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Biomedical subjects

P Gehr

Publications and source records attributed to P Gehr.

At least 55 records · Page 3Linked to original sources
PubMed1987

Accumulation of anthracotic particles along lymphatics of the human lung: relevance to "hot spot" formation after inhalation of poorly soluble radionuclides.

Large lung sections of humans of advanced adult age revealed a markedly nonuniform retention pattern of dense anthracotic particle aggregates, with an impressive accumulation of this material along pulmonary lymphatics, i.e. the deep (peribronchial), septal (perivenous) and superficial (pleural) networks. Conversely, the alveolar parenchyme contained only occasional, small aggregates of macrophages heavily loaded with carbon, representing little more than 2% of this material in lung tissue. Although translocation kinetics of anthracotic particles cannot readily be compared to those of highly toxic alpha-emitting, poorly soluble radionuclides such as 239PuO2, lymphatic drainage of the latter over the years may also be expected to lead to a concentration of radioactive material along lymph vessels. Since human data on the effects of inhaled 239PuO2 are virtually lacking, the above distribution pattern is apt to help in identifying cells and other tissue components most heavily at risk. Findings are also relevant to the problem of "hot spot" formation in vivo and its possible sequelae. The latter are briefly discussed with regard to both stochastic and non-stochastic effects.

Cell Aggregation↗
PubMed1987

The postnatal development and growth of the human lung. I. Morphometry.

The lungs of 7 children (age: 26 days to 5 years 4 months) who died from non-respiratory causes were morphometrically investigated by means of light and electron microscopy. For analysis, the set of data was supplemented with results obtained previously on 8 normal adult lungs using similar quantitative techniques (Gehr et al., 1978). The results allowed us to distinguish two phases of postnatal lung development and growth, the first phase lasting from birth to about 18 months and the second phase from then to adulthood. The first phase was characterized by an overproportionate volume increase in the O2-transporting media, air and blood, at the expense of the parenchymal tissue compartment. In the second phase, the volumetric composition of the lung did not change further because there was proportionate growth of all lung compartments. The growth curves for the airspace and capillary surface areas were not biphasic: they increased in direct proportion to lung volume from birth to adulthood, indicating a steady increase in the air-blood interface complexity during the entire growth period. As a consequence of the differences in growth paces between the various structural lung components in early childhood, the morphometric parameters showed large variations in their overall growth rates between birth and adulthood. Thus, the parenchymal tissue components increased by a factor of 15, lung volume and the gas-exchange surface areas between 20 and 25 times (in parallel to body mass), and, finally, the O2-transporting media, air and blood, more than 30 times. The morphometrically determined pulmonary diffusing capacity for O2 (DLO2) scaled with body mass to the power of 1.15, a value significantly different from 1. This relative improvement with age of the gas exchange function per unit body mass is due mainly to an overproportionate growth of the capillary blood compartment.

Adult↗
PubMed1985

Transfer effects in endurance exercise. Adaptations in trained and untrained muscles.

The effects of 8 weeks of bicycle endurance training (5 X /week for 30 min) on maximal oxygen uptake capacity (VO2max) during arm and leg ergometry, and on the ultrastructure of an untrained arm muscle (m. deltoideus), and a trained leg muscle (m. vastus lateralis) were studied. With the training, leg-VO2max for bicycling increased by +13%, while the capillary per fiber ratio and the volume density of mitochondria in m. vastus lateralis increased by +15% and +40%, respectively. In contrast, the untrained m. deltoideus showed an unchanged capillary per fiber ratio and a decreased mitochondrial volume density (-17%). Despite this decrease of mitochondrial volume arm-VO2max increased by +9%. It seems unlikely that the observed discrepancy can be explained by cardiovascular adaptations, since arm cranking did not fully tax the cardiovascular system (arm-VO2max/leg-VO2max: 0.74 and 0.71 before and after training, respectively). Thus neither cardiovascular adaptations nor local structural changes in the untrained muscles could explain the increased arm-VO2max. However, the enhanced capacity for lactate clearance after endurance training could be sufficient to account for the larger VO2max during arm cranking. We propose that an increased net oxidation of lactate might be responsible for the increased arm-VO2max found after bicycle endurance training.

Adult↗
PubMed1985

Lung fixation by airway instillation: effects on capillary hematocrit.

Instillation of glutaraldehyde into the airways of collapsed lungs is a widely used fixation procedure for analysis of pulmonary structure-function relations. In order to better define the effect of this fixation method on the pulmonary microvasculature, a morphometric analysis was made in rat lungs fixed under different conditions. In one group of animals the lungs were allowed to collapse; then the circulation was suddenly interrupted with a sling placed in the coronary sulcus before instillation of the fixative. In a second group the same procedure was carried out with the exception that the lungs were kept inflated at the time of circulatory arrest. In third group the standard technique was used, i.e., the collapsed lungs were instilled before circulatory arrest. The results show that important parameters of alveolar and septal dimensions, and in particular the capillary surfaces and volumes, are alike regardless of the procedure of fixation. However, in lungs fixed by the standard technique a higher capillary hematocrit (approximately 33%) and a decreased harmonic mean thickness of the plasma barrier were found. This artificial hemoconcentration in the microvasculature resulted in a substantial morphometric overestimate of the diffusing capacity of the lung.

Animals↗
PubMed1984

Noninvasive studies of Kupffer cells in situ by magnetometry.

Magnetic iron oxide (gamma-Fe2O3) particles were injected intravenously into four male New Zealand white rabbits. Most of these particles were phagocytized by the Kupffer cells. When the animal was placed in a magnetic field, the particles in the liver became magnetized and aligned. After removal of the external magnetizing field, the particles collectively produced a remanent magnetic field which was measured at the body surface. The strength of this field was proportional to the amount of magnetic particles present in the liver; sequential measurements thus allowed us to describe their disappearance from the liver. After each magnetization, the remanent field rapidly decayed due to particle rotation (relaxation). Since the particles were confined in phagosomes or secondary lysosomes we conclude that movements of these organelles due to cytoplasmic motion caused relaxation. Magnetic particles might therefore serve as probes for cytoplasmic motility of Kupffer cells in situ.

Animals↗
PubMed1984

Respiratory tract structure and function.

The relationship between structure and function of the pulmonary gas-exchange apparatus and its comparative aspects is demonstrated in four sections: (1) the lung as gas exchanger, (2) the gas-exchange structures of the human lung, (3) comparative aspects of structure-function correlation, and (4) analysis of structure-function discordancy. Physical activity and body size are described to influence the structural dimensions of the pulmonary gas exchange apparatus in different ways. As far as the inhalation of toxic substances is concerned, different kinds of effects must therefore be taken into consideration, depending on an animal's size and metabolism; hence, experiments of comparative anatomy and physiology are desirable in order to find an appropriate animal model that permits extrapolation to humans.

Animals↗
PubMed1984

Airway macrophages. The importance of the fixation method.

Two methods of fixation, intravascular perfusion and intratracheal instillation, were compared with regard to the number, distribution, and appearance of airway and alveolar macrophages. With instillation of fixative, the number of airway macrophages present was reduced to only 32.6% of that seen after intravascular perfusion. Macrophages may have important physiologic and pathologic roles in the airways. The method of fixation is crucial for preservation of their numbers and location.

Animals↗
PubMed1984

Correlation between the behavior of magnetic iron oxide particles in the lungs of rabbits and phagocytosis.

Five New Zealand white male rabbits were exposed (30 min; 300 mg/m3) to a submicrometric magnetic iron oxide aerosol (gamma-Fe2O3) produced by burning iron pentacarbonyl in a reducing atmosphere. After aerosol inhalation, an external magnetic field was applied to the rabbits to magnetize and align the ferrimagnetic particles within their lungs. After removal of the external field, a remanent magnetic field was detectable at the body surface. Using a flux-gate magnetometer probe in an enclosure shielded against external magnetic noise, the peak remanent field after magnetization was measured periodically during the next 6 weeks. After each magnetization, the strength of the remanent field decayed rapidly with time (relaxation). The mechanism responsible is particle rotation caused by tissue, cell, organelle, or Brownian movement. The rate of relaxation changed with time after particle inhalation, especially during the first day; changes in the relaxation rate correlated with an estimate of in situ particle phagocytosis during that time. Analysis of pulmonary lavage fluid from 15 rabbits into which radioactive gold-198 had been intratracheally instilled showed that, at 1 hr after instillation, 27% of the gold had been phagocytized, whereas at 16 hr 91% had been ingested. The strength of the magnetic field immediately after each magnetization (that is, before relaxation) was used to estimate the amount of iron oxide in the lungs. At 1 day after exposure, 96.8 +/- 8.8% (mean +/- standard error) of the initial dust was still present; at 10 days, 67.9 +/- 16.2%; and at 40 days, 16.0 +/- 4.6%. It is concluded that ferrimagnetic particles can serve as an easily measured, long-lasting marker that can be used for noninvasive studies of clearance and of particle phagocytosis and as a probe for intracellular processes such as organelle motion.

Aerosols↗
PubMed1983

Maximal oxygen consumption and pulmonary diffusing capacity: a direct comparison of physiologic and morphometric measurements in canids.

The purpose of this study was to check the validity of the morphometric model for estimating physiological conductances for gases, DL. We make a direct comparison between the lung's conductance for carbon monoxide, measured physiologically using the single breath method, DLCO (sb), and that measured morphometrically using the previously published model, DLCO(mm). We also make a direct comparison between the maximum rate of oxygen uptake by the lung during exercise, VO2max, and the lung's conductance for oxygen DLO2(mm). We made these measurements on four species of canids (foxes, coyotes, dogs and wolves). We find a direct proportionality between morphometric and physiologic DLCO measurements, the morphometric being consistently larger by a factor of two. We also find that both DLCO and DLO2 increase more steeply with body mass than VO2max, the difference between the allometric slopes being the same as we had found previously in a wide range of mammalian species ranging from 2 g to 700 kg, although the slopes themselves were different. We conclude that the discordant scaling of DLO2 and VO2max with respect to body mass is not an artifact of the model for calculating DLO2 from morphometric data.

Animals↗
PubMed1983

Trypanocidal action of neuroleptic phenothiazines in Trypanosoma brucei.

This paper reports the effects of a series of phenothiazine derivatives on trypanosomes in vitro. Our results demonstrate that trypanosomes are very sensitive to some of these compounds at micromolar concentrations. Electron microscopic analysis of drug-treated cells shows that the pellicular layer of microtubules is selectively disintegrated by phenothiazine treatment, while the flagellar axoneme is entirely resistant to the drug. These observations suggest that phenothiazines might constitute a promising candidate group for the development of new trypanocidal drugs. Furthermore, they indicate that the mechanism of drug action is mediated through a specific interaction of phenothiazines with the pellicular, but not with the flagellar, microtubules.

Animals↗
PubMed1983

Behavior of magnetic particles in hamster lungs: estimates of clearance and cytoplasmic motility.

Ferrimagnetic particles suspended in saline were instilled intratracheally into the lungs of Syrian golden hamsters. The particles were magnetized and aligned by applying an external magnetic field. Upon removal of the external field, the particles produced a remanent magnetic field from the lungs which decayed due to random misalignment of the particles (relaxation). Magnetization and relaxation measurements were performed immediately after instillation, then repeatedly during the first 24 h, and finally at intervals of several days up to 30 days after the instillation. The size of the initial remanent magnetic field immediately following each external magnetization is a measure of the amount of iron oxide in the lungs. It decreased with time, reflecting particle clearance. The rate of relaxation increased steeply during the first 12 h after the instillation and decreased slowly between the 5th and 30th day. Changes in the location of particles from extracellular to intracellular sites and movements from ectoplasmic to endoplasmic sites within cells may be responsible for the observed changes in relaxation rates with time.

Animals↗
PubMed1982

Effect of cold environment on skeletal muscle mitochondria in growing rats.

Growing rats(4 weeks old) were kept for 3 weeks at 11 degrees C and 24 degrees C respectively. The cold-adapted animals showed a significantly higher oxygen consumption (64%). Volume density of subsarcolemmal and interfibrillar mitochondria as well as volume density of fat droplets were estimated in M. soleus and the diaphragm of both groups. In cold-adapted animals, the total volume of mitochondria was significantly increased by 24% in diaphragm and 37% in M. soleus. The volume of subsarcolemmal mitochondria was almost doubled in each muscle, but the volume of interfibrillar mitochondria did not change significantly. The surface of the inner mitochondrial membranes per unit volume of mitochondrion in M. soleus was significantly increased both in interfibrillar and subsarcolemmal mitochondria, whereas the surface of the outer mitochondrial membranes per unit volume of mitochondrion was increased only in the subsarcolemmal mitochondria. The volume of fat droplets in the diaphragm and M. soleus of cold adapted animals increased significantly by 62% and 150% respectively.

Adaptation, Physiological↗
PubMed1982

Cell number and cell characteristics of the normal human lung.

Eight normal human lungs obtained from patients dying from causes not related to the lung were subjected to morphometric analysis to determine the number of cells in the alveolar region and their mean volume and surface characteristics. The age range was 19 to 40 yr, average body weight was 74 kg, and the average fixed lung volume was 4,300 ml. The overall mean nuclear diameters of the nuclei of 5 major cell types in the lung parenchyma were found to have little variation, with means ranging from 7.54 to 8.77 micrometers. Alveolar type I epithelial cells were found to comprise 8% of the cells and to be one of the largest cells, having a mean volume of 1,764 micrometers 3 and covering an average of 5,098 micrometers 2 of alveolar surface. Seven percent of the alveolar surface was covered by alveolar type II cells, which make up 16% of the total alveolar cells and have a mean volume that is half that of the type I pneumocyte. Capillary endothelial cells make up 30% of the lung cells and were significantly smaller in both size and average surface area than the alveolar type I cells. Cells in the interstitial space comprised 37% of the total cells. The number of alveolar macrophages showed great variability, ranging from 19% of alveolar cells in 1 person to 3 to 5% in the nonsmoking females. The alveolar cell population characteristics found in resected lobes from 2 nonsmoking females were found to be similar to 2 nonsmoking females studied after autopsy. An interspecies comparison of characteristics of cells from the alveolar regions of normal lungs from humans, baboons, and rats showed that proportions of cells in the alveolar region and their average thickness, size, and surface areas were relatively constant.

Adult↗
PubMed1981

Allometric analysis of the morphometric pulmonary diffusing capacity in dogs.

The lung volume, the morphometrically determined alveolar and capillary surface area, and the capillary volume of 27 dogs (weight 2.65-57 kg) all were linearly correlated with body weight. The thickness of the air-blood barrier increased only slightly with increasing body size. The structural diffusing capacity, containing these parameters, was used to estimate the gas exchange capabilities of the lung and was also found to scale in direct proportion to body size. This coincides with reports on physiologically estimated diffusing capacity but is obviously different from the interspecies slope for metabolism which scales to the 3/4 power of body weight.

Animals↗
PubMed1981

Design of the mammalian respiratory system. IV Morphometric estimation of pulmonary diffusing capacity; critical evaluation of new sampling method.

The quality of morphometric data obtained by stereological methods depends on the sampling scheme adopted. In the light of recent advances in sampling theory for stereology a sampling strategy has been developed which differs significantly from that used in previous studies. It operates with a cascade of four sampling levels and adopts the principle of A-weighted sampling, a method that should eliminate bias and possibly yield smaller variances. This method is described and discussed in detail. When compared with the old simpler sampling approach it is found that the new method (1) is at least as efficient and (2) that the estimates of morphometric parameters obtained by this method are similar to the data generated by the old method.

Animals↗