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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 289 records · Page 16Linked to original sources

Automated image analysis of alveolar expansion patterns in immature newborn rabbits treated with natural or artificial surfactant.

Automated image analysis of histological lung sections was used to compare the efficacy of an artificial surfactant (dipalmitoylphosphatidylcholine + high-density lipoprotein, 10:1) and a natural surfactant (the phospholipid fraction of porcine surfactant, isolated by liquid-gel chromatography in ventilated immature newborn rabbits delivered after 27 days' gestation. Tidal volumes were significantly improved in each group treated with surfactant when compared with controls, but natural surfactant-treated rabbits had significantly higher tidal volumes than those receiving artificial surfactant. There were no statistically significant differences in alveolar expansion between the artificial surfactant group and the controls, but alveolar volume density and a shape factor (assessing the 'circularity' of terminal airspaces) were significantly higher in animals receiving natural surfactant. These animals also had a lower coefficient of variation of alveolar volume density and a lower alveolar average integral mean surface curvature, indicating a uniform pattern of alveoli with a smooth profile. We conclude that automated image analysis is useful for the quantitation of alveolar expansion patterns in immature neonatal lungs and that natural surfactant is superior to the artificial surfactant tested in the present study.

Animals↗

Involvement of prostaglandins in the immune alterations caused by the exposure of mice to ultraviolet radiation.

Our study was designed to analyze the possible involvement of prostaglandins in the mechanisms responsible for the depressions in contact hypersensitivity (CH) responsiveness observed in UVR-exposed animals. Low-dose UVR-exposed animals were found to exhibit a depressed capacity to elicit CH responses after hapten application to irradiated (devoid of Langerhans cells) or UVR-protected (normal Langerhans cells) dorsal skin surfaces. Normal responsiveness was observed in low-dose UVR-exposed animals sensitized through unirradiated ventral skin surfaces. Indomethacin treatment of low-dose UVR-exposed animals (to inhibit prostaglandin synthesis in vivo) caused a retention in the capacity to respond normally to CH induction to haptens applied to the nonirradiated, but not to irradiated, dorsal skin surfaces. High-dose UVR-exposed animals, which normally exhibit a depression in responsiveness to hapten sensitization, retained a normal capacity to elicit CH responses if treated with the drug indomethacin. These findings implicate prostaglandins in the pathogenesis of the immunologic hyporesponsiveness, observed in low- and high-dose UVR-exposed animals. Our studies also determined that under all experimental conditions where animals were contact sensitized through nonirradiated skin sites, CH-effector cells could be found in the draining lymph nodes. No CH-effector cells were observed in the lymph nodes of mice that were contact sensitized directly through irradiated skin sites. It was also found that the spleens of both UVR-exposed and normal animals contained adoptively transferrable suppressor cells subsequent to hapten application. This demonstration of CH-effector and CH-suppressor cells in both normal and UVR-exposed animals did not directly relate to the potential of the donor animals to elicit a CH response.

Animals↗

Scanning electron microscopy of epithelial lesions induced by artificial ventilation of the immature neonatal lung; the prophylactic effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation were ventilated artificially for 5-10 min with a peak insufflation pressure of about 35 cm H2O, with or without previous treatment with natural surfactant via the airways. The alveolar expansion pattern and the surface structure of the airways were then examined by scanning and transmission electron microscopy. Animals not receiving surfactant had very irregular alveolar expansion and showed prominent desquamation of the bronchiolar epithelium with a strikingly ragged appearance of the mucosa in the scanning electron microscopic images. Litter mates treated with surfactant had improved alveolar expansion and a flattened but otherwise nearly intact bronchiolar epithelium. The findings confirm the beneficial effect of surfactant replacement on the immature neonatal lung.

Animals↗

Effect of aminophylline on lung maturation in preterm rabbit fetuses.

Pregnant rabbit does were treated intravenously with aminophylline (6 mg/kg/day) from the twenty-fifth day after the day of mating, and the fetuses were delivered by hysterotomy on the twenty-eighth day. One group of neonates was breathing air, and another group 100% oxygen. Lung mechanics were evaluated in the newborn animals during spontaneous or artificial ventilation, and the lungs were studied histologically with particular reference to the alveolar volume density. In one series of experiments, the lungs were washed and the lavage fluid was analyzed for phosphatidylcholine and phosphatidylglycerol. Aminophylline-treated litters had greater body weights, an improved survival rate, and an increased amount of phosphatidylglycerol in lung lavage fluid. Respiratory frequency was increased in aminophylline-treated animals breathing air, but data on lung compliance showed no significant difference between treated and control animals. In the present model, the beneficial effect of aminophylline can be attributed largely to a combination of accelerated fetal growth and improved postnatal regulation of breathing and less to a specific influence on the biochemical and functional maturation of the lung.

Aminophylline↗

Nodular fasciitis: a case report.

A case of nodular fasciitis, an unusual, but certainly not rare, lesion is presented. The correct histologic diagnosis was made, and conservative surgical therapy was performed. Follow-up examination at 15 months revealed no residual or recurrent lesion.

Child↗

Rabbit lung after inhalation of hexa- and trivalent chromium.

Rabbits were exposed to aerosols of hexavalent (Na2CrO4) and trivalent chromium (Cr(NO3)3) at concentrations of 0.9 and 0.6 mg/m3 of chromium respectively for 4-6 weeks (5 days/week and 6 hr/day). Three of eight rabbits exposed to Cr(VI) and three of eight rabbits exposed to Cr(III) showed nodular accumulations of alveolar macrophages, similar to the lesions observed in previous experiments after exposure to Ni2+, Cd2+, or metallic nickel. Macrophages from rabbits exposed to Cr(III) usually contained round dark inclusions, large lysosomes, and laminated inclusions similar to the lamellar bodies in the type II cells, and most macrophages from rabbits exposed to Cr(VI) showed enlarged lysosomes. However, the total amount of phospholipids and the volume density of type II cells did not differ significantly between exposed rabbits and controls. Our findings indicate that the macrophages are directly affected by chromium. The accumulation of laminated structures in the alveolar macrophages after Cr(III) exposure might be due to an impaired catabolism of surfactant.

Administration, Inhalation↗

Experimental partial ureteric obstruction in newborn rats. VII. Are the long term effects on renal morphology avoided by release of the obstruction?

Partial obstruction of the left ureter was created in newborn rats. The obstruction was either permanent or was released after two or seven days. The effects were studied at the age of six weeks. The permanently obstructed kidneys characteristically exhibited considerable enlargement (X 18) of pelvic volume and prominent deformation of the papilla, frequently associated with moderate widening of collecting ducts and convoluted tubuli, and focal inflammatory and degenerative lesions. The weight difference between the hydronephrotic and the contralateral, intact kidney was significantly higher than in a sham operated group, although the combined kidney weight was unchanged, indicating a reduction on the obstructed side and a compensatory contralateral hypertrophy. In the group released after seven days, the pelvic volume had returned to normal; nevertheless the parenchymal weight pattern and the histological lesions were similar to those found in animals obstructed for six weeks. In the group released after two days, the pelvic volume had normalized, and the histological changes were less prominent than in animals obstructed for seven days or six weeks. Yet there was a significant difference in parenchymal weight between the hydronephrotic and the contralateral kidney, almost entirely caused by hypertrophy on the nonobstructed side. Thus, the ureteric obstruction must be released very early to avoid parenchymal weight reduction and curb the tissue lesions. On the other hand, the resulting parenchymal damage is moderate and does not seem to progress with time.

Animals↗

Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage.

Severe respiratory insufficiency was induced in adult guinea pigs by repeated lung lavage. The animals were then ventilated for 75 min with 100% O2, insufflation pressure 28/6-8 cmH2O (2.7/0.6-0.8 kPa), frequency 30/min, and 33% inspiration time. One group of animals (I) was treated with protein-depleted porcine surfactant, prepared by a combination of sucrose-gradient centrifugation, heating to 90 degrees C, and chloroform/methanol extraction. Another group (II) received the phospholipid fraction of porcine surfactant, isolated from minced lungs by chloroform/methanol extraction and liquid-gel chromatography. Surfactant was administered in two 1-ml doses (lipid concentration 90 mg/ml) instilled via the tracheal cannula about 15 and 45 min after the lavage procedure. Non-treated, lavaged animals served as controls. After 75 min of ventilation, control values for PaO2 and PaCO2 were 13.3 +/- 6.8 and 6.8 +/- 2.3 kPa (mean +/- s.d.), respectively. The corresponding values in Group I of surfactant-treated animals were 52.9 +/- 7.7 and 4.4 +/- 1.1 kPa, in Group II 53.5 +/- 7.3 and 4.8 +/- 1.3 kPa (P less than 0.02-0.002). The two groups of surfactant-treated animals also had significantly improved alveolar air expansion in histological sections, as reflected by increased alveolar volume density (0.67 +/- 0.05 and 0.62 +/- 0.11 vs 0.45 +/- 0.08 in controls; P less than 0.002). The benefits of surfactant replacement in this experimental model were thus similar to those previously observed in animal models of neonatal surfactant deficiency as well as in babies with respiratory distress syndrome (RDS). Our data suggest that surfactant replacement might have a therapeutic effect also in clinical adult RDS.

Animals↗

Effects of gamma-aminobutyric acid and (-)-baclofen on calcium and potassium currents in cat dorsal root ganglion neurones in vitro.

Calcium and potassium currents were examined in dialysed, isolated dorsal root ganglion neurones of the cat by use of a single electrode voltage clamp. Two calcium currents were identified, a low threshold inactivating (transient) current and a higher threshold slowly inactivating (sustained) current. Both currents were blocked by 1 mM cadmium and replacement of calcium with manganese, which revealed an underlying nonspecific outward current. The sustained current disappeared with internal dialysis over a period of 20 to 30 min. (-)-Baclofen (100 microM) and gamma-aminobutyric acid (GABA, 100 microM) were found to reduce the peak amplitude of the sustained calcium current, an effect which became more pronounced with increasing concentrations of external magnesium (1-5 mM). In 5 mM external magnesium, 100 microM baclofen reduced the calcium current by 28%. The voltage-activated delayed rectifier appeared to be the most prominent potassium current in these cells. We were unable to find any evidence for a significant contribution from calcium-activated potassium conductance or a transient potassium conductance under our recording conditions. Baclofen and GABA at 100 microM had no consistent effect on the voltage-activated potassium current. Baclofen did not change the resting potassium conductance.

Animals↗

Quantitative evaluation of neonatal lung expansion with automated image analysis.

Lung sections from artificially ventilated premature newborn rabbits, some treated with natural surfactant, were examined microscopically with an IBAS image analyzer connected to a television camera. The "stereological profile" of the alveoli was determined by automatical evaluation of the following parameters: volume density (VV), and its coefficient of variation (CV(VV), surface density (SV), average mean integral surface curvature (K), and a "shape factor" (SF) measuring the "circularity" of sectioned alveoli. Data from image analysis were closely correlated to those obtained with conventional morphometrical techniques (e.g., r = 0.92 for VV). Alveolar expansion was significantly improved after treatment with surfactant, especially in animals ventilated with prolonged inspiration phase. We suggest that image analysis is a useful method for evaluating alveolar expansion patterns in the neonatal lung.

Animals↗

Correlations between physical and physiological properties of various preparations of lung surfactant.

The physical and physiological properties of natural surfactant were investigated after the addition of various synthetic lipids. Three types of surfactant were studied: 1. Bovine surfactant with rapid spreading (1.6 s) and a relatively high minimal surface tension during surface compression (16 mN/m). 2. The same surfactant enriched with dipalmitoylphosphatidylcholine (DPPC), tripalmitin, and palmitic acid showing slow spreading (55 s) and low minimal surface tension (5 mN/m). 3. The same surfactant enriched with DPPC and dipalmitin, showing rapid spreading (1.8 s) and low minimal surface tension (6 mN/m). The physiological properties of these surfactants were evaluated in immature newborn rabbits. All three preparations effectively improved lung expansion and stability in pressure-volume recordings, increased tidal volumes during artificial ventilation, and enhanced alveolar volume density in histological sections. The magnitude of the therapeutic effects was similar for non-enriched and enriched materials. Thus, wide variations in in vitro surface properties do not seem to influence the in vivo activity of the surfactant preparations.

1,2-Dipalmitoylphosphatidylcholine↗

The role of the low-molecular weight (less than or equal to 15,000 daltons) apoproteins of pulmonary surfactant.

An artificial surfactant was prepared by combining synthetic dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol and the low-molecular weight (less than or equal to 15,000 daltons) surfactant apoproteins in the proportions 80:20:5. In the Wilhelmy balance, this surfactant formed a film with an equilibrium surface tension of 29 mN/m; surface tension was reduced to nearly zero during cyclic film compression, with effective respreadability during multiple compression-expansion cycles; similar surface properties were recorded with a pulsating bubble. When instilled into the airways of artificially ventilated immature newborn rabbits, the apoprotein-based artificial surfactant produced a five-fold increase in tidal volumes at insufflation pressure 25 cm H2O; this effect is similar to that obtained in previous experiments with natural surfactant phospholipids, administered in equal concentration (5 mg/ml). Higher concentration of the apoprotein-based surfactant could not be evaluated in vivo due to the high viscosity of the material. Systematic studies should be undertaken to find out whether an even more effective artificial surfactant could be prepared from the low-molecular weight apoproteins and other combinations of synthetic phospholipids.

1,2-Dipalmitoylphosphatidylcholine↗

Transganglionic transport of wheat germ agglutinin-HRP and choleragenoid-HRP in rat trigeminal primary sensory neurons.

Horseradish peroxidase conjugates of either the lectin wheat germ agglutinin (WGA-HRP) or choleragenoid (B-HRP) have been shown to be sensitive neuroanatomical tracers. In the present study a comparison was made between these two conjugates as transganglionic tracers in trigeminal primary sensory neurons following injection into the rat mystacial vibrissae skin. Differences between the two tracers were observed in the labeling of cell bodies in the trigeminal ganglion. Injection of WGA-HRP resulted in labeling of predominantly small cell bodies, whereas B-HRP gave rise to labeling of somewhat larger cell bodies. By increasing the concentration of the injected WGA-HRP solution the number of labeled cells increased substantially, while a corresponding increase in the concentration of B-HRP resulted in a relatively small increase in the number of labeled cells. WGA-HRP injection resulted in labeling of primary afferents mainly in the substantia gelatinosa of the trigeminal subnucleus caudalis. When the concentration of the injected WGA-HRP solution was increased, labeling was also observed in the marginal and magnocellular zones. Following B-HRP injection, labeling was only observed in the magnocellular zone and innermost part of the substantia gelatinosa. This general pattern of labeling was the same when the concentration of the B-HRP solution was increased.

Animals↗

Rabbit lung after inhalation of manganese chloride: a comparison with the effects of chlorides of nickel, cadmium, cobalt, and copper.

Rabbits were exposed to aerosols of MnCl2 (mass median aerodynamic diameter 1 micron) in metal concentrations of 1.1 and 3.9 mg/m3 for 4-6 weeks, 5 days/week, 6 h/day. The effects of alveolar type II cells, phospholipids, alveolar macrophages, and lung structure in general were compared with earlier reported effects of Ni2+, Cd2+, Cu2+, and Co2+. Except for a significant increase in the diameter of the alveolar macrophages after exposure to the higher Mn2+ concentration, no abnormalities were seen. The results of this and earlier studies indicate that these five metal ions have different, specific effects on the alveolar part of the lung.

Animals↗

Leakage of protein in the immature rabbit lung; effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.

Albumins↗