Biomedical subjects

H Lum

Publications and source records attributed to H Lum.

45 records · Page 3Linked to original sources

PubMed1989

Calcium dependence of the thrombin-induced increase in endothelial albumin permeability.

We examined whether the increase in endothelial albumin permeability induced by alpha-thrombin is dependent on extracellular Ca2+ influx. Permeability of 125I-albumin across confluent monolayers of cultured bovine pulmonary artery endothelial cells was measured before and after the addition of 0.1 microM alpha-thrombin. In the presence of normal extracellular Ca2+ concentration ([Ca2+]o, 1000 microM), alpha-thrombin produced a 175 +/- 10% increase in 125I-albumin permeability. At lower [Ca2+]o (100, 10, 1, or less than 1 microM), alpha-thrombin caused a 140% increase in permeability (P less than 0.005). LaCl3 (1 mM), which competes for Ca2+ entry, blunted 38% of the increase in permeability. Preloading endothelial monolayers with quin2 to buffer cytosolic Ca2+ (Cai2+) produced a dose-dependent inhibition of the increase in 125I-albumin permeability. Preincubation with nifedipine or verapamil was ineffective in reducing the thrombin-induced permeability increase. A 60 mM K+ isosmotic solution did not alter base-line endothelial permeability. alpha-Thrombin increased [Ca2+]i in a dose-dependent manner and the 45Ca2+ influx rate. Extracellular medium containing 60 mM K+ did not increase 45Ca2+ influx, and nifedipine did not block the rise in 45Ca2+ influx caused by alpha-thrombin. Ca2+ flux into endothelial cells induced by alpha-thrombin does not occur through voltage-sensitive channels but may involve receptor-operated channels. In conclusion, the increase in endothelial albumin permeability caused by alpha-thrombin is dependent on Ca2+ influx and intracellular Ca2+ mobilization.

Animals↗

PubMed1989

Pulmonary edema after pulmonary artery occlusion and reperfusion.

We examined the basis of reperfusion-induced pulmonary edema produced by pulmonary artery occlusion and subsequent reperfusion. After a 24-h period of occlusion of a rabbit pulmonary artery followed by a 2-h period of reperfusion, the lungs were removed from the animal and perfused with a 0.5 g% Ringer's-albumin solution. An increase in lung weight was observed within 60 min compared with control lungs (i.e., lungs subjected to pulmonary arterial occlusion but not reperfusion) (p less than 0.05). Shorter periods of occlusion (6 or 12 h) did not result in edema, which suggests that a period of ischemia was required for the reperfusion-induced pulmonary edema. The extravascular lung water content also increased in the contralateral lung (i.e., the lung not subjected to pulmonary arterial occlusion and reperfusion). The capillary filtration coefficient increased in reperfused lungs compared with controls (p less than 0.05), indicating an increase in lung vascular permeability following reperfusion. Infusion of allopurinol (a xanthine oxidase inhibitor) and superoxide dismutase during the reperfusion period prevented the increases in lung weight and vascular permeability; infusion of catalase was ineffective. We conclude that pulmonary reperfusion following pulmonary artery occlusion increases pulmonary vascular permeability, which is mediated by the generation of oxidants.

Animals↗

PubMed1988

Selectivity of the endothelial monolayer: effects of increased permeability.

We investigated the mechanism of thrombin-induced increases in endothelial monolayer permeability by examining the effect of thrombin on the molecular sieving characteristics of the endothelial monolayer and comparing the responses of arterial- and venous-derived endothelial cell lines. Bovine pulmonary artery (BPA) and pulmonary vein (BPV) endothelial cells were similarly harvested and cultured. The endothelial cells were grown to confluence on gelatinized polycarbonate filters and the permeabilities to sucrose, albumin, and IgG were measured and corrected for effects of unstirred layers. The control permeabilities of BPA and BPV were similar with both monolayers, demonstrating selectivity to different sized tracer molecules. alpha-Thrombin (10(-6) M) increased the permeability of both BPA and BPV to albumin and sucrose. The permeability of BPA was increased to a greater extent than BPV, perhaps due to phenotypic differences. In both cell lines, the permeability increase was most pronounced for albumin, which by pore theory is best described by an increase in the radius of the small pore pathway for diffusion.

Animals↗

PubMed1987

A species comparison of alveolar size and surface forces.

The independent roles of alveolar size and surface tension in relation to lung stability were investigated in 11 different mammalian species whose body weight ranged from 0.03 to 50 kg. This range in species provided a wide variation in subgross anatomy as well as a fourfold range in alveolar diameter. Alveolar diameter was estimated from the mean linear intercept (Lm) of fixed lungs. Quasi-static pressure-volume curves were determined in excised lungs and the percent volume remaining on deflation from total lung capacity at 30 cmH2O to 10 cmH2O (%V10) provided an index of deflation stability related to functional surfactant. Surface tension of lung extract was measured in the Wilhelmy balance, and the minimum surface tension measured provided an index of surface tension lowering capacity of surfactant. Relationships of %V10 with alveolar diameter and surface tension with alveolar diameter were examined for correlations. Our results indicated that despite a range in Lm between 31 and 133 micron (mouse to pig), %V10 did not change in proportion with Lm across species. Similarly, minimum surface tension was about the same (6.1 to 8.8 dyn/cm) across a threefold difference in alveolar diameter. These results suggest that a stable alveolar configuration is maintained by both surface and tissue forces in a complex manner yet to be analyzed.

Animals↗

PubMed1985

Effects of 10% formalin fixation on fixed lung volume and lung tissue shrinkage. A comparison of eleven laboratory species.

This species comparative study examined tissue shrinkage from a known physiologic lung volume through to the processed histologic section. Eleven mammalian species with body weights that spanned 3 orders of magnitude were studied. Air pressure-volume curves were determined to obtain total lung capacity (TLC) at 30 cmH2O. The lungs were then fixed by airway filling at 25 cmH2O pressure, and a displacement fixed lung volume was determined. Linear dimensions were systematically measured on fixed tissue blocks, embedded tissue blocks, and stained sections. Results indicated that the ratio of fixed lung volume to TLC ranged between 0.6 and 2.0. The corresponding ratios for linear dimensions ranged between 0.8 and 1.3 for all species. Histologic processing caused further shrinkage; the ratios of linear dimensions measured after and to those measured before processing ranged between 0.6 and 0.7. Thus, the degree of fixed lung volume achieved relative to TLC varies considerably more among species than does the histologic shrinkage caused by processing. We conclude that measurement of these changes in lung dimensions caused by fixation and histologic processing in the different species is essential, particularly in quantitative interspecies physiologic studies.

Animals↗

PubMed1983

Morphometry of in situ and lavaged pulmonary alveolar macrophages from control and ozone-exposed rats.

Effects of ambient levels of ozone on cell size and compartments were determined morphometrically for both in situ and lavaged pulmonary alveolar macrophages from rats exposed to filtered air or to filtered air with 0.60 ppm ozone. The ozone exposure was 8 hr/day for 3 days. Significant exposure-related compartmental volume density changes of in situ centriacinar macrophages were: decreased endoplasm (p less than 0.01); increased lysosome-like structures (p less than 0.01); decreased primary lysosomes (p less than 0.01); increased small and large secondary lysosomes (p less than 0.001); and decreased phagosomes/autophagosomes (p less than 0.05). In lavaged macrophages, the only significant exposure-related change was an increase in the density of large secondary lysosomes (p less than 0.01). Mean profile areas of in situ centriacinar macrophages from control and exposed rats were 86.94 micrometers2 and 112.04 micrometers2, respectively. The average mean cell volume V and mean caliper diameter D of macrophages lavaged from control rats were 1128.45 micrometers3 and 12.92 micrometers, respectively, whereas those from exposed rats were 1583.08 micrometers3 and 14.46 micrometers, respectively. Exposure-related increases in cell size were seen in both in situ and lavaged macrophages, but more significant differences in cell compartments were seen in the in situ centriacinar macrophages. Morphometry of pulmonary alveolar macrophages after ambient levels of ozone indicated increased uptake, storage, or both rather than cell damage. Comparison of in situ centriacinar and lavaged macrophages from both control and exposed rats revealed significant differences in their volume fractions of nucleus, cytoplasm, ectoplasm, mitochondria, lysosome-like structures, lipid droplets, vacuoles, and phagosome/autophagosomes. These differences between centriacinar and lavaged macrophages indicate different cell populations are sampled by these two methods.

Animals↗

PubMed1978

A comparative study of cell renewal after exposure to ozone or oxygen. Response of terminal bronchiolar epithelium in the rat.

Cell renewal patterns of the terminal bronchiolar epithelium of rats were examined during 7-day exposures to either 0.8 ppm of ozone or 80 per cent O2. Terminal bronchiolar epithelial cells were classified and counted in ciliated, nonciliated secretory (Clara), and nonciliated, nonsecretory categories. Thymidine labeled with hydrogen-3 was used in conjunction with light microscopic autoradiography to obtain labeling indices in exposed rats at 6, 24, 72, and 168 hours compared to control rats at 6 and 168 hours. Results indicated that both ozone and O2 initiated a proliferative response of terminal bronchiolar epithelium, but that the response to O2 insult was delayed in onset and of lesser magnitude. Most importantly, the differential cell counts revealed that nonciliated secretory cells were the primary proliferating cell type at all periods after oxidant insult. This proliferative response continued with persistence of the insult through 168 hours. Shifts in proportions of cell types and labeling indices during exposure supported the view that nonciliated secretory cells are the reparative bronchiolar cells and that new ciliated cells are mainly derived from them.

Animals↗

PubMed1978

Morphometric and morphologic evaluation of pulmonary lesions in beagle dogs chronically exposed to high ambient levels of air pollutants.

Beagle dogs (104) comprising one control and seven treatment groups were exposed 16 hours daily for 68 months to filtered air, raw or photochemically reacted auto exhaust, oxides of sulfur or nitrogen, or their combinations. After a further 32 to 36 months in clean air, morphologic examination of lungs by light microscopy, scanning electron microscopy, and transmission electron microscopy revealed two important exposure-related lesions. They were enlargement of air spaces in proximal acinar regions, with and without increases in the number and size of interalveolar pores, and hyperplasia of nonciliated bronchiolar cells. Proximal enlargment of air spaces was most severe, both subjectively and morphometrically, in those dogs exposed to oxides of nitrogen, oxides of sulfur, or oxides of sulfur with photochemically reacted auto exhause. In contrast, hyperplasia of nonciliated bronchiolar cells was most severe in dogs exposed to raw auto exhaust alone or with oxides of sulfur. The air space enlargement and hyperplasia of bronchiolar epithelium correlated with functional impairment reported as occurring in these dogs. Foci of ciliary loss with and without squamous metaplasia were occasionally observed in trachea and bronchi. The observations indicate that enlargement of proximal acinar air spaces with some loss of interalveolar septa can develop in the absence of alveolar fenestrations. The persistnt nature of bronchiolar cell proliferations in such circumstances was also demonstrated. Two major toxicologic implications are (1) the production of permanent lung damage by much lower concentrations of pollutants than previously reported and (2) the apparent lack of additive or synergistic effects between oxidant gases and sulfur oxides.

Air Pollutants↗

PubMedDate not supplied

Culture and characterization of pulmonary microvascular endothelial cells.

Surface proteins were compared in endothelial cells (EC) obtained from bovine peripheral lung, pulmonary artery and vein, and dorsal aorta using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Galactose-containing glycoproteins [molecular weight (M(r)) 160-220 and 40 kDa] binding to the Ricinus communis agglutinin (RCA) and peanut agglutinin (PNA) were selectively observed on pulmonary microvessel EC as compared to EC from pulmonary artery, pulmonary vein, and dorsal aorta. The unique RCA- and PNA-binding profiles of EC from the pulmonary artery and microvessels may be important in characterizing EC from different sites in the pulmonary circulation. The pulmonary microvessel EC monolayer was also 15-fold more restrictive to transendothelial flux of [14C]sucrose (M(r) = 342 Da) than the pulmonary artery EC monolayer. In contrast, the microvessel EC were only six- and twofold more restrictive to the flux of larger tracer molecules, ovalbumin (M(r) 43 kDa) and albumin (M(r) = 69 kDa) than pulmonary artery EC. The greater restrictiveness of pulmonary microvessel EC monolayer indicates a major phenotypic difference in the cultured pulmonary microvessel EC barrier function.

Animals↗