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Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 109 records · Page 6Linked to original sources
PubMed1996

Inhibitory effect of gastrin peptides on triacylglycerol secretion in Hep G2 cells.

OBJECTIVES: To determine whether human liver cells respond to gastrin peptides by reducing their secretion of triacylglycerols, as recently observed in rat hepatocytes. DESIGN: Cells of the human hepatoblastoma cell line Hep G2 were incubated with pentagastrin and heptadeca gastrin, followed by lipid analysis of media and cells. METHODS: Cultivation of cells; analyses of triacylglycerols, cholesterol and protein; statistical analysis. RESULTS: As the secretion of triacylglycerols in Hep G2 cells incubated with basal medium (Eagle's minimum essential medium with non-essential amino acids, penicillin, streptomycin and glutamine) is only about 20% of the triacylglycerol secretion reported for human liver cells, the possibility of detecting statistically significant effects of gastrin peptides on lipid secretion is reduced compared to the situation in normal hepatocytes. However, by a combined addition of 0.1 mmol/l albumin-bound oleate, 10 mmol/l sodium butyrate and 0.1 mg/ml dextran sulphate to the basal medium, the triacylglycerol secretion in Hep G2 cells was found to be more than twice as high as in cells incubated with basal medium alone. With this supplemented medium a biphasic concentration-dependent statistically significant inhibitory effect of both pentagastrin and heptadeca gastrin on triacylglycerol secretion in Hep G2 cells was demonstrated. CONCLUSION: These results indicate that gastrin peptides may play a role in the regulation of lipoprotein secretion in human liver cells.

Culture Media↗
PubMed1996

The immotile cilia syndrome: characterization of the inflammatory response in nonsmoking patients with dysfunction of the cilia.

In order to demonstrate how patients with immotile cilia syndrome (ICS) are associated with lower respiratory tract inflammation, bronchoscopy and fractionated BAL were performed on eight ICS patients. Their VC was 84.5 +/- 16.7% (mean +/- SD) and FEV1 73.1 +/- 19.9% of predicted. Endobronchial signs of bronchitis were observed in all patients. The total cell concentrations in the BAL fluid were increased, compared to healthy nonsmokers (n = 10), both in the bronchial (BP) and alveolar portion (AP) (p < 0.01 for both). In the BP, this was mainly due to a high concentration of neutrophils (p < 0.001), whereas in the AP, the concentrations of lymphocytes (p < 0.01) as well as all types of granulocytes (p < 0.001-0.01) were elevated. The signs of active inflammation in the lower respiratory tract were confirmed by the concomitantly elevated (p < 0.001-0.05) concentrations of the soluble BAL components albumin, fibronectin and hyaluronan. Thus, the inflammatory response is not restricted to the ciliated conducting airways, but also occurs in the alveolar space and results-surprisingly-in only a slightly impaired lung function.

Adult↗
PubMed1996

Sarcoidosis and regional enteritis in two patients.

Both sarcoidosis and Crohn's disease (regional enteritis) are characterized by granuloma formation and they also have an unknown etiology. Only a few subjects with co-existing sarcoidosis and Crohn's disease have been reported in the literature. We report two cases who suffered from both disorders. In the two subjects Crohn's disease began first and the symptoms of sarcoidosis came later; four and sixteen years, respectively.

Adolescent↗
PubMed1995

Up-regulation of antigens on alveolar macrophages in quartz exposed rats.

We have analysed the expression of the OX-6 and OX-42 antigens on alveolar macrophages in rats after intratracheal exposure to quartz. Eight female Sprague Dawley rats were included in the study. Four were exposed to physiological saline and four to quartz dust. The rats were sacrificed after 58 +/- 2 weeks and alveolar macrophages were harvested and analysed by flow cytometry. We found a significant higher amount of both antigens on alveolar macrophages harvested from quartz exposed rats. However, we did not find any significant difference in the percentage positive labeled cells between the two groups. We conclude that quartz dust induces up-regulation of functional receptors on alveolar macrophages in rats and that quantitative analysis of these receptors may serve as inflammatory markers in the bronchoalveolar space.

Animals↗
PubMed1995

Sarcoidosis patients have bronchial hyperreactivity and signs of mast cell activation in their bronchoalveolar lavage.

An increased (p < 0.001) frequency of bronchial hyperreactivity (BHR) was found in sarcoidosis patients as compared with healthy volunteers. The patients had more mast cells (p < 0.001) and tryptase (p < 0.001) in their bronchoalveolar lavage fluid, but there were no differences between BHR-positive and BHR-negative patients. Furthermore, the bronchoalveolar lavage fluid concentrations of macrophages, lymphocytes, and of the soluble components albumin, fibronectin, and vitronectin were also elevated in the sarcoidosis patients, indicating an ongoing inflammation in the airways and/or in the interstitium. We observed no significant differences in the parameters when the sarcoidosis patients were subdivided into BHR, clinical activity, or chest X-ray stages. Our findings may indicate a multifactorial background to the hyperreactivity.

Adolescent↗
PubMed1995

A possible alteration of surfactant in broncho-alveolar lavage fluid from healthy smokers compared to non-smokers and patients with sarcoidosis.

In disorders affecting the alveoli and lung interstitium and altered composition of the epithelial lining fluid, i.e. the surfactant, may affect the outcome of the disease. The phospholipid composition in bronchoalveolar lavage (BAL) fluid was determined in healthy non-smoking (n = 8) and smoking (n = 12) volunteers, and in non-smoking patients with clinically active sarcoidosis (n = 7). The total amount of phosphatidylcholines (median +/- SD) were in the non-smoking control group (21.8 +/- 5.7 mumol/L) and in the non-smoking sarcoidosis group (26.1 +/- 9.1 mumol/L), while healthy smokers had significantly (p < 0.05 for both) lower amounts (14.6 +/- 5.6 mumol/L). The composition of phosphatidylcholines was similar in all three groups with one exception. Palmitoylmyristoyl-phosphatidylcholine constituted a significantly higher fraction among the smokers (12.7 +/- 2.1 mol%) compared to the non-smoking control group (10.6 +/- 1.4 mol%; p < 0.05) and the sarcoidosis group (10.6 +/- 0.6 mol%; p < 0.01). In conclusion, no quantitative or qualitative differences in phosphatidylcholines were observed between non-smoking healthy volunteers and non-smoking patients with clinically active sarcoidosis. However, in smoking healthy volunteers the total amount of phosphatidylcholines was reduced and their composition altered. Earlier reported conflicting results may be due to the fact that the smoking habits have not been considered.

Adolescent↗
PubMed1995

Restricted usage of T cell receptor V alpha/J alpha gene segments with different nucleotide but identical amino acid sequences in HLA-DR3+ sarcoidosis patients.

BACKGROUND: Sarcoidosis is a granulomatous disease characterized by the accumulation of activated T cells in the lungs. We previously showed that sarcoidosis patients expressing the HLA haplotype DR3(17),DQ2 had increased numbers of lung CD4+ T cells using the T cell receptor (TCR) variable region (V) alpha 2.3 gene segment product. In the present study, the composition of both the TCR alpha- and beta-chains of the expanded CD4+ lung T cells from four DR3(17),DQ2+ sarcoidosis patients was examined. MATERIALS AND METHODS: TCR alpha-chains were analyzed by cDNA cloning and nucleotide sequencing. TCR beta-chains were analyzed for V beta usage by flow cytometry using TCR V-specific monoclonal antibodies or by the polymerase chain reaction (PCR) using V beta- and C beta-specific primers. J beta usage was analyzed by Southern blotting of PCR products and subsequent hybridization with radiolabeled J beta-specific probes. RESULTS: Evidence of biased J alpha gene segment usage by the alpha-chains of V alpha 2.3+ CD4+ lung T cells was found in four out of four patients. Both different alpha-chain nucleotide sequences coding for identical amino acid sequences and a number of identically repeated alpha-chain sequences were identified. In contrast, the TCR beta-chains of FACS-sorted V alpha 2.3+ CD4+ lung T cells were found, with one exception, to have a nonrestricted TCR V beta usage. CONCLUSIONS: The finding of V alpha 2.3+ CD4+ lung T cells with identical TCR alpha-chain amino acid sequences but with different nucleotide sequences strongly suggests that different T cell clones have been selected to interact with a specific sarcoidosis associated antigen(s). The identification of T cells with restricted TCR usage, which may play an important role in the development of sarcoidosis, and the possibility of selectively manipulating these cells should have important implications for the treatment of the disease.

Adult↗
PubMed1994

T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.

Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4+ T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4+ and CD8+ lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V alpha 2.3+ CD4+ lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V alpha/V beta gene products analyzed in this study--V alpha 12, V beta 2, V beta 3, V beta 5.1, V beta 5.2/5.3, V beta 5.3, V beta 6.7, V beta 8.1, and V beta 12--were in general normally expressed by CD4+ T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3+ patients and found an association between the ratio bronchoalveolar lavage fluid/peripheral blood V alpha 2.3+ CD4+ T cells and clinical signs of disease activity. Finally, when analyzing TCR V gene usage by CD8+ bronchoalveolar lavage fluid and peripheral blood T cells, a normal V alpha 2.3 usage was found in all cases, but lung-restricted T-cell expansions using other TCR V gene segment products were identified.

Adult↗
PubMed1994

Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages.

Monocyte/macrophages adhere to cells (lymphocytes, vascular endothelial and other cell types) and to extracellular matrix components (fibronectin and laminin) by using specific cell surface adhesive structures. In the present study we have analyzed expression of integrins, immunoglobulin (Ig)-related, selectins, and other adhesion molecules on blood monocytes, in vitro differentiated macrophages (ivMs), and alveolar macrophages (AMs), obtained from healthy nonsmokers by bronchoalveolar lavage (BAL). We have also investigated expression of adhesion molecules on myelomonocytic cell lines HL-60, THP-1, KG-1, and U937 before and after tetradecanoyl phorbol acetate (TPA)-induced differentiation. With regard to the integrin family, monocytes expressed beta 1 (CD29), alpha 4, alpha 5, alpha 6, beta 2 (CD18), CD11a, CD11b, and CD11c subunits, but not alpha V (CD51). Some reactivity with mAbs against the platelet antigens CD41b (IIb) and CD61 (beta 3) was detected. The Ig-related molecules CD54 (ICAM-1), ICAM-2, and CD58 (LFA-3) were expressed, as well as L-selectin and the carbohydrate ligands Le(x) (CD15) and sialyl Le(x). Immunolabeling for the structurally unrelated molecules CD44 and CD36 was strongly positive. In comparison to monocytes, AMs showed much lower expression of alpha 4, alpha 6, beta 2, CD11a, CD11b, L-selectin, Le(x), and sialyl Le(x). Moreover, ICAM-2 and CD36 were practically absent whereas expression of alpha 3, but not of CD11c, was higher. Similar results were obtained with ivMs. All four myelomonocytic cell lines showed down-regulation of alpha 4 and up-regulation of CD11c after TPA treatment. These findings indicate that maturation of monocytes into macrophages is accompanied by characteristic changes in adhesion molecule expression. The particular array of adhesion molecules on monocytes and macrophages may account for differences in the functional properties of these cells.

Antigens, CD↗
PubMed1994

Sawdust-induced inflammatory changes in rat lung: effects on alveolar and interstitial cells in relation to time.

Exposure to sawdust and its contaminants, e.g., terpenes, may cause respiratory tract and lung parenchymal inflammation. To monitor these changes over time. Sprague-Dawley rats were exposed at one occasion to 2.5 mg sawdust or saline by intratracheal instillation. Flow cytometry analyses were done on bronchoalveolar lavage (BAL) cells. Lung tissue specimens were analyzed histologically and immunohistochemically. After one week, the number of BAL polymorphonuclear leukocytes was increased (P < 0.05, N = 8), followed at six weeks by increases of macrophages and lymphocytes (both P < 0.01, N = 8). Enhanced expressions of class II antigens and complement receptors on macrophages after one week were even more pronounced at six weeks, indicating cellular activation. The BAL findings, also including increased (P < 0.001, N = 8) concentrations of hyaluronan with progressing changes over time, confirmed the signs of inflammation, as did the histological analysis of the lung tissue specimens with an accumulation of polymorphonuclears, macrophages, and hyaluronan in the interstitium.

Animals↗
PubMed1994

Phagolysosomal pH in alveolar macrophages from smokers and non-smokers.

1. Alveolar macrophages efficiently phagocytize particles deposited in the alveolar part of the lung. Phagolysosomal pH in alveolar macrophages from rabbits, dogs, baboons and guinea pigs is around 5 pH units. A low pH is of importance for clearance of inorganic particles and probably also for defence against bacteria and fungi. 2. Phagolysosomal pH in alveolar macrophages from smokers and non-smokers was measured using fluorescein-conjugated amorphous silica particles as a probe. pH was the same in both groups and similar to earlier studies on alveolar macrophages from animals. 3. The morphological picture between alveolar macrophages from smokers and non-smokers differed clearly with a high number of dense inclusions of great variation in size and shape in macrophages from smokers. Ingested test particles were located in all types of inclusions. 4. We conclude that phagolysosomal pH in human alveolar macrophages is similar to that in several animal species and that it is rather insensitive to influence from the environment.

Adult↗
PubMed1993

Controlled short-time terpene exposure induces an increase of the macrophages and the mast cells in bronchoalveolar lavage fluid.

Eight healthy nonsmoking volunteers underwent terpene exposure (450 mg/m3 air) on 4 different occasions within a 2 week period. Total exposure time was 12 hours. Before and after the sequences of exposure, bronchoalveolar lavage was performed. Twenty hours after the exposure there was a significant (p < 0.05) increase of the alveolar cell concentration (median pre-exposure value 76 x 10(6) cells/L, post-exposure value 126 x 10(6) cells/L), predominantly due to an increment of the macrophages (from 72 x 10(6) cells/L to 121 x 10(6) cells/L). The mast cells also increased from 1/10 to 5/10 visual fields. No elevated concentrations of albumin, fibronectin, hyaluronan (hyaluronic acid), and tryptase were observed. We conclude that terpene exposure, in a concentration regarded as moderate, induces an acute alveolar cellular reaction in healthy subjects.

Adult↗