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Biomedical subjects

K M Reiser

Publications and source records attributed to K M Reiser.

At least 55 records · Page 3Linked to original sources
PubMed1984

Ozone exposure, food restriction and protein deficiency: changes in collagen and elastin in rodent lung.

Two groups of weanling or young adult rats were fed ad lib casein-based diets containing 4 or 16% protein. Food was restricted in a third group (fed the 16% protein diet) to the amount consumed daily by rats (adult or weanlings) fed the 4% diet. After 3 weeks (weanlings) or 1, 3 or 5 weeks (adults), one-half of the rats in each group were exposed to 0.64 ppm (1.28 mg/m3) of ozone for 7 days (23.5 h each day). Several parameters were then evaluated related to lung connective tissue metabolism including: (1) total lung hydroxyproline, (2) total lung elastin, (3) apparent rates for lung collagen synthesis and elastin accumulation and (4) lung and body weights. In general, the response to protein deficiency and food restriction was more pronounced than to ozone exposure. Protein deficiency and food restriction resulted in decreased lung size and collagen content. However, the ability of lung to respond to ozone (in relative terms) was not altered by changes in diet as assessed by changes in lung weight or the collagen synthetic rate.

Animals↗
PubMed1984

Elevated ratios of type I/III collagen in the lungs of chronically ventilated neonates with respiratory distress.

Increased synthesis of type I collagen, leading to increased ratios of type I to type III collagen in the lungs, has been observed in the lungs of animals with experimental pulmonary fibrosis. Similar changes in collagen type ratios have been observed in lungs of humans dying of idiopathic pulmonary fibrosis and of adult respiratory distress syndrome. In this study, lung collagen type ratios were examined in infants with acute and chronic lung disease. Tissue from the right lower lobes of neonates was obtained post mortem. Specific collagen types were quantitated by solubilization of lung collagen with CNBr and fractionation of the resulting mixture of peptides by column chromatography and polyacrylamide gel electrophoresis. Ratios of type I/III collagen were calculated for each lung sample using two independent pairs of marker peptides for these determinations. In some cases the ratio of type V to type III collagen in these same lung samples was also quantitated. We observed a significant increase in the ratio of type I/III collagen in infants with a premortem diagnosis of chronic lung disease, usually preceded by respiratory distress syndrome. We also observed two infants with large changes in collagen type ratios who might have had pulmonary fibroplasia secondary to intrauterine lung disease. These data suggest that there may be several subsets of infants with respiratory distress syndrome, each having a different prognosis.

Chronic Disease↗
PubMed1984

Collagen biosynthesis.

Collagen is the major structural protein of the lung. At least five genetically distinct collagen types have been identified in lung tissue. However, the precise role of collagen in nonrespiratory lung function is not well understood, in part because of the difficulties inherent in studying lung collagen, regardless of the type of assay used. A major problem is the insolubility of lung collagen; generally less than 20% of total lung collagen can be solubilized as intact chains, even with harsh extraction procedures. Since such collagen may not be representative of total lung collagen, errors in quantitating collagen types, for example, may arise from using such material. Measurement of total lung collagen content may also pose problems, unless appropriate parameters of normalization are chosen. Biopsy dry weight, protein content, and DNA content, for example, may all change in certain disease states. Despite these difficulties, a number of changes in lung collagen have been documented in experimental pulmonary fibrosis, including increased collagen content, increased collagen synthesis rates, and changes in collagen type ratios. Many questions remain. For example, why do diverse toxic substances appear to cause essentially the same fibrotic response, even though initial sites of damage may vary? Conversely, why do similar toxic substances, such as ozone and NO2, cause diverse responses (fibrosis and emphysema, respectively)? Much work remains to be done to elucidate the mechanisms underlying the lung's choice of response.

Air Pollutants↗
PubMed1983

Type V collagen. Quantitation in normal lungs and in lungs of rats with bleomycin-induced pulmonary fibrosis.

Type V collagen was first isolated in 1976; there is still controversy as to how many molecular species of type V collagen exist. Although its structural and functional roles remain unclear, reports of changes in the relative amount of type V collagen from that present in normal tissue have been reported in such diverse pathologic conditions as atherosclerotic aortas, prolapsed mitral valves, and fibrotic lungs. Methods for quantitating type V collagen relative to other collagens have consisted of solubilizing the collagen with pepsin and then analyzing the ratios of the intact chains by gel electrophoresis or by column chromatography. In tissues in which only a small percentage of the total collagen can be solubilized by pepsin, such analyses may not accurately reflect changes in the total collagen present. In this report, a method for quantitating type V collagen relative to types I and III collagens based on CNBr peptide mapping is presented. CNBr solubilizes virtually all the collagen present in any tissue. The method is applied to a model of bleomycin-induced pulmonary fibrosis in rats. It was found that type I collagen increased relative to types III and V collagens, which seemed to remain at values comparable to those observed in lungs from control (normal) rats, both in terms of newly synthesized collagen (collagen synthesized by lung minces during 4 h in culture) and total unlabeled lung collagen (collagen synthesized during the life of the animal).

Amino Acids↗
PubMed1983

Protein deficiency: effects on lung mechanics and the accumulation of collagen and elastin in rat lung.

Groups of weanling (approximately 50 g) or young adult (approximately 300 g) rats were fed ad libitum casein-based diets varying in protein content from 4 to 16%. A group was also fed the 16% protein diet in an amount on a daily basis restricted to that consumed by the protein-deficient group (4% protein). The rats were fed the diets for either 4 weeks (weanling) or 6 weeks (adults). Protein-deficient or "food-restricted" rats (whether weanling or adults) were smaller and had smaller lungs than rats fed ad libitum the diets containing 16% protein. The lung elastin content was more resistant to dietary manipulation than was the lung collagen content. Lung collagen was significantly decreased in both weanling and adult rats fed the 4% protein diet. In weanling rats, pressure-volume relationships derived from saline-filled lungs (analyzed by exponential curve-fitting methods) suggested that lungs from food-restricted rats may be less compliant than lungs from rats fed the control diet ad libitum. When expressed in absolute terms, lungs from protein-deficient rats also appeared to be less compliant than normal rats; however, on a relative basis (percentage of volume at a given recoil pressure or the expression of volume on a weight basis) differences in compliance were less apparent. It is proposed that in weanling rats the differences in lung composition and compliance are the result of retarded lung growth and perhaps development.

Age Factors↗
PubMed1983

Type I collagen content is increased in lungs of patients with adult respiratory distress syndrome.

Collagen in lung tissue was examined from patients with adult respiratory distress syndrome, from patients who did not have this disease but required mechanical ventilation and oxygen treatment, and from patients without overt lung disease. Cyanogen bromide peptide mapping techniques were used to determine the ratio of type I to type III collagen present in these lungs. In the fibrotic lungs from patients with adult respiratory distress syndrome a shift was found in the ratio of type I to type III from the normal value of 2:1 to a mean value of 3.4:1. In patients with normal lungs and those with other lung diseases collagen type ratios were normal. Our data suggest that (i) changes in lung collagen of patients with adult respiratory distress syndrome resemble those previously described in patients with idiopathic pulmonary fibrosis, although the changes occur much more rapidly in the former; (ii) the increased content of collagen in lungs of patients with adult respiratory distress syndrome shown by others is predominantly of type I collagen; and (iii) the stimulus to the lung to produce excess type I collagen relative to type III is not solely of iatrogenic origin--that is, resulting from oxygen or ventilator treatment.

Adult↗
PubMed1983

Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism.

Changes in cell proliferation and in collagen synthesis were studied in young adult male BALB/c mice injected intraperitoneally with 400 mg/kg of butylated hydroxytoluene (BHT) in corn oil or corn oil alone and immediately exposed to 70% oxygen or air for 6 days. Mice received [3H]thymidine either as a single injection 90 min before being killed or as a continual infusion via an osmotic minipump. Autoradiography was done 2 to 14 days after BHT injection, and cell kinetic studies were performed. In a similar experiment, mice were injected intraperitoneally with [3H]proline 3 h before being killed, and type l/type III collagen ratio in newly synthesized lung collagen was determined. We found that exposure to 70% oxygen immediately after the administration of BHT initially delayed the epithelial cell proliferation and the decrease in the percentage of newly synthesized type III collagen that occurred after BHT alone. Once the animals were removed from oxygen there was a compensatory burst of cell proliferation and a precipitous drop in the percentage of newly synthesized type III collagen. The proliferating cell population after removal from oxygen was primarily interstitial and not epithelial. When exposure to oxygen was delayed, cell proliferation was similar to that seen after BHT injection alone.

Animals↗
PubMed1983

Anomalous electrophoretic behavior of a cyanogen bromide peptide from type III collagen.

The relationship between relative mobility on sodium dodecyl sulfate-polyacrylamide gels and the logarithm of molecular weight was linear for peptides derived by CNBr cleavage from purified collagen chains. One striking exception was found: when the CNBr peptide alpha 1(III)CB-8 was subjected to electrophoresis on a polyacrylamide slab gel calibrated with other peptides derived from the type III collagen chain, its relative mobility corresponded to a molecular weight of approximately 8,000. On a gel calibrated with globular proteins, its apparent molecular weight was 12,000. Its actual molecular weight, as determined by gel filtration and by amino acid analysis, is approximately 12,000. The dodecyl sulfate-protein binding ratio for this peptide did not differ from that of other collagenous peptides or globular proteins. Free electrophoretic mobilities and retardation coefficients were determined for selected collagenous peptides and globular proteins by electrophoresis on tube gels of different concentrations of acrylamide. By these indices, alpha 1(III)CB-8 resembled a globular protein rather than a collagenous peptide. Presumably, some difference in primary structure of this peptide results in conformational changes of its complex with dodecyl sulfate, such that the peptide-dodecyl sulfate complex behaves more like a globular protein than a collagenous peptide on polyacrylamide gels.

Amino Acids↗
PubMed1983

Experimental silicosis. II. Long-term effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs.

Rats received intratracheal instillations of 50 mg of silica (quartz, 0.5 mu particles). One, 2, 4, 5, 6, 9, and 12 months later, the lungs were evaluated histologically and by various biochemical measurements. The lung content of protein, proline, and hydroxyproline (collagen) were quantitated, as were the synthesis rates of lung collagen and the total lung protein (evaluated with lung minces in vitro. The ratio of newly synthesized and of total lung Type I to Type III collagen was also determined. These experiments were performed in parallel on rats free of chronic respiratory disease and a strain of conventional animals. The authors conclude that 1) the excess collagen deposited in granulomas and/or silicotic nodules as part of the fibrotic response of the lung is similar to normal lung collagen with respect to relative ratios of Types I and III present, in contrast to the response of the lung to oxidant pneumotoxins; 2) the response of the lung to silica continues for at least 1 year; 3) there are essentially no differences in the response of chronic respiratory disease-free Sprague-Dawley and conventional Wistar rats to intratracheally instilled silica. Both strains of rats develop silica-containing granulomas, mature silicotic nodules, and areas of alveolar lipoproteinosis associated with interstitial pneumonitis. Even 1 year after instillation of silica areas of granulomas, silicotic nodules and alveolar lipoproteinosis may be observed in most of the lungs studied; ie, these responses are not mutually exclusive.

Animals↗
PubMed1982

Long-term morphologic and biochemical features of experimentally induced lung fibrosis in the mouse.

Mice were injected with 400 mg. per kg. of butylated hydroxytoluene (BHT) and exposed to an atmosphere of 70 per cent oxygen for 6 days. Control groups were animals treated with BHT alone or injected with vehicle and kept for 6 days in either O2 or air. Animals were killed at various time intervals after BHT treatment, and the lung changes were evaluated with biochemical and morphologic techniques. In animals exposed to BHT + O2, there was initially a diffuse interstitial pneumonitis, increased levels of interstitial collagen, and a decreased ratio of type III to type I collagen. With time the inflammatory component subsided, and degenerative changes primarily consisting of dilation of terminal airways and of alveoli became apparent. Elevated levels of lung hydroxyproline persisted until the termination of the study at 1 year, although ratios of type III to type I collagen returned to normal. In animals treated with BHT alone, collagen accumulation and morphologic changes were similar, although much less severe. It is concluded that potentiation of acute lung injury by oxygen produces long-lasting morphologic and biochemical alterations in lung parenchyma.

Animals↗
PubMed1982

Experimental silicosis. I. Acute effects of intratracheally instilled quartz on collagen metabolism and morphologic characteristics of rat lungs.

Rats were intratracheally instilled with 50 mg of silica as quartz (0.5-mu particles) at day 0. One and 2 weeks later, lungs were evaluated histologically and by a variety of biochemical measurements. Protein, proline, and hydroxyproline content (as an index of total lung collagen) were quantitated, as were the lung collagen synthesis rate and the total lung protein biosynthesis rate (evaluated with lung minces in vitro). The ratio of newly synthesized Type I/Type III collagen was determined, as was the same ratio for total lung collagen. These experiments were performed in parallel on chronic respiratory disease-free rats and in a strain of conventional animals. The authors conclude that 1) changes in lung structure and composition can be appreciated as early as 1 week, the earliest time point studied, after intratracheal instillation of 50 mg of quartz; 2) observed morphologic changes during the first 2 weeks are consistent with biochemical changes; 3) there are essentially no differences in the response of chronic respiratory disease-free Sprague-Dawley and conventional Wistar rats to intratracheally instilled silica. Both strains of rats developed silica-containing granulomas, which ultimately developed into silicotic nodules, as well as areas of alveolar lipoproteinosis associated with interstitial pneumonitis.

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↗
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↗