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J D Brain

Publications and source records attributed to J D Brain.

At least 109 records · Page 6Linked to original sources
PubMed1982

Breathing patterns influence aerosol deposition sites in excised dog lungs.

Particles' suspended in inhaled air can deposit on lung surfaces. The amount deposited in different lung regions is determined by distribution of ventilation and local efficiency of particle collection. We examined how the pattern of ventilation influences sites of aerosol deposition in excised dog lungs. The lungs breathed a 99mTc-labeled aerosol according to one of three patterns: slow-deep (f less than 25/min, VT greater than 0.35 TLC); rapid-shallow (f greater than 65/min, VT less than 0.26 TLC); and slow-shallow (f = 8.4/min, VT = 0.1 TLC). After exposure, lungs were inflated, dried, and sliced transversely at 1-cm intervals. Distribution of deposited aerosol in each slice was measured by 1) gamma camera, 2) autoradiography, and 3) dissection of each slice into pieces whose activity, weight, and airway content were recorded. Our results indicate that a) total deposition decreases as f increases, b) slow-deep breathing produces uniform deposition throughout the lung, but with little aerosol collection in large airways, c) rapid-shallow ventilation results in enhanced large-airway deposition and marked heterogeneity in deposition distribution, and d) slow-shallow breathing enhances small-airway deposition. The deposition distributions characteristic of different breathing patterns were apparent on the visual displays from the gamma camera and autoradiographs. These techniques showed particle retention changing across lobar divisions, as a function of distance from the hilum, and across the lungs in both the caudal-to-cranial and dorsal-to-ventral directions.

Aerosols↗
PubMed1982

Deposition and clearance of inhaled aerosol in the respiratory tract of chickens.

Sixteen unanesthetized adult White Leghorn chickens (Gallus domesticus) were exposed to an aerosol of 99mTc-labeled submicrometric particles and killed 0, 1, 12, or 36 h later. The amount and distribution of radioactive particles retained in the lungs and skeletal system were measured to describe regional deposition and clearance. Particles were present in the lungs, air sacs, and skeletal system immediately after exposure. Reduction in activity with time suggested clearance of aerosol from the lungs and pneumatized bones. Aerosol particles were not distributed uniformly within the lungs; there was greater retention in the caudal regions. No dorsoventral gradients were observed. Of the initial lung deposition, 54 +/- 13.9% (SD) remained 1 h postexposure and 35.6 +/- 20.9% remained 36 h later. These data suggest an early fast phase of lung clearance followed by a slower phase. Detailed morphological studies are needed to understand the underlying clearance mechanisms and the bases for the differences in regional deposition.

Aerosols↗
PubMed1982

Murine cytomegalovirus pneumonia. Description of a model and investigation of pathogenesis.

Pneumonitis was produced in CD-1 mice by intratracheal instillation of murine cytomegalovirus. Lethal pneumonia occurred after instillation of virus derived from partially purified salivary gland homogenates, whereas virus attenuated by serial passage in cell culture caused mild disease and no mortality, even though both virulent and attenuated strains achieved comparable peak titers in lung homogenates. Virulence was characterized by rapid association of virus with pulmonary macrophages and early spread of virus from macrophages to susceptible parenchymal cells. This resulted in enhanced viral growth and cellular destruction during the first 5 days of infection. Delay in the early growth of murine cytomegalovirus in pulmonary parenchyma may diminish the destructive effects of virus on the lung and prevent mortality.

Animals↗
PubMed1982

Potentiation of bleomycin-induced lung injury by exposure to 70% oxygen. Morphologic assessment.

The effects of a single intratracheal instillation of bleomycin followed by exposure to 70% oxygen for 72 h were studied in hamsters. Mortality increased markedly among hamsters exposed to 70% oxygen for 72 h after bleomycin instillation, compared with animals receiving bleomycin and breathing room air. The lethal dose required to kill 50% of the hamsters at 30 days (LD50, 30 day) for bleomycin alone was 0.73 U/100 g body weight, whereas the LD50, 30 day for bleomycin followed by 70% oxygen fell to 0.23 U/100 g body weight. Using morphometry and light microscopy, we found that the amount of diseased lung increased in hamsters given bleomycin with hyperoxia compared with that in those treated with bleomycin alone. After 0.20 U bleomycin and air, 2.8 +/- 1.6% of the lung was abnormal, but with 0.20 U bleomycin followed by 70% oxygen, 42.7 +/- 17.9% of the lung was abnormal. At bleomycin doses that produced no apparent lesions, the addition of 70% oxygen for 72 h produced focal interstitial fibrosis at 30 days. Neither mortality nor significant histologic changes were seen in hamsters treated with saline followed by exposure to 70% oxygen for 72 h. This study demonstrates that hyperoxia potentiates bleomycin damage and suggests that the use of elevated oxygen concentrations in patients being treated with bleomycin should be minimized.

Air↗
PubMed1981

Effects of colchicine or cytochalasin B on pulmonary macrophage endocytosis in vivo.

Pulmonary macrophages defend lung surfaces by ingesting deposited particles. We investigated to what extent this uptake of particles can be modulated in vivo by two drugs, colchicine and cytochalasin B (CytB). 198Au colloidal gold, in isotonic saline carrier fluid, was intratracheally instilled into male Syrian golden hamsters. The uptake of these particles by pulmonary macrophages was measured when the carrier fluid contained only colloidal gold and when this test particle was combined with graded doses of either drug. We found that macrophage uptake of the particles 1 h after instillation was depressed 37% when colchicine was added to the instillate (150 micrograms/100 g BW). Depression of particle uptake was also seen with CytB at 15 micrograms/100 g BW. Experiments with tritiated colchicine and CytB showed that both drugs were rapidly cleared from the lungs early in the 1 h phagocytic period. The effect of intravenous colchicine and CytB on the clearance of intravenously injected gold colloid by the liver and spleen reticuloendothelial system was negligible. The results of these experiments, in conjunction with in vitro effects of colchicine and CytB, provide insight into the components of cell function active in particle uptake in situ.

Animals↗
PubMed1981

Pulmonary defense mechanisms in Boa constrictor.

We studied aerosol deposition and the response to inhaled particles and irritants in lungs of Boa constrictor. Snakes which breathed submicrometric particles radiolabeled with 99mTc retained 41.4 +/- 9.9% of the aerosol in the trachea, 42.5 +/- 8.8% in the anterior faveolar regions, and 8.7 +/- 4.1% in the posterior saccular regions of the lungs. Low activity recovered in the gastrointestinal tract over a 5-h period following aerosol exposure indicated slow clearance of inhaled particles. In contrast to mammalian lungs, there are no macrophages resident on the surface of boa lungs, and uningested particles persist for up to 4 days without being phagocytized. Particles and irritant stimuli (Fe2O3, endotoxin, and N-formylmethionylphenylalanine) elicited only eosinophilic granulocytes that were not phagocytic. The numbers of these cells peaked at 24 h following exposure and declined gradually over the next 7 days. Lavage fluid from stimulated snake lungs contained many large lamellar figures continuous with tubular myelin, a form of surfactant. Very little of this material was recovered from control lungs. Response to inhaled particles and lung injury in boas increased surfactant release, elicited eosinophilic granulocytes, but did not recruit phagocytic mononuclear cells.

Animals↗
PubMed1981

Steady expiratory flow in dog lungs: an isovolume preparation.

By supplying air and other gases through discs glued to the pleural surface, we studied steady expiratory flow at constant volume. Dog lungs were studied at constant PA - Ppl (alveolar minus pleural pressure) of 7 to 10 cmH2O, as increasing flow was achieved by increasing driving pressure [Ppl - Pao (airway opening pressure)]. Flow became limited (independent of further increases in Ppl - Pao) at between 3.5 and 5.5 l/s. Isovolume-pressure-flow (IVPF) curves constructed from forced expirations at graded efforts yielded similar maximal flows. When the airways were made rigid by drying, flow limitation was abolished. When various gases were passed through the dried lung Moody plots of normalized pressure drop (CD) vs. Reynolds number (Re) showed that all of the data could be plotted on a single curve. Although variable among animals, all Moody plots showed a laminar flow region at Re below 100 and an inertial region at Re above 10,000, with a distinct transition.

Animals↗
PubMed1981

The pulmonary toxicity of an ash sample from the MT. St. Helens Volcano.

Volcanic ash was collected from the Moses Lake region of Washington State after the 18 May 1980 eruption of Mt. St. Helens. The ash was tested in a short-term bioassay system using hamsters exposed by intratracheal instillation. One day after exposure the lungs were lavaged and the fluid collected was characterized using several parameters that represent different manifestations of lung injury: (a) in situ phagocytic ability of pulmonary macrophages; (b) the inflammatory response, as shown by polymorphonuclear neutrophil numbers and albumin levels in lung lavage fluid; and (c) release of cytoplasmic and lysosomal enzymes into the cell-free supernatant of lung-lavage fluid. The response to volcanic ash was elevated compared to controls, but was similar to the response to Al2O3, a dust considered to be relatively inert. In contrast, the response to alpha-quartz, a highly toxic fibrogenic dust, was significantly greater than the response to either volcanic ash or Al2O3 for most parameters measured.

Air Pollutants↗
PubMed1980

Macrophage damage in relation to the pathogenesis of lung diseases.

Pulmonary macrophages are important since their migratory patterns and behavior are often pivotal events in the pathogenesis of pulmonary disease. Alveolar macrophages act to decrease the probability of particle penetration through epithelial barriers, and their phagocytic and lytic potentials provide most of the known bactericadal properties of the lung. Macrophages are also involved in immune responses and in defense against neoplasms. Increased inert or infectious particles stimulate the recruitment of additional macrophages. Most free cells containing particles eventually reach the airways and are quickly carried to the pharynx and swallowed. In addition, evidence has now accumulated that macrophages play a part in the pathogenesis of pulmonary diseases. For example, the ingestion of some particles by macrophages causes a release of lysosomal enzymes into the macrophage cytoplasm. These enzymes may kill the macrophage, and dead or dying macrophages release a substance with attracts fibroblasts that elicit fibrogenic responses. Other toxic particles, such as cigarette smoke, my lead to a release of proteases and other toxic enzymes. All particles are capable of competitive inhibition of phagocytosis in macrophages and many may be cytotoxic and further depress phagocytosis. In addition, connective tissue macrophages may contribute to lung disease by concentrating and storing potent carcinogens or other toxic particles close to a reactive bronchial epithelium for long periods. Thus, even through macrophages serve as a first line of defense for the alveolar surface, they may also be capable of injuring the host while exercising their defensive role.

Air Pollutants↗
PubMed1980

The effect of SO2 on the uptake of particles by mouse bronchial epithelium.

In three experiments, we have explored the uptake and transport of colloidal gold (Au) and iron oxide (Fe2O3) by normal and SO2-injured bronchial epithelium. In the first experiment, mice were exposed to a 2-hr aerosol of Au; in the second experiment, mice were exposed to SO2 (250 ppm) for 3 hr, then to Au; and in the third experiment, mice inhaled SO2 and then were exposed to Fe2O3. In each experiment, animals were killed at 0 hr, 1 day, and 4 days postexposure. From each animal, samples of large airways were examined by electron microscopy, and the cell type and particle location were recorded. Au was not readily taken up by the bronchial epithelium in that only two cells out of 1162 contained particles. No Au was seen in the submucosa. Exposure to SO2 produced a mild, but nonnecrotic response characterized by an increase in mucus, vacuolated cells, detached cilia, and an influx of polymorphonuclear leukocytes. SO2 did not affect the uptake of Au; 2 out of 1177 epithelial cells contained Au. However, gold did reach the submucosa. Results from the SO2 plus Fe2O3 experiment were compared to a previous study of similar design in which mice were exposed only to Fe2O3. SO2 increased the uptake of iron and affected the distribution of intracellular iron among the different cell types. It is possible that increased iron uptake is due to either injury or to changes in particle solubility produced by the SO2.

Aerosols↗
PubMed1979

Smoking impairs long-term dust clearance from the lung.

The time for the long-term clearance of dust from human lungs was measured. Three heavy cigarette smokers and nine nonsmokers inhaled a harmless trace amount of magnetic dust, Fe3O4. From periodic measurements with a sensitive magnetic detector of the amount of this dust remaining in the lungs, a clearance curve was determined for each subject. This magnetic tracer method allows clearance to be safely followed for a much longer time than with radioactive tracer methods. The dust clearance in the smokers is considerably slower than in the nonsmokers. After about a year, 50 percent of the dust originally deposited remained in the lungs of the smokers whereas only 10 percent remained in the lungs of the nonsmokers. The smokers therefore retained five times more dust than the nonsmokers. This impaired clearance of Fe3O4 suggests impaired clearance in smokers of other dusts, such as toxic occupational and urban dusts. The higher retention of these dusts may contribute to the higher incidence of lung diseases in smokers.

Adult↗