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Biomedical subjects

G S Davis

Publications and source records attributed to G S Davis.

At least 73 records · Page 4Linked to original sources

Morphologic changes induced by photoperiod in eyes of turkey poults.

Large White commercial tom poults were grown from 1 day to 8 weeks of age in the following light treatments: (i) continuous incandescent light (24LL); (ii) 23 hours of incandescent light and 1 hour of darkness/day (23L:1D); (iii) 12 hours of incandescent light and 12 hours of darkness/day (12L:12D); or (iv) natural decreasing day lengths (natural). At 8 weeks of age, significant (P less than 0.05) morphologic changes in eyes occurred. Poults exposed to the 24LL or 23L:1D had heavier eyes than did poults exposed to the 12L:12D or natural day length. In addition, the eye size (anterior to posterior diameter and horizontal width) exposed to the 24LL treatment was greater than those exposed to 23L:1D, 12L:12D, or natural day length. Cornea heights of poults exposed to 24LL or 23L:1D were smaller than cornea heights of those exposed to 12L:12D or natural day length. Marked differences did not occur in intraocular pressure among treatments.

Animals↗

Mineral dust and cell recovery from the bronchoalveolar lavage of healthy Vermont granite workers.

We characterized the bronchoalveolar lavage (BAL) from healthy Vermont granite workers to investigate the pulmonary response to a chronic exposure to an injurious agent. Nine granite workers with 4 to 36 yr of employment in the industry and 27 unexposed volunteers were normal by history, physical examination, electrocardiogram, blood count, spirometry, and chest radiograph. Lavage cell recovery and percent neutrophils were not different. Lymphocyte recovery in BAL was increased in the granite-exposed population. Granite dust was present within the majority of alveolar macrophages from granite workers compared with those from control subjects, as determined by polarizing light microscopy and confirmed by scanning electron microscopy with X-ray energy spectrometry. There were no differences in phagocytic function or viability of macrophages from granite workers compared with those from unexposed volunteers. We conclude that in exposed populations, granite dust can be detected and semiquantitated in lavage specimens within the alveolar macrophages, macrophage function is preserved, and the response to this exposure involves an influx of lymphocytes.

Adult↗

The effect of light duration on turkey poult performance and adrenal function.

Day-old tom poults were exposed to one of the following light treatments: 1) continuous incandescent light (24LL), 2) 23L:1D incandescent light, 3) 12L:12D incandescent light, or 4) natural day lengths only. Mortality was recorded daily. At Weeks 1, 2, 4, 6, and 8, after poult placement, body weights and feed consumption were measured. At each of these times, 10 poults were sacrificed from each treatment group for evaluation of plasma corticosterone. Day lengths utilized in this study had no consistent effect on poult-performance parameters except from 0 to 2 weeks of age. During this time, poults in the 24LL and 23L:1D treatments consumed less feed but were similar in body weight to poults in the other treatments. Adrenal function was also not consistently affected by day length. However, in all treatment groups plasma corticosterone was lowest during the first 2 weeks posthatching, when compared to hormone levels at 4, 6, and 8 weeks. The lower corticosterone that occurred during the first 2 weeks posthatching may be involved in early poult mortality.

Adrenal Cortex↗

Adrenal cortical response of tom poults.

In each of two trials, plasma corticosterone (B) was measured in Large White turkey tom poults after the following treatments were applied: 1) .9% saline injected; 2) cold water immersion, and 3) adrenocorticotropic hormone (ACTH) injected (10 IU/kg body weight). Poults were treated at 3- to 4-day intervals from the day of hatching to 21 days of age. Plasma samples were obtained at 1, 2, 3, 4, and 6 hr posttreatment. In both trials, there was a depression in B levels within the first 3 hr following ACTH or cold water immersion treatment. Significant increases in plasma B levels of the cold water treatment occurred at 4 hr posttreatment in Trial 1 in 7-day-old poults and in Trial 2 in 21-day-old poults. A significant adrenal cortical response to ACTH injection was observed in 3- and 7-day-old poults at 6 hrs posttreatment in Trial 2. Plasma B concentrations were also measured in three groups of nontreated Large White tom poults on the day of hatching at a commercial hatchery. Plasma samples were obtained from poults in incubators at 1000 hr, immediately following commercial processing procedures at 1030 hr, and at poult placement at 1330 hr. Plasma B levels of poults sampled in the incubator and after processing were similar. However, B levels of poults sampled at placement were increased significantly above the other two groups.

Adrenal Cortex↗

Variable tracheal stenosis related to body position.

We demonstrated a variable extrathoracic tracheal stenosis which developed after technically adequate tracheostomy and was worsened by changes in body position. When the patient's arms were above his head, minimal airway diameter was reduced 31 percent, and maximal inspiratory flow rate 37 percent below values measured with arms down, but expiratory flow rates were preserved. Tracheostomy may disrupt the integrity of tracheal support and allow airway collapse under circumstances of increased extratracheal or decreased intratracheal pressure.

Forced Expiratory Flow Rates↗

The kinetics of early inflammatory events during experimental pneumonia due to Legionella pneumophila in guinea pigs.

An animal model of Legionella pneumophila pneumonia was developed to study aerosol infection, pathogenesis, and pulmonary host defense mechanisms. Guinea pigs were exposed in an inhalation facility that limited the aerosol of L pneumophila to the snout. Bronchoalveolar lavage was used to sample airspace cells, secretions, and bacteria during developing infection in 79 exposed animals and 13 uninfected controls. An influx of polymorphonuclear neutrophils followed exponential bacterial growth during the initial three days of infection and coincided with limitation of the increase in bacteria recovered. A macrophage influx occurred at three to five days. Bacteria were eliminated from the lung by 11 days after exposure. Albumin in lavage fluid peaked at two days. Most viable L pneumophila organisms were associated with alveolar macrophages, whereas most of the bacteria associated with polymorphonuclear neutrophils were nonviable. Recruited, and possibly immune, defenses appear to be required for successful resolution of legionella pneumonia.

Animals↗

Effect of alveolar lining material-coated silica on rat alveolar macrophages.

The disparity between in vitro silica cytotoxicity toward macrophages and their in vivo resistance to injury following inhalation of silica at physiologic concentrations is unresolved. It is probable that inhaled silica particles absorb a variety of biological substances including proteins and alveolar lining material (ALM) thus altering the in vivo response of the macrophage to these particles. Silica (SI) particles coated with rat ALM and uncoated SI particles were studied for their ability to injure rat alveolar macrophages (AM) in vitro. Suspensions of particles were tested at concentrations from 0 to 400 micrograms per 2 X 10(6) cells. Cytotoxicity was assessed by the percent of total cellular lactate dehydrogenase (LDH) released by AM into the culture medium during incubation. Comparable physical association by ALM-coated and uncoated SI particles with AM was shown by scanning electron microscopy combined with X-ray energy spectrometry. These data show that SI coated with ALM is effectively phagocytosed by AM in vitro but is much less cytotoxic than uncoated SI. The surfactant lipids which presumably coat inhaled SI particles in the lung may reduce or delay their toxicity for AM.

Animals↗

Protein and antibody in lavage fluid of guinea pigs with Legionella pneumophila pneumonia.

Guinea pigs were infected in an inhalation facility that limited an aerosol of L. pneumophila to the snout, as previously reported in detail (Davis et al., 1982). Individual animals were sacrificed for study either immediately after exposure, at 16 hours, at days one through seven, or at 11 days. Bronchoalveolar lavage was carried out to obtain fluid to study the following: total protein, albumin and immunoglobulin G (IgG) concentrations, and the titer of antibody to L. pneumophila. Antibody also was measured in serum obtained at the time of sacrifice. Concentrations of total protein, albumin, and IgG in lavage fluids peaked 2 days after exposure and correlated with the appearance of maximal numbers of polymorphonuclear cells in the lungs. Presumably, this increased protein resulted from exudation of serum across the alveolar-capillary membrane, which loses its integrity secondary to pneumonia. However, the ratio of IgG/albumin was elevated in animals studied 11 days after exposure even though the concentration of albumin was normal by this time. One possible explanation for this observation is that IgG was being produced in the lung. Antibody in lavage fluid was detected 7, and 11 days post-exposure, and might be important in the recovery of guinea pigs from this infection.

Albumins↗

Lavage type III procollagen N-terminal peptides in human pulmonary fibrosis and sarcoidosis.

Levels of type III procollagen N-terminal peptide were immunoassayed in sera and bronchoalveolar lavage fluids from healthy volunteers and patients with idiopathic pulmonary fibrosis or sarcoidosis. Peptide levels normalized to protein were higher than corresponding serum levels in all groups, suggesting that the lung is a producer of this peptide. Levels were significantly elevated in both patient groups, suggesting increased rates of type III collagen synthesis. Values were highest in idiopathic pulmonary fibrosis samples. Correlation of peptide levels with clinical severity of disease and lavage cell profiles was poor, perhaps because the latter reflects aspects of the disease process other than that stage in which type III collagen synthesis is altered. Lavage analyses of procollagen peptides may provide an important index of altered collagen synthesis in interstitial lung disease.

Amino Acid Sequence↗

Mineral dusts as etiologic agents in pulmonary fibrosis: the diagnostic role of analytical scanning electron microscopy.

This report demonstrates the value of analytical scanning electron microscopy (SEM) in the evaluation of patients with fibrosing pulmonary disease. We describe the findings in six illustrative cases in which prebiopsy or premortem clinical and epidemiologic information did not suggest an etiologic association with exposure to fibrogenic dusts. Exogenous materials were inconstantly recognized by polarized light microscopy, but examination by SEM resulted in localization of significant inorganic deposits in the biopsy and autopsy tissues studied. Talc, mica, graphite, and mixed inorganic dusts were found in these six cases. Characterization of this material by SEM morphology and x-ray energy spectrometry provided the basis for re-appraisal of the exposure history and its potential pathogenetic importance. The technics described utilize routinely processed, paraffin-embedded tissue, and are readily applicable to problems encountered in the hospital setting.

Adult↗

Analyses of sequential bronchoalveolar lavage samples from healthy human volunteers.

Subsegmental bronchoalveolar lavage of human subjects provides an accessible sample of cells and secretions from the lower respiratory tract for clinical and research study. Technical factors that may modify lavage results have received little attention. The effects of lavage volume on the patterns of recovered cells and biochemical components were studied by separately analyzing each of 4 sequential 60-ml syringes of saline instilled into a subsegment of the right middle lobe. Fourteen healthy normal subjects volunteered for lavage. Recovery of cells from both nonsmokers and smokers increased and then remained essentially constant in subsequent syringes, suggesting elution of adherent macrophages from the alveolar surface. Protein, carbohydrate, lipid, and potassium appeared in decreasing concentrations in sequential syringes, but different constituents followed separate patterns. Simple mixing models do not explain the observed results. Measured values for the components in a "small" 120-ml lavage may be substantially different from the values in a "large" 240-ml lavage. Further study of the kinetics of recovery of selected lavage components may provide better understanding of the origins and functions of these substances in the lung.

Adolescent↗

Legionnaires' pneumonia after aerosol exposure in guinea pigs and rats.

We developed an animal model of Legionnaires' pneumonia to permit study of aerosol infection, pathogenesis, and pulmonary host defense mechanisms in this disease. Guinea pigs and rats were exposed in a nose-only inhalation facility for 30 min to an aerosol of Burlington serogroup 1 Legionella pneumophila. Lungs contained 10(3) to 10(4) L. pneumophila immediately after exposure. Both guinea pigs and rats developed pneumonia, with 100% infectivity by microbiologic, histologic, and serologic criteria. Guinea pigs demonstrated illness, fever, and 56% mortality; rats showed little illness and 11% mortality. In both species, diffuse patchy pneumonitis coalesced and consolidated as the disease progressed. Aerosol challenge with 3H-L. pneumophila showed exponential growth of the bacteria in the lungs of both species. Guinea pigs and rats can be infected by aerosol exposure to L. pneumophila to produce a disease that closely simulates human Legionnaires' pneumonia. Rapid initial intrapulmonary growth suggests that resident lung defense mechanisms are quite ineffective against L. pneumophila, and that recruited or immunospecific defenses may be more critical in the outcome of infection. The difference in severity of illness between guinea pigs and rats may be exploited for different experimental designs.

Aerosols↗

Deposition and translocation of inhaled silica in rats. Quantification of particle distribution, macrophage participation, and function.

Chronic exposure to silica dust causes fibrotic lung disease. Using brief exposures, we have attempted to define the initial patterns of dust deposition, anatomical compartments through which silica is translocated, and the participation of pulmonary macrophages in clearing the inhaled dust. To accomplish this, particle distribution and translocation at the alveolar level were studied in rats exposed to aerosolized alpha-quartz. Animals were exposed to 109 mg. per cu. m. of crystalline silica in inhalation chambers for 3 hours and sacrificed at varying times after exposure. The lungs were fixed by vascular perfusion through the right ventricle and tissue blocks were prepared for transmission and scanning electron microscopy. Lungs of additional animals were lavaged to recover populations of pulmonary macrophages for in vitro studies. Scanning electron microscopy in concert with back-scattered electron imaging showed that 24 hours postexposure there was a significant decrease in the number of silica particles per unit area of alveolar duct surface when compared with lung tissue from animals sacrificed immediately after exposure. Transmission electron microscopy revealed that silica crystals had been translocated to alveolar type I cells, interstitium, and macrophages. The percentage of silica-containing macrophages on alveolar surfaces increased from 36 +/- 2 per cent (mean +/- S.E.) immediately after exposure to 66 +/- 2 per cent during the 24 hours following exposure. This high percentage of macrophage participation was maintained through a 24-day postexposure period and then returned to 25 +/- 2 per cent 42 days after exposure. The percentage of silica-containing macrophages recovered by lavage were remarkably similar to those studied in situ: 24 +/- 4 per cent immediately postexposure, 62 +/- 3 per cent from 12 hours through 24 days, and 28 +/- 4 per cent 42 days postexposure. Although the percentage of macrophages with silica remained steady, the amount of silica per cell decreased during this 12-hour to 24-day period. Metabolic and viability studies of lavaged macrophages in vitro showed no differences between sham and silica-exposed animals. We propose that the events reported here represent normal, steady state clearance of a subpathogenic dose of potentially toxic particulates.

Animals↗

Legionnaires' pneumonia after intratracheal inoculation of guinea pigs and rats.

We have developed a model of legionnaires' pneumonia in guinea pigs and rats. A reproducible population of Legionella pneumophila was obtained in late exponential growth phase and inoculated into the trachea of young animals. Either immunologic or microbiologic evidence of infection was demonstrated in 27 or 28 guinea pigs and 19 of 20 rats that had been inoculated with 10(5) to 10(7) colony-forming units. An acute pneumonia that resembled human legionnaires' disease was produced in both species, and Legionella antigen was closely related to inflammation in the distal air spaces. A fatal illness was produced in guinea pigs, and pneumonia was more extensive than in rats. Extrapulmonary inflammatory lesions, particularly splenic necrosis, were more frequent in guinea pigs than in rats. Each rodent species has potential advantages for testing specific questions and both should be useful for future investigations.

Animals↗

Pulmonary macrophages alter the collagen phenotype of lung fibroblasts.

Cultured lung fibroblasts produced and secreted interstitial collagen types I and III. The relative proportion of type III collagen increased as a linear function of cell density, with confluent cultures producing 8.6% type III collagen. When human lung fibroblasts were cultured in the presence of newly harvested lung macrophages, the proportion of type III collagen secreted rose to 15.5%. This high level of type III collagen synthesis was greater than could be induced by withdrawal of serum, a perturbation known to alter the proportion of types I and III collagen synthesized by fibroblasts. This effect on fibroblast phenotype was independent of cell density, as both low and high density cultures of fibroblasts responded similarly when cultured with macrophages. There was no evidence that fibroblasts synthesize new or different collagen types (such as type I trimer) in response to macrophages. Optimal conditions for eliciting an effect on fibroblast connective tissue metabolism required interaction of the two cell types for 5-8 days. These in vitro changes are analogous to the sequence of interactions and changes in connective tissue metabolism seen during recovery from tissue injury.

Cell Communication↗