Biomedical subjects

P Camner

Publications and source records attributed to P Camner.

At least 55 records · Page 3Linked to original sources

PubMed1993

Bronchial reactivity, lung function, and serum immunoglobulin E in smoking-discordant monozygotic twins.

Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2-delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers.

Adult↗

PubMed1993

Deposition in asthmatics of particles inhaled in air or in helium-oxygen.

Ten subjects with asthma inhaled 3.6 micron particles labeled with 111In in air and in a helium-oxygen mixture (He-O2) at 0.5 and at 1.2 L/s. Lung retention was measured after zero and after 24 h, and the percentage 24-h retention (Ret24) was taken to represent the fraction deposited in the alveolar part of the lung. For both inhalation rates, Ret24 was significantly higher when particles were inhaled with He-O2 than with air. The increase in Ret24 seemed to be larger in subjects with asthma than in healthy persons earlier studied. Ret24 was correlated with changes in both large and small airways, especially when the particles were inhaled with He-O2. Our data suggest that inhalation of drugs in He-O2 might be of therapeutic value when treating patients with severely obstructed airways.

Administration, Inhalation↗

PubMed1992

Macrophage reaction in rabbit lung following inhalation of iron chloride.

Groups of eight rabbits were inhalation-exposed to iron, 1.4 +/- 0.7 mg/m3 (low Fe), or 3.1 +/- 1.8 mg/m3 (high Fe) as FeCl3 or to filtered air (controls) for 2 months, 5 days/week and 6 hours/day. The alveolar macrophages were increased in number in both exposed groups. Noduli of granular macrophages were found in lungs of all the rabbits in the high-Fe group, in one from the low-Fe group, and in one control rabbit. Especially in the high-Fe group there were prominent changes in the macrophages such as enlarged lysosomes containing fibrous-looking structures, iron-rich inclusions, and densely packed, 5-nm electron-dense granules. The number of cells filled with surfactant-like inclusions as well as a smooth surface was increased in the high-Fe group and the macrophages had enhanced phagocytic capacity. There was an increase in the phospholipid concentration and in the volume density of type II cells in the high-Fe group but the level of phosphatidylcholines was not significantly changed. The fact that Fe3+ affected mainly the alveolar macrophages might be due to the relatively high concentration of iron in these cells caused by the precipitation of iron in their lysosomes.

Administration, Inhalation↗

PubMed1992

Rabbit lung after combined exposure to soluble cobalt and trivalent chromium.

Eight rabbits were exposed to 0.7 +/- 0.4 mg/m3 Co2+ as CoCl2 and 1.2 +/- 0.7 mg/m3 Cr3+ as Cr(NO3)3 (group Co + Cr), eight to 0.6 +/- 0.5 mg/m3 Co2+ (group Co), and eight to filtered air (control group), for 4 months, 5 days/week, and 6 hr/day. All rabbits in group Co + Cr and group Co showed nodular aggregation of alveolar epithelial type II cells. Volume density of the type II cells was significantly higher in group Co + Cr than in group Co and the control group. There was intraalveolar macrophage accumulation in seven rabbits in group Co + Cr, one in group Co, and one in the control group. In lavage fluid the numbers of macrophages and the percentage of these cells with smooth surface and intracellular surfactant-like inclusions were more increased in group Co + Cr than in group Co as were oxidative metabolic and phagocytic activities of the macrophages. Total phospholipids, phosphatidylcholines, and especially 1,2-dipalmitoylphosphatidylcholine was markedly increased in group Co + Cr whereas only 1,2-dipalmitoylphosphatidylcholine was slightly increased in group Co. One mechanism behind the high amount of surfactant phospholipids in group Co + Cr seems to be an enhanced production of surfactant by the type II cells. Another mechanism is probably that Cr3+ reduces the capacity of alveolar macrophages to catabolize surfactant. The results imply that it is important to investigate effects of combinations of cobalt and chromium in the occupational environment.

Animals↗

PubMed1992

Intraphagolysosomal pH in canine and rat alveolar macrophages: flow cytometric measurements.

Intracellular dissolution of inhaled inorganic particles is an important clearance mechanism of the lung and occurs in phagolysosomal vacuoles of phagocytes. Flow cytometric measurements of intraphagolysosomal pH in alveolar macrophages (AM) obtained from beagle dogs, Wistar rats, and from a baboon were made using fluorescein isothiocyanate-labeled amorphous silica particles (FSP). AM were obtained by bronchoalveolar lavage. FSP were phagocytized by AM in cell suspensions incubated in full media for 24 hr up to 6 days. Dual laser flow cytometry was performed and six-parameter list mode data were recorded from forward scatter, side scatter, and fluorescence intensities at 530 nm excited at 457 nm and 488 nm as well as logarithmic fluorescence intensity at wavelengths 630 nm excited at 488 nm. In this way it was possible to discriminate viable AM with phagocytized FSP from lysing AM with phagocytized FSP and from cells without FSP and from free FSP. Viable cells were distinguished from lysing cells by staining with propidium iodide immediately before the flow cytometric measurement. A calibration curve for the pH value was determined from FSP suspended in buffered media at pH values ranging from 3.5 to 7.5. First flow cytometrical results indicated that after an incubation time of 24 hr, the mean intraphagolysosomal pH of viable AM was 4.7 +/- 0.3 for dogs and 5.1 +/- 0.5 for rats. The intraphagolysosomal pH of the baboon AM was 4.5.

Animals↗

PubMed1992

Phagolysosomal pH in alveolar macrophages.

We studied phagolysosomal pH in alveolar macrophages (AM) using fluorescein-labeled yeast (FYP) and silica particles (FSP) as probes. Fluorescence intensities from the ingested test particles were measured on populations of AM using fluorescence spectrometry and on individual phagolysosomes using fluorescence microscopy. Measurements were performed on rabbit AM, which had been incubated with FYP or FSP (in vitro procedure). We also instilled FYP or FSP via the trachea into rabbit lungs and after 1 day, 1 week, 1 month, and 3 months lavaged the lungs and measured the pH in AM (in vivo procedure). Phagolysosomal pH was independent of the number and size of the fluorescent particles. Measurements of populations of AM with fluorescence spectrometry and of individual phagolysosomes with fluorescence microscopy gave similar average pH. For the FYP, pH decreased during the first day after lavage both in the in vitro and the in vivo procedures. For the FSP, pH was unchanged during the same period. After 1 day pH was similar for both particles. Electron microscopy showed a larger number of lysosomes in contact with phagosomes and a higher percentage of vacuolated phagosomes for FYP than for FSP. In the in vivo procedure, pH was unchanged at least up to 1 month, and this pH was lower than that in the in vitro procedure. The difference was probably due to conditions at the time of phagocytosis. Particles retained in the lung parenchyma were within AM, and their location within the AM appeared unchanged from 1 week up to 3 months.

Animals↗

PubMed1992

Phagolysosomal pH and dissolution of cobalt oxide particles by alveolar macrophages.

We studied phagolysosomal pH in rabbit alveolar macrophages (AM) incubated with 0-15 microM chloroquine. There was a dose-related increase in pH with chloroquine concentration. Electron microscopy showed that chloroquine increased lysosomal size. In a second experiment we studied dissolution of radiolabeled cobalt oxide particles by rabbit AM, phagolysosomal pH, and lysosomal size. The cells were incubated for 2 days with 0, 2.5, and 10 microM chloroquine. Size and pH increased with chloroquine concentration. Dissolution of cobalt particles by the AM did not clearly change with pH. In a third experiment, dissolution of cobalt oxide particles in 0.1 M acetate buffer in saline with pH 4.0, 5.0, and 6.0 was studied. At the same pH, dissolution in acetate buffer was faster than in the AM, and the dissolution appeared to decrease faster with increasing pH than in the AM. A simple model for dissolution of a particle in a phagolysosome was proposed. This model predicts the types of differences in dissolution between AM and buffered saline.

Animals↗

PubMed1992

Reaction of alveolar macrophages to inhaled metal aerosols.

For more than a decade we have exposed rabbits to different metals, usually in soluble form, and investigated the effects on the lungs. The metal concentrations have been around 1 mg/m3,i.e., not more than a factor of 10 above occupational threshold limit values. The exposure periods have been 1-8 months (6 hr/day, 5 days/week). We have studied especially the morphology and function of alveolar macrophages (AM), the morphology of alveolar type I and type II epithelial cells, and analyzed lung phospholipids. Several metals produce specific, complex effects. For example, metallic and soluble nickel (NiCl2) increase both number and size of the type II cells, increase the production of surfactant, and affect morphology and function of AM. Cobalt (CoCl2) induces a different effect on type II cells from nickel, causing the formation of nodules in these cells. Trivalent chromium [Cr(NO3)3] does not affect either type II cells or the amount of surfactant significantly, but markedly affects AM. The administered metals affect AM both directly and indirectly. For example, nickel induces an increased production of surfactant, resulting in overfed AM with an increased metabolic activity. However, nickel also induces a direct decrease in the release of lysozyme activity by AM. Our results emphasize the complexity of the effects on the lungs of inhaled agents, which can act both directly and indirectly on AM.

Administration, Inhalation↗

PubMed1992

Alveolar macrophages and lung lesions after combined exposure to nickel, cobalt, and trivalent chromium.

In earlier inhalation exposures of rabbits, nickel increased the production of surfactant by type II cells, with secondary effects on morphology and function of alveolar macrophages. Cobalt induced mainly a nodular growth pattern of the type II cells. Trivalent chromium seemed to impair the capacity of macrophages to catabolize surfactant but did not affect the type II cells. We exposed rabbits by inhalation to combinations of nickel (0.6 mg/m3 as NiCl2) and trivalent chromium [1.2 mg/m3 as Cr(NO3)3] (Ni-Cr), cobalt (0.5 mg/m3 as CoCl2) and nickel (0.5 mg/m3) (Co-Ni), or cobalt (0.5 mg/m3) and chromium (1.2 mg/m3) (Co-Cr) for 4 months, 5 days/week, 6 hr/day. Alveolar macrophages, alveolar type II cells, and lung content of phospholipids were determined. All combined exposures induced more pronounced lung lesions than exposures for each of the metals. Phospholipid concentrations were significantly higher. There were significantly higher percentages of macrophages filled with surfactant-like inclusions and a smooth surface. Accumulations of macrophages in alveoli were more widespread. Chromium potentiated the effects of nickel and cobalt on the type II cells, which led to secondary effects on the macrophages. Nickel potentiated the specific effects of cobalt, i.e., type II cell nodule formation. The result indicates that noxious effects could also be induced in man by combined exposure to nickel, cobalt, and trivalent chromium in concentrations similar to those occurring in some occupational settings.

Animals↗

PubMed1991

[Lysozyme--an enzyme of both historical and current interest as a therapeutical agent].

Lysozyme, a bacteriolytic protein discovered by Fleming in 1922 and found to be phylogenetically ancient and almost ubiquitous among living organisms, is probably the most studied enzyme in biology and medicine. Evidence of its involvement in resistance to bacterial infection is compelling but remains indirect. Muramyl peptides (fragments of bacterial cell wall peptidoglycan) exert many effects on the immune system and the CNS, and appear to contribute to non-specific resistance to infection, fever, fatigue, and the pathogenesis of bacterial infection. Synthetic muramyl peptide analogues are currently used as adjuvants in vaccine trials in humans. Several pathological conditions are associated with changes in lysozyme concentrations, and egg-white lysozyme treatment has been tried on a small scale. With the cloning of the human lysozyme gene in yeast cells the enzyme can now be produced on a large scale, which will enable its therapeutic applications to be evaluated.

Bacterial Infections↗

PubMed1991

Phagolysosomal pH and location of particles in alveolar macrophages.

Fluorescein-labeled silica particles (FSP) were instilled into the tracheae of rabbits. Groups of four rabbits were killed after 24 hr, 1 week, 1 month, or 3 months and their lungs were lavaged. Phagolysosomal pH in the alveolar macrophages (AM) was measured using microscope fluorometry with FSP as a probe. Due to the marked decline of the fluorescence intensities from the FSP between 1 and 3 months after instillation, it was not possible to measure pH at 3 months, but the values from 24 hr, 1 week, and 1 month were quite similar, with group means of 4.8 and 4.9, respectively. Phagolysosomal pH in AM which phagocytized the FSP in vitro showed values about half a pH unit higher. AM from rabbits lavaged at 1 week had more lysosomes in contact with the FSP-containing phagolysosomes and a higher degree of vacuolization between the FSP and the phagolysosomal membrane than AM lavaged at 1 day. The location of the FSP in the AM appeared to be similar in rabbits lavaged after 1 week and 3 months. In histologic sections from the lungs the large majority of the FSP were within cells at all time points.

Animals↗

PubMed1991

Lung lesions after combined inhalation of cobalt and nickel.

Rabbits inhaled 0.5 mg/m3 Co2+ as CoCl2, a combination of 0.5 mg/m3 Co2+ as CoCl2 and 0.5 mg/m3 of Ni2+ as NiCl2, or filtered air (controls) for 4 months, 5 days/week, 6 hr/day. The pattern of morphological effects on lung tissue and alveolar macrophages after the simultaneous exposure to Co2+ and Ni2+ was a combination of the patterns seen after exposure to Co2+ and Ni2+ alone. However, nickel seemed to potentiate the specific effect of cobalt, i.e., the formation of noduli of type II cells. Further, the increase in phospholipids, especially in 1,2-dipalmitoylphosphatidylcholine, appeared more pronounced after the combined exposure than after the additive combination.

Administration, Inhalation↗

PubMed1991

Regional deposition of 3.6-micron particles and lung function in asthmatic subjects.

In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.

Administration, Inhalation↗

PubMed1991

Bronchial reactivity and allergy-promoting factors in monozygotic twins discordant for allergic rhinitis.

Bronchial reactivity was studied twice in eight monozygotic twin pairs discordant for allergic rhinitis with pollen hypersensitivity, during the winter season (all eight pairs) and during the pollen season (seven pairs). On both occasions, the allergic twins showed significantly higher reactivity than their nonallergic siblings. The results indicate that moderate allergic rhinitis is associated with increased bronchial reactivity. This increased reactivity is an acquired trait; however, bronchial reactivity is not constantly increased in pollen rhinitis and may be normal even during the pollen season. The symptoms of allergic rhinitis usually started in childhood before the separation of the siblings. We could not demonstrate any major differences in exposure to allergens or airway irritants between the siblings. The allergic twins tended to have lower birth weight and insufficient weight increase just after birth.

Adult↗

PubMed1990

Bronchial reactivity and atopy in asthma discordant monozygotic twins.

Bronchial reactivity was studied in six asthma-discordant monozygotic twin pairs. In four pairs, atopy was confirmed in the asthmatic twin. It was not confirmed in any of the nonasthmatics. In five pairs, the asthmatic twin was markedly more reactive than the nonasthmatic partner. Bronchial reactivity correlated significantly with total IgE. The results indicate that hyperreactivity and atopy were acquired.

Adult↗

PubMed1989

Lung lesions after experimental combined exposure to nickel and trivalent chromium.

Rabbits were exposed to a combination of 0.7 mg/m3 of Ni2+ as NiCl2 and 1.2 mg/m3 of Cr3+ as Cr(NO3)3, to 0.6 mg/m3 of Ni2+ as NiCl2, or to filtered air for 4 months (5 days/week, 6 hr/day). Light microscopy of the lung tissue showed widespread areas with nodular accumulation of macrophages in all rabbits exposed to both metals, in two rabbits exposed to nickel alone, and in none of the controls. Electron microscopy of the lung showed attenuated septa and alveoli stuffed with surfactant-like material in the group exposed to both metals. In two of these rabbits, groups of alveoli were filled with densely packed debris and type I cell borders were obscure. The reaction in the group exposed to nickel alone was less prominent. The volume density of alveolar type II cells showed a fourfold increase after exposure to both metals and a twofold increase following exposure to nickel alone compared to controls. The lung tissue content of total phospholipids and especially phosphatidylcholines and phosphatidylinositols was significantly higher in the groups exposed to both metals than in controls or in animals exposed to nickel only. In lung tissue the molar percentage of 1,2-dipalmitoylphosphatidylcholine was significantly higher in the group exposed to both metals than in the other groups. The results indicate that trivalent chromium potentiates the effect of nickel on the type II cells resulting in an increased surfactant production; in addition, trivalent chromium probably reduces the catabolism of surfactant in alveolar macrophages. Our observations raise the concern that noxious effects might occur also in humans exposed to a combination of nickel and trivalent chromium.

Animals↗

PubMed1989

Tracheobronchial clearance in asthma-discordant monozygotic twins.

Tracheobronchial clearance and bronchial reactivity were studied in 6 asthma-discordant monozygotic twin pairs, and in 3 concordant pairs as controls. Clearance of 6-microns Teflon particles labeled with 99mTc was followed for 2 h. The results indicate that clearance in the larger airways is usually not severely impaired in mild to moderate asthma, and that it may be increased as well as decreased. Bronchial reactivity correlated with clearance in the nonasthmatics.

Administration, Inhalation↗

PubMed1989

Intraphagosomal pH in alveolar macrophages studied with fluorescein-labeled amorphous silica particles.

Intraphagosomal pH in rabbit alveolar macrophages was studied using amorphous silica particles (FSP) and yeast particles (FYP) labeled with fluorescein. The pH was estimated from the quotient between the fluorescence intensity at wavelength 519 nm with excitation at wavelengths 495 and 450 nm. Within a factor of 10, pH was independent of the number of FSP added to macrophages in vitro. In macrophages cultured for 24 h, the pH obtained with FSP and FYP was about 5. Three hours after lavage, pH was the same as after 24 h for the FSP but significantly higher for the FYP, 5.8. Both 3 and 24 h after lavage, more lysosomes were in contact with the FYP-containing phagosomes than with the FSP-containing ones. Most FSP were in tight contact with the phagosomal membrane, while there was a clear zone between most FYP and the phagosomal membrane. The differences in pH and morphology between cells containing FSP and FYP might be explained by the assumptions that the macrophages disintegrate the FYP, which results in higher pH, and that the disintegration of FYP is more efficient at 3 than at 24 h after the lavage. The intraphagosomal pH was lower when the macrophages were allowed to phagocytize the FSP in vivo. The pH values were 5.1 in vitro, 4.9 at 24 h, and 4.5 at 1 week after the FSP had been instilled via trachea. The FSP should be a useful tool for estimation of intraphagosomal pH at basic conditions, i.e., the milieu to which many inhaled inorganic particles will be exposed.

Animals↗