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Biomedical subjects

N K Tyler

Publications and source records attributed to N K Tyler.

29 records · Page 2Linked to original sources
PubMed1989

Cytodifferentiation of two epithelial populations of the respiratory bronchiole during fetal lung development in the rhesus monkey.

This study describes the cytodifferentiation of the two populations of epithelial cells found in the respiratory bronchiole of the adult rhesus monkey. One population, pseudostratified and containing ciliated, nonciliated secretory, and basal cells, is found overlying the pulmonary artery (PA). The other population, not associated with the PA, contains nonciliated cuboidal cells between alveolar outpockets. In this study we used terminal conducting airways from the lungs of fetal (90 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys. Ciliated cells were partially differentiated at 90 DGA (54% gestation) and completely differentiated by 134 DGA (80% gestation). Nonciliated secretory cells were partially differentiated at 95 DGA (57% gestation) but did not lose all glycogen until the postnatal period. Basal cells appeared by 134 DGA (80% gestation) and matured in the postnatal period. Small mucous granule cells appeared at 125 DGA (74% gestation) and did not change throughout fetal development. Neuroendocrine cells were present throughout the entire period studied. Nonciliated cuboidal bronchiolar cells of the nonciliated population of the respiratory bronchiole appeared at 105 DGA (62% gestation) and matured in the postnatal period. We conclude that 1) although most of the differentiation of the lower airway occurs before birth, most of the cell types are not completely differentiated at birth; 2) the sequence of differentiation for the cells of the ciliated pseudostratified epithelial population is ciliated, nonciliated secretory, and basal; 3) the sequence of differentiation for the nonciliated secretory cell is similar to that of the secretory cells in more proximal airways; and 4) basal, neuroendocrine, and small mucous granule cells are not a part of the differentiation sequence of the other cell types.

Animals↗
PubMed1988

Morphogenesis of the respiratory bronchiole in rhesus monkey lungs.

The epithelium of the respiratory bronchiole in the adult rhesus monkey consists of two populations: a pseudostratified epithelium with basal, mucous goblet, and ciliated cells located near the pulmonary artery (PA); and a simple cuboidal epithelium composed only of nonciliated bronchiolar epithelial (or Clara) cells in areas away from the PA. This study describes the pattern of differentiation of these two epithelial populations, and their relationship to the PA and to the time of appearance of alveoli in the respiratory bronchiole of the rhesus monkey during the period of 90-125 days gestational age (DGA). These events were related to changes in the adjacent parenchyma. Dissected airways of infusion-fixed, critical-point-dried lungs were evaluated by scanning microscopy followed by light microscopy of the same airways. At 54% of gestation (90 DGA), the distal airway was lined by a mixture of ciliated and nonciliated cells. By 67% of gestation (110 DGA), the ciliated cells were confined to the epithelium over the PA. The underlying connective tissue initially was cellular containing few fibers but was fibrous by 76% of gestation (125 DGA). Alveolarization began near the most distal cartilage at 57% of gestation (95 DGA), the same period at which secondary septation occurred in the distal acinus. Thus, alveolarization occurred simultaneously in two centers: 1) the proximal centriacinar region in the vicinity of the most distal cartilage and 2) the distal lung parenchyma. The duration of centriacinar alveolarization was short, approximately 5 days.

Animals↗
PubMed1988

Comparison of daily and seasonal exposures of young monkeys to ozone.

Oxidant air pollution tends to occur in both seasonal and daily cycles of polluted and clean air. To compare the effects of these 2 cycles, we exposed 2 groups of 7-month-old male monkeys to 0.25 ppm (0.49 mg/m3) of ozone (UV photometric standard) 8 h/day either daily or, in the seasonal model, days of alternate months during a total exposure period of 18 months. This is a longer ozone exposure period than any previously reported. A control group breathed only filtered air. Young monkeys were studied as their lungs are similar to those of man and their lungs, like those of man, grow over a period of several years. Monkeys from the seasonal exposure model, but not those exposed daily, had significantly increased total lung collagen content, chest wall compliance, and inspiratory capacity. All monkeys exposed to ozone had respiratory bronchiolitis with significant increases in related morphometric parameters. The only significant difference between seasonal and daily groups was in the volume fraction of macrophages. Even though the seasonally exposed monkeys were exposed to the same concentration of ozone for only half as many days, they had larger biochemical and physiological alterations and equivalent morphometric changes as those exposed daily. Lung growth was not completely normal in either exposed group. Long-term effects of oxidant air pollutants which have a seasonal occurrence may be more dependent upon the sequence of polluted and clean air than on the total number of days of pollution. Estimations of the risks of human exposure to seasonal air pollutants from effects observed in animals exposed daily may underestimate long-term pulmonary damage.

Air Pollutants↗
PubMed1988

Effect of murine gamma interferon on the cellular responses to bleomycin in mice.

Because in vitro studies have shown inhibition of fibroblast proliferation and collagen synthesis by interferon, we tested the hypothesis that murine gamma interferon inhibits bleomycin-induced pulmonary fibrosis in mice. Mice were divided into the following groups: saline plus vehicle (27), saline plus interferon (29), bleomycin plus vehicle (26), and bleomycin plus interferon (26). Bleomycin or saline were given intratracheally once at the beginning of the experiment and vehicle (phosphate-buffered saline) or interferon was given intramuscularly daily. Mice were killed at 14 or 21 days of the experiment. About half of the mice from each group were used for collagen biochemistry and half for bronchoalveolar lung lavage, transmission electron microscopy (TEM), and morphometry. Hydroxyproline content showed a significant reduction in bleomycin plus interferon compared to bleomycin plus vehicle mice at 21 days. The saline plus vehicle and saline plus interferon mice showed no difference in hydroxyproline content. Similarly, bronchoalveolar lavage showed no differences between saline plus vehicle and saline plus interferon mice; however, all mice treated with bleomycin showed significant increases in total cells as compared to saline treated mice. At 14 and 21 days in bronchoalveolar lavage there were significantly more lymphocytes in bleomycin plus interferon compared to bleomycin plus vehicle mice. In bronchoalveolar lavage, there were usually fewer neutrophils, monocytes and macrophages in bleomycin plus interferon compared to bleomycin plus vehicle mice. Morphometric estimates of the volume of lesion within lung showed no significant differences among the bleomycin treated groups. Stainable collagen fibers were less, but not significantly, in the bleomycin plus interferon compared to bleomycin plus vehicle mice. The number of fibroblasts per volume of lesion was significantly decreased at 14 and 21 days in bleomycin plus interferon compared to bleomycin plus vehicle mice. The total volume of lymphocytes in interstitial lesions was significantly greater at 14 and 21 days in bleomycin plus interferon mice compared to bleomycin plus vehicle mice. These results suggest an inhibitory action of gamma interferon on collagen accumulation and fibroblast proliferation associated with lymphocyte accumulation in the lungs of mice following bleomycin administration.

Animals↗
PubMed1988

Melanosome abnormalities of ocular pigmented epithelial cells in beagle dogs with hereditary tapetal degeneration.

Eyes of laboratory beagle dogs with an inherited tapetal degeneration were abnormally lightly pigmented. The development of pigmentation was followed morphologically from 7 days postnatal to 9 years of age. At all postnatal ages the iris pigmented epithelia contained no normal melanosomes, only organelles resembling secondary lysosomes or residual bodies. The ciliary body pigmented epithelium contained a variety of melanosome organelles at the earliest stages examined, but in fewer numbers than in normal animals. These included premelanosomes, partially melanized and some fully melanized pigment granules. However, the melanin deposition was usually patchy and irregular. With time, many of these granules appeared to condense into residual bodies. The retinal pigmented epithelium in peripheral and inferior posterior regions of affected animals never contained normal appearing melanin granules at any stage of postnatal development. The iris and choroidal stroma had melanosomes of normal size and shape, but many fewer than in normal animals. These results imply that there is local cellular control over melanosome production and regression, since the melanosome abnormalities do not follow the anterior to posterior development of pigment in ocular epithelia. It is proposed that a defect in synthesis of the matrix component of melanosomes could result in absent or abnormal deposition of melanin and initiate a process of autophagy of these organelles.

Animals↗
PubMed1987

Effects of ozone on lung and somatic growth. Pair fed rats after ozone exposure and recovery periods.

Minor differences in lung growth and development during childhood have been considered as a potential cause of rapid decline in pulmonary function in adulthood. Inhalation of ozone commonly causes changes in both body weight and lung volumes, which complicates interpretation of any changes in lung growth. The effects of ozone on lung growth were studied in rats which were pair fed. This technique permitted comparison of ozone-exposed and filtered-air control rats of the same body weight and body size as well as age and sex. Exposure was to filtered air or to 0.64 or 0.96 ppm ozone (UV standard) 8 h/night for 42 nights. A second control group was fed ad libitum and exposed to only filtered air. Half the rats were studied at the end of the 42-night exposures, the rest after a 42-day post-exposure period during which all rats were fed ab libitum and breathed filtered air. Rats examined at the end of the exposure period had larger saline and fixed lung volumes. These larger lungs had greater volumes of parenchyma, alveoli and respiratory bronchioles. Some of these changes persisted throughout a 42-day post-exposure period. Ozone inhalation by young rats alters lung growth and development in ways likely to be detrimental and those changes persist after ozone inhalation stops.

Animals↗
PubMed1987

Impairment in coupled beta-adrenergic receptor and adenylate cyclase system during bleomycin-induced lung fibrosis in hamsters.

The purpose of this study was to evaluate the coupled beta-adrenergic receptor (BAR) and adenylate cyclase (AC) system of the lung during the course of the bleomycin-(Bleo) induced pulmonary fibrosis in hamsters. The BAR population, dissociation constants (Kd), AC activity, and its sensitivity to various stimulators were studied at 2, 4, 7, 14, and 21 days after intratracheal administration of either 1 unit of Bleo or an equivalent volume of saline. The BAR population in the lungs of Bleo-treated animals did not differ from control at the early times, but it was significantly reduced to 5.9 X 10(3) fmol and 3.6 X 10(3) fmol from the control values of 1.1 X 10(4) fmol and 1.5 X 10(4) fmol per lung at 14 and 21 days after treatment, respectively. The Kd values for control hamster lung ranged from 2.5 X 10(-11) M to 3.7 X 10(-11) M, and for Bleo-treated hamster lung, from 2.7 X 10(-11) M to 4.8 X 10(-11) M. The Kd at the earliest time, 2 days after treatment, did not differ significantly from the Kd values at the subsequent times in control, while for Bleo-treated hamster lung, the Kd values at 7, 14, and 21 days were significantly higher than the Kd at 2 days after treatment. The Kd values for Bleo-treated hamster lung were also significantly higher than control at 14 and 21 days. The AC activity of the lung in Bleo-treated hamster was significantly reduced to 67%, 40%, 38%, and 50% of their respective controls in response to H2O (basal), GTP (10(-4) M), GTP + isoproterenol (10(-4) M each), and NaF (10 mM) at 21 days after treatment. The extent of AC stimulation in Bleo-treated hamster lung in response to various stimulators was generally less than that of saline control. Reductions in the BAR population and increased Kd values in Bleo-treated hamster lung were attributed to its fibrogenic ability and not to nutritional deficiency, which may partly be accountable for decreased AC activity of the lung in these animals. However, there were qualitative differences in the lung AC activity between Bleo-treated and nutritionally deprived hamsters, since the enzyme from the latter group was generally more responsive to stimulators than the enzyme from the former group. It was concluded from the findings of this study that an impairment in the coupled BAR and AC system of the lung may be partly responsible for the fibrogenic ability of bleomycin.

Adenylyl Cyclases↗
PubMed1986

Effect of ozone on mean linear intercept in the lung of young beagles.

Although photochemical air pollutants are believed to be associated with respiratory illness, there is also a need to consider their possible effects on postnatal lung maturation. The purpose of this study was to determine whether the maturation of lungs of young beagle dogs might be altered by an inhalation exposure to ozone that represents a severe 5-d episode of photochemical oxidant air pollution. Exposures were at 6 wk of age to purified air, 1 or 2 ppm ozone for 4 h/d on 5 consecutive days. After holding for 6 wk in clean air, lungs were removed and weighed, and the left lung was fixed both by inflation at 30 cm pressure and immersion using buffered formalin. Histologic sections were used for morphometric measurements. Statistical analysis showed that the mean linear intercept (inversely related to lung surface area) was greater than controls (up to about 5%) in the 1 ppm ozone-exposed group. This effect was not seen at 2 ppm ozone, apparently due to large variations in mean linear intercept. No significant differences were seen in body weight, chest girth, lung weight, or volumes of the fixed, inflated lungs. It is concluded that if anatomic maturation of the lung was retarded by this brief regimen of ozone exposure, the effect was small and not likely to have major health consequences.

Animals↗
PubMed1985

Morphology of the distal conducting airways in rhesus monkey lungs.

This study systematically characterizes the organization and nature of epithelial populations in the distal airways of the adult rhesus monkey. Infusion-fixed lungs were evaluated using airway dissection and scanning and transmission electron microscopy. We found that a true bronchiole free of cartilage and alveolar outpockets was not consistently present. Cartilage and alveolar outpocketings were often observed within the same airway generation. The epithelial population of nonalveolarized terminal conducting airways was pseudostratified columnar, consisting of ciliated, mucous, and basal cells. The respiratory bronchiole found immediately distal to the terminal conducting airways had two clearly demarcated zones of distinctly different epithelial populations. Overlying the pulmonary artery was the same pseudostratified ciliated columnar epithelial population observed in nonalveolarized terminal airways. The epithelial population in the remainder of the respiratory bronchiole, not associated with the pulmonary artery, was simple nonciliated cuboidal with a few squamous cells. The cuboidal nonciliated bronchiolar cell differs from the mucous cell by having few small granules and rough and smooth endoplasmic reticulum. The extension of the ciliated, mucous, and basal cells several generations into the respiratory bronchiole in rhesus monkey has not been observed in rodents and other laboratory mammals. Data from studies of human airways, although not explicit, suggest that the rhesus monkey epithelial cell pattern resembles the pattern in the human terminal airways.

Animals↗
PubMed1985

Structural evaluation of the respiratory system.

The theoretical and practical bases for morphological evaluation of the respiratory system useful for inhalation toxicology are reviewed. For most studies we recommend a comprehensive gross examination followed by in vitro tracheal infusion of a fixative containing both glutaraldehyde and formaldehyde in cacodylate buffer. Lungs fixed in this manner are suitable for LM, SEM, and TEM and lung volumes can be determined. The airway orientation of many lesions and the potential for gradients of damage are considered in the lung sampling plan. While LM of paraffin sections continues to be the basic method for evaluation, the SEM and TEM, especially when ancillary methods are used, provide valuable additional information. The use of backscattered electrons and energy-dispersive X-ray analysis in the SEM provides information concerning the localization and elemental analyses of particles. Cytochemical procedures characterize biological activities of specific cell types and are becoming more widely used. Morphometry permits correlation of quantified structure with physiological and biochemical data.

Animals↗