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Biomedical subjects

R Nilsson

Publications and source records attributed to R Nilsson.

At least 91 records · Page 5Linked to original sources

Microwave effects on the central nervous system--a study of radar mechanics.

Seventeen radar mechanics and engineers and 12 unexposed referents were examined, using extensive neurological, psychometric and neuropsychiatric techniques to determine whether there were any indications of central nervous system effects of microwave exposure. Pathological neurological findings were not more common in the exposed group than among the referents. In addition, the psychometric tests and the psychiatric rating scales did not reveal any statistically significant adverse effects of microwave exposure. The frequency of the occurrence of an increased protein band with an isoelectric point of 4.5 in the cerebrospinal fluid was higher among the men exposed to microwaves than among the referents. The nature and clinical significance of this or these proteins are still unclear. The time derivative of the magnetic flux density close to some of the transmitter units was surprisingly high (up to 350 T s-1).

Central Nervous System↗

Diagnosis of pulmonary embolism based upon alveolar dead space analysis.

Pulmonary embolism (PE) leads to an abnormal alveolar deadspace that is expired in synchrony with gas from normally perfused alveoli. This feature of PE separates it from pulmonary diseases affecting the airways, which are characterized by nonsynchronous emptying of compartments with an uneven ventilation/perfusion relationship. An analysis of the single breath test (SBT) for CO2, SBT-CO2, focusing on the late tidal expirate, was made in order to evaluate the feasibility to use the SBT-CO2 for the diagnosis of PE. The test was evaluated in 38 patients with suspected PE where pulmonary angiography showed that nine had PE and 29 did not. It was also tested in a reference population consisting of patients with normal lung function, obstructive lung disease and interstitial lung disease. Previously suggested gas exchange measurements for the diagnosis of PE, ie, the physiologic deadspace fraction, VDphys/VT, and the arterial-to-end-tidal CO2 gradient, P(a-E')CO2, were also evaluated in the groups. SBT-CO2 achieved a nearly complete separation between the patients with PE and those without. The other measurements, however, showed a substantial overlap between patients with PE and those with obstructive or interstitial lung disease. The SBT-CO2 is simple and potentially widely available and warrants further study as a routine technique for the diagnosis of PE.

Angiography↗

Non-palpable invasive breast carcinomas from the Stockholm screening project.

Sixty-six non-palpable, invasive mammary adenocarcinomas from the Stockholm mammography screening project were studied with respect to histopathology. In 53 of these tumors estrogen receptor (ER) content was estimated and in 30 of them also the DNA distribution pattern. The tumors were predominantly of low or intermediate histological malignancy grade and ER-rich, whereas the distribution of DNA ploidy equalled that found in a non-selected tumor material. Only 2 tumors recurred during follow-up (median 51 months), indicating that non-palpable breast carcinomas represent a prognostically favourable subset in spite of a relatively high proportion of aneuploid tumors.

Adenocarcinoma↗

Comparison of the mitogenic activities of streptococcal protein-G and staphylococcal protein-A on human mononuclear cells.

In the present work we report data from experiments comparing the proliferative stimuli demonstrated by Streptococcal Protein-G and Staphylococcal Protein A on human peripheral blood mononuclear cells. Protein-G and Protein-A are presented to the cells in solution as well as linked to plastic or Sepharose beads, or incorporated within the cell wall of whole bacteria. The cellular response is measured by incorporation of 3H-thymidine in 72 hr cultures. The soluble and the immobilized forms of Protein-A, but not those of Protein-G, displayed high mitogenicity. Possible explanations for the absence of Protein-G induced mitogenicity are discussed.

Bacterial Proteins↗

A novel approach to monoclonal antibody separation using high performance liquid affinity chromatography (HPLAC) with SelectiSpher-10 protein G.

Protein G, a bacterial cell wall protein extracted from strains of Streptococci, has been employed as a ligand in high performance liquid affinity chromatography (HPLAC) for separation of monoclonal antibodies. Examples are given of rapid high-resolution separations of rat and mouse monoclonal antibodies belonging to various subclasses. In comparison with protein A chromatography, we were able to show superior binding characteristics for SelectiSpher-10 protein G columns under conditions of 'low' ionic strength (about 0.1 M) and neutral pH (pH approximately 7). The monoclonal antibodies were isolated in high purity (greater than 90%) and with good recovery of specific activity (80-100%). We believe that the HPLAC technology based on SelectiSpher-10 protein G is of potential value in the analysis and purification of monoclonal antibodies from various species and subclasses.

Animals↗

Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.

Ten newborn infants (795-1680 g) with severe respiratory distress syndrome (RDS) were treated with the isolated phospholipid fraction of bovine or porcine surfactant, which was administered via the airways (dose 200 mg/kg), at a median age of 10.5 h. Before receiving surfactant, all the infants were on artificial ventilation (FiO2 0.6-1.0). Within 2 h after surfactant replacement, the arterial-to-alveolar PO2 ratio increased from 0.1 to 0.35. There was a concomitant improvement in lung aeration on the chest roentgenograms and a significant reduction in the right-to-left shunt. Four patients died of cerebral hemorrhage; two of them also had a patent ductus arteriosus. One surviving infant developed bronchopulmonary dysplasia, and another succumbed 8 months later to the sudden infant death syndrome. No antibodies against surfactant were detected in the sera of the survivors. Since our results show a significant improvement in lung function after replacement therapy, the efficacy of this new surfactant preparation should be further tested in randomized clinical trials.

Chromatography, Gel↗

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↗

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↗

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↗

Bronchiolar epithelial lesions in spontaneously breathing premature newborn rabbits.

Premature rabbit neonates were stimulated to breathe for time periods varying between 5 and 150 min. The distribution of bronchiolar epithelial lesions was determined morphometrically. Animals breathing for 5-10 min had no lesions. Focal necrosis and desquamation of bronchiolar epithelium were found in 36 of 46 animals breathing for 15-150 min. These lesions were similar to those previously observed in premature rabbit neonates after a few minutes of artificial ventilation.

Animals↗

Surfactant treatment and ventilation by high frequency oscillation in premature newborn rabbits: effect on survival, lung aeration, and bronchiolar epithelial lesions.

Premature rabbit neonates delivered at gestational age 27 days were ventilated by high frequency oscillation for 60 min with 100% O2, using a frequency of 7-8 Hz, 50% inspiration time and mean airway pressures of 6-8 cm H2O. Twenty-five animals received bovine surfactant (2 ml/kg body weight; phospholipid concentration 85-100 mg/ml) in the tracheal cannula before onset of ventilation, and 22 littermates served as controls. In the surfactant-treated group, average tidal volume was about 10 times larger than in controls, yet only 15% of the estimated dead space. Judged from ECG recordings, the treated animals also had a much higher survival rate: 96 versus 5% (p less than 0.001). Morphometrically, mean alveolar volume density was increased in the surfactant-treated animals in comparison with controls: 0.65 +/- 0.08 versus 0.37 +/- 0.08 (means +/- SD; p less than 0.005). Bronchiolar epithelial lesions were found in all control animals and were severe in almost all cases. In the surfactant-treated group, epithelial lesions were absent in 12, mild in 11, and fairly prominent in two animals. We conclude that after treatment with surfactant, the premature newborn rabbit can be ventilated adequately with high frequency oscillation at comparatively low mean airway pressures and that surfactant replacement effectively reduces the development of epithelial lesions in conducting airways during high frequency oscillation.

Animals↗

Physiological activity of pulmonary surfactant with low protein content: effect of enrichment with synthetic phospholipids.

A natural surfactant with low protein content (1%) was prepared by a sequence of cold centrifugation, heating to 90 degrees C, sucrose-gradient centrifugation, and extraction with chloroform:methanol. Some of the material was enriched with dipalmitoylphosphatidylcholine (DPPC) and unsaturated phosphatidylglycerol (PG) to relative concentrations of 56% and 10%, respectively. The in vitro physical properties of these preparations were evaluated with pulsating bubble and Wilhelmy balance and their in vivo activity with experiments on artificially ventilated premature newborn rabbits, delivered on day 27 of gestation. The animals were kept in body plethysmographs at 37 degrees C and ventilated artificially with a standardized sequence of insufflation pressures: 25, 20, and 15 cm H2O. The lungs were fixed by vascular perfusion and the alveolar expansion evaluated morphometrically in histologic sections. Enrichment of surfactant with DPPC and PG resulted in lower minimal surface tension during surface compression but did not further improve lung compliance or the alveolar expansion pattern. Treatment with nonenriched surfactant at a phospholipid concentration of 100 mg/ml (individual dose = 200 mg/kg) caused a markedly increased lung compliance at all insufflation pressure levels (p vs. controls less than .01). Our data indicate that pulmonary surfactant remains physiologically active after removal of most of its protein components and that enrichment with DPPC and PG reduces the in vitro minimal surface tension without adding to the in vivo efficacy.

Animals↗

Antigen-independent binding of rat immunoglobulins in a radioimmunoassay. Solutions to an unusual background problem.

A high non-specific binding of immunoglobulins to plastic surfaces was noted with a number of rat sera, when tested in an indirect 125I-labeled protein-A assay for detection of cell-surface-bound rat immunoglobulins of various classes and IgG subclasses. This type of non-specific binding was found with all types of Ig. The degree of binding varied with the type of test plate used and fluctuated with time among sera drawn sequentially from the same donors. Coating test wells with fetal calf serum supplemented with BSA, gelatin or fibrinogen did not eliminate the reactions. The immunoglobulins bind directly to the polystyrene, and not to antigens present in fetal calf serum or autoantigens in rat serum. Two different approaches were used to eliminate the nonspecific reaction. When living cells were used as target antigens, exclusively cell-bound radioactivity was eluted with the non-ionic detergent Nonidet P40, which solubilizes the cell membrane without breaking the protein-A/rabbit IgG, rabbit IgG/rat Ig, or rat Ig/plastic interactions. When rat serum antibodies are tested on target antigens adsorbed on non-tissue culture grade plates, non-specific binding may be avoided by including 0.05% Tween 20 in the incubation mixture.

Adenocarcinoma↗