 mg/m3) of ozone was increased in a dose-dependent manner severalfold above the net rate obtained with lung minces prepared from rats that had breathed only filtered air. Concurrent administration of methylprednisolone (1 to 50 mg/kg/day) during the exposure to ozone prevented the increase in rate of collagen synthesis in a dose-dependent manner for each level of ozone tested. These results could be correlated with lower levels of inflammatory edema measured in the same steroid-treated rats as decreased wet weights of their right apical lung lobes. We conclude that acute pulmonary fibrosis caused by exposure of rats to high levels of inspired ozone can be partially or completely prevented, depending on the severity of the insult, by simultaneous administration of high levels of the anti-inflammatory steroid methylprednisolone.

Animals↗
PubMed1981

Pulmonary fibrosis in experimental acute respiratory disease.

Changes in collagen metabolism were examined in 3 models of acute respiratory disease in rats. Fibrotic changes in the lungs of rats were provoked by exposing them to paraquat (intraperitoneal), ozone (inhaled), or bleomycin (intratracheally injected). After an interval sufficient to allow histologically discernible fibrosis to occur (6 to 7 days), lungs were removed from the rats, and apparent collagen synthesis rates were determined with cultured lung minces incubated in medium containing 3H-proline. There was a significant increase (severalfold in the apparent collagen synthesis rates by lung minces from all the pneumotoxin-exposed rats in this study. Portions of the 3H-proline-labeled lung minces were then used for quantifying ratios of Type I to Type III collagen. Using CNBr mapping techniques and a combination of carboxymethylcellulose chromatography and polyacrylamide gel electrophoresis, we quantified Type I/Type III collagen for newly synthesized, 3H-labeled collagen as well as for total unlabeled collagen. In lung minces from normal rats, the ratio was 2:1 (65 to 70% Type I collagen) for both newly synthesized and total collagen. On the other hand, lung minces prepared from fibrotic rats accumulated a mixture of newly synthesized collagens that was substantially enriched for Type I collagen (80 to 85% Type I). There was no change in Type I/Type III collagen for total unlabeled collagen, nor was there any detectable increase of total collagen per lung after 1 wk. We conclude that an early event in experimental acute respiratory disease is a marked increase in the relative synthesis of Type I collagen; this shift occurs before there is observable increased accumulation of collagen in the lung.

Acute Disease↗
PubMed1980

Mucus glycoprotein secretion by tracheal explants: effects of pollutants.

Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with [3H] glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I-IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques.

Air Pollutants↗
PubMed1980

Glycoprotein synthesis by an established cell line from hamster tracheal epithelium.

A cloned cell line, HTE-B, derived from hamster tracheal epithelium, synthesizes and secretes labeled glycoproteins in tissue culture. The glycopeptides derived from these glycoproteins by papain treatment are chromatographically and electrophoretically indistinguishable from those derived from glycoproteins secreted by cultured tracheal explants from rats or humans. The availability of this cell line should allow us to greatly increase our understanding of the mechanisms of glycoprotein synthesis and secretion by respiratory epithelial cells, and the underlying control mechanisms governing these processes.

Animals↗
PubMed1979

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↗
PubMed1979

Silicosis and fibrogenesis: fact and artifact.

Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis.

Animals↗