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Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 91 records · Page 5Linked to original sources
PubMed1997

Bronchoalveolar lavage findings in firefighters.

Firefighters are exposed to irritating, asphyxiating toxic gases and aerosols. Previous studies indicate that this may result in acute as well as chronic lung function impairment. It is well known that inhalation of organic material can cause alveolitis. The purpose of this study was to investigate whether firefighters repeatedly exposed to fire gases and other combustion products develop inflammatory changes in the lower airways and, if so, what subtype of cells and soluble components accumulate. Thirteen nonsmoking firefighters underwent bronchoalveolar lavage (BAL), and the results were compared to a reference group of 112 nonsmoking healthy volunteers. The firefighters showed lower recovery of instilled lavage fluid (61% vs 72%; P < 0.01) and an increase in the proportion of lymphocytes in that fluid (8.2% vs 5.7%; P < 0.05). Alveolar macrophage fluorescence, which is a sign of uptake of inhaled fluorescent material, rather than a reflection of the degree of inflammation, was increased in two firefighters. Further, the lavage fluid had higher concentrations of native fibronectin (34.6 vs 22.0 micrograms/L; P < 0.01) and hyaluronic acid (27.7 vs 10.0 micrograms/L; P < 0.05). This may indicate local cell activation, since the alveolar capillary membrane probably was intact, as indicated by an unaffected albumin concentration. The observed changes in the deep airways are probably caused by exposure to smoke. It cannot be concluded whether these changes are permanent or are part of a natural temporary defense mechanism.

Adult↗
PubMed1997

The effects of midazolam and flumazenil on psychomotor function.

STUDY OBJECTIVE: To determine the effects of midazolam and its antagonism with flumazenil on psychomotor function as assessed by the perceptive accuracy test (PAT) and choice reaction time (CRT). DESIGN: Double-blind, cross-over, randomized, placebo-controlled study. SETTING: Department of Anaesthesiology, University Hospital, Linköping, Sweden. SUBJECTS: 11 healthy volunteers (6 females, 5 males, mean age 32 years). INTERVENTIONS: Midazolam 0.1 mg/kg (Group MH), midazolam 0.035 mg/kg (Group ML), or placebo (Group PL) were injected intravenously (IV) in a cross-over design. Flumazenil 0.5 mg was injected after 60 minutes. Plasma concentrations of midazolam were measured at 3, 30, 60 and 75 minutes. MEASUREMENTS AND MAIN RESULTS: Baseline values were first obtained on psychomotor tests including the PAT and CRT. These tests were then repeated 30 and 60 minutes after the IV injection of midazolam or placebo, and repeated 15 and 30 minutes following the injection of flumazenil. A dose-dependent effect of midazolam was seen on the PAT and CRT. Flumazenil completely reversed the psychomotor effects of midazolam in Group ML at 60 minutes but not in Group MH, and this action was clearly detected by the PAT. Psychomotor tests had returned to baseline values when the plasma concentration of midazolam was below 33 ng/ml. A marked inter-individual variation was seen on the PAT, CRT, and in the correlation between the plasma concentration and the results on the PAT. CONCLUSIONS: There was a dose-dependent deterioration in psychomotor performance in subjects given midazolam. The PAT was sensitive in the detection of these residual effects, but a large inter-individual variation in the psychomotor effects of midazolam was evident that could be due to pharmacodynamic and pharmacokinetic variability between individuals. Flumazenil in a dose of 0.5 mg IV completely reversed the effects of low-dose, but not high-dose, midazolam.

Adjuvants, Anesthesia↗
PubMed1997

The effect of early experience on MHC-based mate preferences in two B10.W strains of mice (Mus domesticus).

Previous experiments have demonstrated that mice of some strains show mate preferences that are based on genes of the major histocompatibility complex (MHC), and rearing environment appears to influence these preferences. This experiment investigated if fostering affected MHC-based mate preferences in two additional strains of mice for which it was known that females exhibited MHC-dissimilar preferences. Pups were exchanged between families of B10.GAA37 and B10.CHR51 mouse strains, which differed genetically from one another only at MHC loci. At sexual maturity foster mice were given a choice of two opposite-sex mice of either the foster-family or the foster-mouse MHC type. Preference was based on time spent with each stimulus mouse, the first ejaculation, or the first mount with a stimulus mouse. Although the results were not significant in general, females of the B10.GAA37 strain were mounted first significantly more often by non-foster-family males; first mounts predicted ejaculation preference. The results suggest that rearing environment did affect MHC-based preferences in females of this strain, although learning of self-MHC cues and use of non-MHC cues for mate choice may also occur. These results are compared to those of previous experiments.

Animals↗
PubMed1997

Surfactant prevents quartz induced down-regulation of complement receptor 1 in human granulocytes.

Quartz is known to induce an inflammatory response in the alveolar space by recruitment of different effector cells. We investigated the interaction between granulocytes and quartz with respect to expression of complement receptor type 1 (CR1) and CR3, with and without the presence of surfactant. Granulocytes from hemolyzed blood were stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), which mobilize the intracellular pool of CR1 to the surface, and the mean fluorescence intensity (MFI) measured by cytofluorometry was 47.4 (46-63.6) (median; interquartile range). Quartz exposure reduced the CR1 expression to 23.2 (22.8-30.6) MFI units (P < 0.01), a porcine surfactant preparation added during quartz exposure abolished the down-regulation completely, 47.7 (43.2-62.3) MFI units (P < 0.001). Similar results were obtained after preincubation of the cells with surfactant followed by quartz exposure. No significant influence on CR1 expression was found by a synthetic lipid mixture, nor was the CR3 expression affected. In conclusion, this study demonstrates that the presence of surfactant inhibits quartz induced down-regulation of CR1 on activated granulocytes.

Adolescent↗
PubMed1997

HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis.

Although most patients with sarcoidosis have a good prognosis, a significant proportion runs a more severe and prolonged disease course. There is no marker to distinguish these subpopulations of patients, however. To investigate the relationship between HLA haplotype and clinical course, 122 Scandinavian patients with sarcoidosis were genomically typed for HLA-DR, -DQA1 and -DQB1 alleles using PCR amplification with sequence-specific primers. Control subjects were 250 healthy Swedish volunteers. Patients were carefully clinically monitored for up to 10 yr. We found that HLA-DR17(3) was overrepresented among sarcoidosis patients (33%) compared with control subjects (17%, p < 0.001). Ninety-one patients were followed for more than 2 yr and classified into chronic or nonchronic patients, according to disease outcome. Among the 34 patients with a nonchronic form of sarcoidosis, 65% were DR17(3)-positive (p < 10(-5) versus control subjects). On the other hand, DR14(6) and DR15(2) were significantly associated with chronic disease. Even in patients with clinical manifestations that are normally associated with good prognosis, HLA typing enabled a subgrouping into two categories with significantly different clinical courses. Therefore, HLA class II typing is a valuable tool in predicting the outcome of the disease in Scandinavian sarcoidosis patients.

Adult↗
PubMed1997

Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages.

Alveolar macrophages (AM) and interstitial macrophages (IM) from rat lungs were characterized with respect to morphology, phagocytosis, adhesion properties, and phenotype. AM were recovered by lung lavage and IM by treatment of the lung tissue with DNAse and collagenase. The AM were enzyme treated in the same way as the IM. The IM were smaller than AM and had a higher nuclear to cytoplasm ratio. They had markedly lower phagocytic capacity. The attachment of particles to the cell surface was significantly lower in IM than in AM, but the capacity to ingest the particles was the same. Adherence to vitronectin- as well as fibronectin-coated surfaces was significantly higher in AM. The phagolysosomal pH was similar in IM and AM, around pH 5, indicating that dissolution of inorganic particles can take place effectively also in IM. Five surface receptors were studied, and the expression differed significantly in all five between AM and IM. The expression of OX-1 (CD 45), a common leukocyte antigen, was significantly higher on AM as was the expression of CD 71 (transferrin receptor). The receptor density for OX-42 was higher on a fraction of IM. This might be compatible with a stronger interaction between these cells and, for example, matrix components. IM had more surface antigen expressing MHC class Ia (OX-6) and CD 54. Both receptors are important for the antigen presentation capacity of macrophages. These findings show profound differences in phenotype between AM and IM and indicate that IM is a highly immunocompetent cell and should not be regarded only as a precursor to AM.

Animals↗
PubMed1997

Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non-smokers by NO2.

Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture supernatants were collected 4 h after the exposure and assayed for secreted TNF-alpha, IL-1 beta, IL-8 and MIP-1 alpha. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-alpha and IL-1 beta, but not IL-8 (MIP-1 alpha not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-, 1.5- and 3-fold the amounts of IL-1 beta, IL-8, TNF-alpha and MIP-1 alpha, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration-dependent inhibition of the secretion of all cytokines except IL-1 beta from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-alpha from non-smoker's cells was inhibited by the gas in a concentration-dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-alpha. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1 beta mRNA. However, exposure to the gas inhibited LPS-induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcriptional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.

Adult↗
PubMed1997

Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis.

Patients with extrinsic allergic alveolitis (EAA) have accumulations of T-lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been implicated in the pathogenesis of EAA. The objective of the present study was to analyse the T-cell receptor (TCR) V alpha and V beta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBLs) before and after treatment. Twelve patients with clinical signs of extrinsic allergic alveolitis were studied at disease onset, and nine of the 12 were also studied after treatment and clinical recovery. Lung cells, obtained by bronchoalveolar lavage (BAL), and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V monoclonal antibodies. The changes in TCR V gene usage were most pronounced in BAL CD8+ cells, as compared to the BAL CD4+, PBL CD8+ and PBL CD4+ subsets. At disease onset, 10 of the 12 patients had lung restricted expansions of CD8+ T-cells using a particular V alpha or V beta gene segment, and 8 of the 12 patients had CD8+ T-cell expansions in PBL. For the patients in whom a follow-up was possible, a majority of the expansions in the lungs were normalized, whereas most of the expansions in PBL remained. An over-representation of human leucocyte antigen (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An increased selected T-cell receptor V gene usage may follow specific interactions between T-cells and antigens. In extrinsic allergic alveolitis, we determined that such expansions occur most frequently in the lung CD8+ T-cells. Since most expansions of lung CD8+ T-cells normalized with clinical improvement, these are further implicated in the pathogenesis of extrinsic allergic alveolitis.

Acute Disease↗
PubMed1997

Detection of extrathoracic manifestations in sarcoidosis with somatostatin analogue scintigraphy.

BACKGROUND AND AIM OF WORK: Scintigraphy using a long lived radiolabelled somatostatin analogue [111In-DTPA-D-Phe1]-octreotide (OctreoScan) has previously been shown to be useful in the detection and management of neuroendocrine tumours, as well as in the imaging of various other malignant tumours. It was recently reported that the radiopharmaceutical accumulates also in the granulomatous lesions in Wegener's disease and in sarcoidosis. The present study was undertaken in order to evaluate the usefulness of the technique in detection of extrathoracic manifestations. METHODS: OctreoScan scintigraphy was performed in 5 patients with biopsy-proven sarcoidosis. A patient with a familial history of multiple endocrine neoplasia served as control. RESULTS: In 4/5 patients previously unknown granulomas were registered, and in the remaining subject the findings at the physical examination were confirmed. CONCLUSIONS: We conclude that somatostatin analogue scintigraphy may be helpful in finding extrathoracic granulomatous lesions in sarcoidosis, thus providing good prerequisites for focused biopsy attempts.

Adult↗
PubMed1996

Background and line interference corrections in quantitative GD-OES - New approaches to an old problem.

The origin of radiative background in GD-OES is discussed, in connection with the problem of multi-matrix measurements in depth profile analysis. Backed by some experimental evidence in the form of line scans, it is argued that line emission from sample material and the plasma gas (Ar) make up the dominating contributions to the radiative background. The contribution from Ar, in this work termed Matrix-independent Background (MIB), is investigated in more detail. It is shown that, at constant voltage and current, the Ar emission intensity is nearly constant and independent of the pressure, but somewhat matrix-dependent. It is suggested that the MIB can be expressed as a linear function of the intensity of an Ar reference line. This idea is tested experimentally by making intensity measurements on a large set of calibration standards of varying composition. The results are fitted to a calibration function which allows optional definitions of the MIB. It is shown that with a MIB defined as a linear function of the Ar intensity, the different contributions to the spectral background can be more accurately determined than with the MIB defined as a constant.

Journal Article↗
PubMed1996

Adhesion properties of human alveolar macrophages with respect to extracellular matrix components and chemotactic agonists.

Adherence has an essential impact on the differentiation and activation of tissue dwelling monocytes/macrophages. We have considered the effect of selected chemotactic agonists (fMLP, RANTES, IL-8) on the adhesion properties of human alveolar macrophages prepared by bronchoalveolar lavage. The macrophages were co-incubated in buffer alone or buffer supplemented with respective agonist, for different time points, in culture wells precoated with albumin, vitronectin and fibronectin, respectively. The macrophages displayed a gradual increase in adhesion in all three surfaces and discriminated between the different matrix components, but did not respond to the selected agonists with increased adhesion.

Adult↗
PubMed1996

Transient increases in albumin and hyaluronan in bronchoalveolar lavage fluid after quitting smoking: possible signs of reparative mechanisms.

Inhalation of tobacco smoke results in an accumulation of cells in the lower respiratory tract. The inflammatory response in the alveoli and lung interstitium may also be reflected by increased bronchoalveolar lavage (BAL) fluid concentrations of extracellular matrix components. The present study investigated the influence of smoking on the BAL fluid concentrations of albumin (ALB), hyaluronan (HA) and fibronectin (FN). Lavage fluids from 18 smokers were analysed before and at 1, 3, 6, 9 and 15 months after smoking cessation. Never-smokers (n = 112) served as a reference group. The total cell concentration and the concentrations of macrophages, lymphocytes, neutrophils and eosinophils were higher (P < 0.001-0.01) in smokers' BAL fluid than in never-smokers', but the values returned to normal within 9 months of smoking cessation. The HA concentration was higher (P < 0.001) in smokers' than in never-smokers' BAL fluid, but FN and ALB did not differ. Transient increases in the concentrations of ALB and HA (P < 0.01 for both) was observed within 6 months of smoking cessation. These findings indicate a temporary heightened alveolar-capillary permeability and an increased production and/or degradation of HA, being enhanced following smoking cessation. The findings probably reflect an initiation of a reparative process.

Adult↗
PubMed1996

Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages.

Smoking induces a chronic inflammatory process in the lower respiratory tract, where the alveolar macrophages (AM) are the main phagocytes. In the present study, the expressions of different membrane glycoproteins (CD11abc, CD71, CD54, CD14 and CD16) were determined by flow cytometry in AM from smokers and non-smokers after quenching of the intracellular autofluorescence. The metabolic activity of the AM was quantified as a functional test. The expressions of CD11a, CD54 and CD71 were higher in non-smokers' AM than in smokers'. The expressions of CD11b and CD16 were similar between the groups, while the CD11c was higher in smokers' AM compared with non-smokers'. The expression of CD14 was weak in both groups, therefore there was no clear-cut difference between the background and positively labelled cell populations. The metabolic response after in vitro stimulation with the phorbol ester phorbol myristate acetate (PMA) was higher in non-smokers' than in smokers' AM. Our results indicate that chronic exposure to tobacco smoke influences both the expression of AM membrane antigens and the metabolic activity. AM from non-smokers express a phenotype more related to cell proliferation and an accessory function. In contrast, receptors reflecting adhesion and phagocytosis were unaltered or even increased in smokers' AM. The findings suggest a functional change in the AM population after chronic smoke exposure.

Adolescent↗
PubMed1996

Monocyte and neutrophil adhesion to matrix proteins is selectively enhanced in the presence of inflammatory mediators.

The authors investigated the time course of monocyte and neutrophil adhesion to fibronectin, vitronectin and albumin precoated culture wells, using mixed leucocyte populations from healthy blood donors. Moreover, the influence of chemotactic agonists on the adhesion properties as well as the quantitative expression of CD29, CD11b/CD18 and CD61 was analysed by flow cytometry. Different chemotactic agonists were used representing a classical chemotactic agonist (fMLP), and agonists with a preferential effect on monocytes (RANTES) and neutrophils (IL-8), respectively. The authors found a gradual increase in monocyte and neutrophil adhesion to all three surfaces, reaching a plateau at 15 min of incubation. Adhesion to fibronectin was significantly higher at all time points (5, 15 and 60 min, respectively) compared with vitronectin and albumin in both monocytes and neutrophils. Neutrophil adhesion to vitronectin was significantly lower at 60 min compared with 15 min. Monocyte adhesion to albumin was increased by fMLP and RANTES and to vitronectin also by IL-8. Neutrophil adhesion to albumin and vitronectin was increased by fMLP and IL-8, but not RANTES. The adhesion to fibronectin was not altered by any of the chemotactic agonists used. The quantitative levels of CD11b/CD18, but not CD29 and CD61, was increased by fMLP, but not RANTES nor IL-8. The authors conclude that the adhesion of human monocytes and neutrophils to vitronectin and albumin, but not fibronectin, is selectively enhanced by chemotactic agonists and may contribute to the selective accumulation of different leucocyte subsets at the inflammatory site.

Adolescent↗
PubMed1996

Different percentages of peripheral blood gamma delta + T cells in healthy individuals from different areas of the world.

The frequency of gamma delta + T cells in the peripheral blood of 26 Turkish, 24 Swedish, 35 Japanese and 14 "Asian' (non-Japanese) healthy blood donors and healthy volunteers were investigated by flow cytometry. In the Turkish group, 9.3% (median value) of the CD3+ peripheral blood T cells expressed the gamma delta T cell receptor. A similar level of gamma delta + T cells was found in the non-Japanese "Asian' healthy volunteers (9.2%), while significantly lower values were detected in the Swedish (4.2%) and Japanese (4.5%) groups. These dramatic differences in normally occurring gamma delta + T cells in different groups of healthy individuals were further reflected by a low incidence of > 10% gamma delta + T cells in the Swedish (0/24) and Japanese (6/35) groups compared to the Turkish (12/26) and "Asian' (5/14) groups. The described gamma delta + T cell differences between distinct ethnic groups are thus likely to be a consequence of environmental factors, but additional genetic influences cannot be ruled out. The present study demonstrates the potential importance of the ethnic origin and environmental history of subjects examined in studies of gamma delta + T cells-disease relations.

Adolescent↗
PubMed1996

Transferrin C3 offers protection against smoking-associated lung cancer?

In previous investigations increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects, including cancer. In this investigation transferrin C (TF C) subtypes were studied in lung cancer patients and controls from the Stockholm area in central Sweden. There was a significant difference between patients and controls with respect to the distribution of TF C alleles and genotypes, which was mainly due to a low frequency of the TF C3 allele among the patients (P = 3 x 10(-6). However, in adenocarcinoma the frequency of TF C3 types was almost identical to that among the controls, whereas in the smoking-related (squamous and small cell) tumor types the TF C3 frequency was remarkably low (OR = 0.03, 95% CI = 0.00-0.22). Thus individuals with the TF C3 variant appear to enjoy an almost complete protection against smoking-related lung cancer. The frequency of individuals carrying the protective TF C3 variant is approximately 17% in central Sweden and 25% in Finland, which has the highest TF C3 frequency found so far. The mechanism behind the observed association, which appears to be independent of iron binding and body iron stores, remains to be elucidated.

Adenocarcinoma↗