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Biomedical subjects

J D Brain

Publications and source records attributed to J D Brain.

At least 127 records · Page 7Linked to original sources
PubMed1979

Lysosomal enzyme activities in pulmonary macrophages from rabbits breathing iron oxide.

The effects of an in vivo exposure to a nontoxic particle, iron oxide, on lysosomal hydrolases in pulmonary macrophages were examined. Rabbits breathed a submicron-sized aerosol of iron oxide for 3 h (mass concentration, 186 to 222 mg/m3). Macrophages were recovered by lung lavage 0, 12, 18, and 24 h later. The number of cells lavaged after iron oxide was significantly greater than the control number, whereas the amount of protein recovered per 10(8) cells decreased, suggesting the influx of smaller cells. Macrophages from animals exposed to iron oxide reacted histochemically for acid phosphatase showed increased stain intensity and redistribution of enzyme within the cytoplasm. Considerable cell-to-cell variability in enzyme activity was evident in these macrophages. Homogenates of cells exposed to iron oxide assayed for 6 lysosomal acid hydrolases showed little change in specific activity or in total enzyme per 10(8) cells when compared to homogenates of cells from control animals. Sucrose density gradient centrifugation demonstrated that exposure to iron oxide caused an increase in lysosome heterogeneity over that seen in control preparations and the appearance of a population of lysosomes of increased density. An aerosol of iron oxide did not greatly alter the average concentrations of lysosomal enzymes in pulmonary macrophages, but did stimulate recruitment of new cells and thus increases the total amount of some enzymes in the lung.

Acid Phosphatase↗
PubMed1979

Generation and use of three types of iron-oxide aerosol.

Three distinct submicrometric aerosols of iron oxide can be reproducibly generated by combustion of iron pentacarbonyl vapors under varying conditions. Each aerosol was sized with a concentric aerosol spectrometer and was examined with an electron microscope; the specific surface area of each aerosol type was also determined. The "feathers" hematite has a man median aerodynamic diameter (MMAD) of 0.17 micrometer and a large surface area because it is an agglomerate of units 0.005 micrometer in diameter. The "birdshot" hematite has a MMAD of 0.31 micrometer, but has a smaller surface area because the subunits are 0.03 micrometer in diameter. The third aerosol, "gamma-oxide," has a MMAD of 0.73 micrometer and has crystalline subunits 0.2 micrometer in diameter; it is a magnetic form of hematite, gamma-Fe2O3. These aerosols are well suited for studies of deposition and clearance in animal lungs because the particles can be visualized in both light and electron microscopy and can be quantified colorimetrically. The magnetic properties of gamma-Fe2O3 permit enhancement of deposition and noninvasive detection.

Aerosols↗
PubMed1979

Uptake of iron aerosols by mouse airway epithelium.

Spontaneously breathing mice were exposed to an aerosol of iron oxide for 3 hours. Participation of the tracheal and bronchial epithelium in the uptake of iron oxide was noted immediately following the exposure and at 1 day, 4 days, and 7 days postexposure. Observations with the electron microscope revealed that iron oxide was pinocytosed and converted to ferritin and hemosiderin in all epithelial cell types except mucous cells. Iron content increased over time and approximately 50% of the nonmucous cells contained hemosiderin by 4 days postexposure. Ferritin and hemosiderin, but not iron oxide, were noted in connective tissue cells in the submucosa beneath the airway epithelium. Soluble iron and/or ferritin produced in the airway epithelial layer was transported to the submucosa, but normal epithelium prevented the penetration of deposited iron oxide particles to the connective tissue compartment.

Aerosols↗
PubMed1977

Phagocytosis: quantification of rates and intercellular heterogeneity.

We present a method which permits analysis of phagocytic behavior in small samples of macrophages. Both overall phagocytic kinetics and intercellular variability in particle uptake were measured. Macrophages lavaged from Syrian golden hamster lungs were incubated (5 min at 37 degrees C) with 2- to 4-mum plastic particles at 4.6, 6.9, 9.1, and 16.0 X 10(6) part./ml. Harvested macrophages ranged from 0.6 to 4.0 X 10(6) cells per animal. To concentrate the cells and separate them from cell-free substrate after termination of phagocytosis, 30-60% of each flask's contents were centrifuged (400 X g, 20 min) atop a Metrizamide subphase (34% wt/vol, rho = 1.18). Cells were collected from the interface, fixed, and visually scored for number of particles phagocytized. Phagocytic rates followed Michaelis-Menten kinetics with Vmax = 0.63 +/- 0.18 (SEM) part./viable cell per min and Km = 8.5 +/- 2.7 (SEM) X 10(6) part./ml. In every case (23/23 flasks from 6 animals) particle uptake exhibited greater (P less than 0.01) cell-to-cell variability in avidity for substrate than the Poisson distribution would predict from mean number of particles phagocytized per viable cell.

Animals↗
PubMed1977

Lung surface tension and air space dimensions from multiple pressure-volume curves.

Pressure-volume (PV) curves of excised cat, dog, rabbit, and rat lungs were determined in a sequence of three conditions: 1) normal-surface, air-filled; 2) saline-filled; and 3) polyoxyethylene (20) sorbitan monolaurate-(Tween 20) surface, air-filled. Since the surface tension of lung washings containing 2% Tween 20 is constant, the Tween-surface air-filled lungs presumably exhibit the pressure-volume behavior of lungs with constant surface tension. These data along with the assumption of equivalent geometry in the three conditions permit calculation of the variation of surface tension in the normal lung as a function of volume without assuming a specific surface area vs. volume function or a maximum surface tension. The calculated surface tension dropped during deflation from a high of 50 dyn/cm total lung capacity (TLC) to a low of 4 dyn/cm (less than 25% TLC) with the species being roughly similar. The PV behavior of Tween-surface lungs appears to fit a simple model of alveolar expansion. Air dimensions calculated for the four species on the basis of this model are ordered in the same sequence as morphological measurements, but larger in magnitude.

Animals↗
PubMed1977

The respiratory tract and the environment.

The primary determinants of pulmonary disease are environmental. The same thinness and delicacy of the air-blood barrier which allows rapid exchange of oxygen and carbon dioxide also reduce its effectiveness as a barrier to inhaled allergens, carcinogens, toxic particles, and noxious gases, and micro-organisms. Adults breath 10,000 to 20,000 liters of air daily. This volume of air contains potentially hazardous contaminating particles and gases. Future research should explore the diverse physiological mechanisms which prevent the accumulation and deleterious action of inhaled particles and gases. Since most pulmonary diseases are either initiated by or at least aggravated by the inhalagion of particles and gases, the role of environmental factors in the development of respiratory disease is an area worthy of continued support.

Dust↗
PubMed1975

Pathways of clearance in mouse lungs exposed to iron oxide aerosols.

The history of particle clearance was studied in lungs of mice serially sacrificed at intervals up to 14 months following single exposures to an aerosol of submicronic, particulate, iron oxide used as a similitude for atmospheric dust. Clearance was followed by light microscopy in unstained and Prussian blue stained frozen and plastic embedded sections, as well as by electron microscopy, where iron oxide can be recognized by its form. Related problems were investigated through histochemical demonstration of acid phosphatase activity in pulmonary lysosomes and Prussian blue staining of various tissues after administration of iron compounds by gastrointestinal and vascular routes. The iron particles settle extensively but not uniformly on pulmonary alveolar surfaces. Clearance is centripetal and involves two mechanisms, an extracellular mechanism fed by fluid currents sweeping across the surfcace, and cellular mechanism principally involving alveolar macrophages. In the early post exposure period both actively remove deposited particles predominantly through the pulmonary airways. By 24 hours uncleared residues have become ingested and clearance thereafter results mainly from cellular action. Macrophages enter bronchial passages where they sometimes continue to pursue normal activities. A chronic phase of clearance begins when deposited particles become sequestered in macrophages of pulmonary connective tissues. These cells are reached by several routes, not least by crossing the bronchial epithelium. Particle clearance from these macrophages is very slow, and residue-containg cells eventually congregate in lymphoid tissues surrounding major bronchi. These findings are discussed as they help to develop an overall picture of clearance from the lungs and as they bear on related topics, such as functional roles of alveolar and pulmonary connective tissue macrophages and the pathogenesis of chronic bronchial disease.

Acid Phosphatase↗
PubMed1975

Species differences in aerosol deposition.

A theory for scaling the collection efficiency of the lung and respiratory tract is developed by identifying the dimensionless groups of variables controlling the deposition of an inhaled aerosol. The theory predicts that collection efficiency is substantially independent of body size under physiologically equivalent conditions. Thus, total deposition depends primarily on differences in ventilation per gram body weight. Experiments on mice, hamsters, rats, rabbits and dogs simultaneously exposed to the same 198Au labelled 0.78 micron aerosol are in agreement with this prediction, but show wide variability of collection efficiency even in animals of nearly identical size.

Aerosols↗
PubMed1975

The effect of increased particles on the endocytosis of radiocolloids by pulmonary macrophages in vivo: competitive and toxic effects.

We have developed a technique for measuring the rate of particle ingestion by pulmonary macrophages in vivo. This technique has been used to examine the impact of pre-exposure to ferric oxide, colloidal carbon, and coal dust on the endocytosis of a test particle, colloidal gold. Our technique for estimating endocytosis is as follows: Syrian golden hamsters received intratracheal instillations (0.15 cm3/100 g body weight) of a suspension of colloidal 198Au (approximately 30 nm diameter). Two hours following instillation, each hamster was sacrificed and its trachea cannulated. The lungs were lavaged 12 times with saline solutions, and the number of cells and gold particles in each wash determined. Analysis of the washout curves permits the calculation of the fraction, gamma, of the colloidal particles which has been ingested at a time, t. This method was then used to measure the influence of inhaled or intratracheally instilled particles on the endocytosis of the gold particles. Hamsters breathed ferric oxide aerosol spontaneously or were given intratracheal instillations of colloidal carbon or coal dust. Immediately following the exposure, the ability of the macrophages to ingest a test particle was assayed by the technique described above. In all instances, colloidal gold endocytosis measured at 2 h was significantly depressed. However, when challenged by the gold colloid 24 h after exposure to the inhaled or instilled particles, only the coal dust group exhibited depressed endocytosis. We conclude that all dusts studied competitively inhibit endocytosis, but only some exhibit a toxic effect on macrophage function.

Aerosols↗