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Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 73 records · Page 4Linked to original sources
PubMed1999

A catheter tactile sensor for measuring hardness of soft tissue: measurement in a silicone model and in an in vitro human prostate model.

Tissue hardness is related to tissue composition, and this is often changed by disease. It is therefore of interest to measure the hardness in an objective and non-invasive way. A tactile sensor based on a vibrating piezoelectric ceramic element in a feedback loop is described. When the sensor touches an object it produces a frequency shift related to the hardness of the object. The aim of this study was to develop an in vitro hardness measurement method using a catheter type version of the sensor. The method was evaluated in an established silicone tissue model and on human prostate tissue in vitro. A linear relationship was found with a high degree of explanation (R2 = 0.98) between a cone penetration hardness standard (DIN ISO 2137) applied to the silicone model and the corresponding frequency shift. The results from measurements on a human prostate tissue sample, fixed with formalin, showed that the relative hardness measured with the tactile sensor correlated (R = -0.96, p < 0.001, N = 60) with the proposed hardness related to the histological composition of the prostate tissue. The results indicated that hardness of prostate tissue, and maybe hardness of human tissue in general, can be expressed according to the cone penetration standard and that the hardness can be measured with this tactile sensory system. These findings hold the promise of further development of a non-invasive tool for hardness measurement in a clinical situation.

Aged↗
PubMed1999

Lysophosphatidylcholine abrogates the CR1 preserving effect of surfactant on quartz-exposed human granulocytes.

The effects of pulmonary surfactant on granulocytes were studied by flow cytofluorometry. Cells from hemolyzed blood were first activated by N-formylmethionyl-leucyl-phenylalanine (fMLP) which mobilizes complement receptor 1 (CR1) from the intracellular pool to the cell surface. The reduced CR1 expression observed after quartz incubation was abolished by a porcine surfactant preparation containing phospholipids and the hydrophobic surfactant proteins. Phospholipids alone had no preservative capacity. However, addition of the surfactant proteins to the phospholipids did not restore the CR1 values to that of intact surfactant, probably due to changed protein structure during the purification procedure. Heating of surfactant at 37 degrees C up to 72 h reduced the preservative effect of surfactant on CR1 expression. Congruent results of CR1 expression were achieved when 1-10% lysophosphatidylcholine was added to the surfactant preparations. Our results imply that lysophosphatidylcholine formed during storage of surfactant at elevated temperatures influences CR1 expression on granulocytes.

Granulocytes↗
PubMed1999

Airway inflammation and altered alveolar macrophage phenotype pattern after repeated low-dose allergen exposure of atopic asthmatic subjects.

BACKGROUND: The alveolar macrophage (AM) constitutes an important link between pulmonary innate and adaptive immunity due to its antigen-presenting capacity and ability to express different immunomodulating mediators. The role of AMs in the pathogenesis of allergic inflammation has yet to be fully determined. OBJECTIVE: To investigate clinical effects and any change in the AM phenotype pattern after inhalation of sub-clinical doses of allergen by asthmatic patients. METHODS: Eight subjects with allergic asthma underwent repeated low-dose allergen provocations equivalent to 10% of PD20. AMs recovered with bronchoalveolar lavage (BAL) were characterized by flow cytometric analysis of adhesion molecules, co-stimulatory molecules and markers for AM population activation and heterogeneity. RESULTS: An allergic airway inflammation, sub-clinical in six out of eight subjects, was obtained after low-dose allergen provocations, as determined by increased airway methacholine reactivity, increased BAL fluid total cell and eosinophil counts and increased serum ECP levels. The AMs showed a post-challenge altered phenotype pattern with a decreased expression of CD11a, CD16, CD71 and HLA class I and an increased expression of CD11b and CD14. The AMs were positive for CD83 and a weak post-challenge increase in the CD83 expression was found. CONCLUSION: Repeated low-dose allergen exposure induces an allergic airway inflammation in asthmatic subjects. The inflammation is associated with an altered AM phenotype pattern, consistent with an influx of monocytes and a hypothetical increased accessory cell function in the airways, possibly contributing to the development and sustenance of airway inflammation in asthma.

Adult↗
PubMed1999

Bronchoalveolar lavage cells from sarcoidosis patients and healthy controls can efficiently present antigens.

OBJECTIVES: The interaction between antigen-presenting cells (APC) and T lymphocytes, that recognize the antigen-HLA complex using its T cell-receptor for antigen, is of crucial importance for a subsequent specific immune response. In patients with pulmonary sarcoidosis, the local antigen-presenting capacity in the lungs has been suggested to be abnormally enhanced, and implicated in the immunopathogenesis of the disease. This study was aimed at increasing the understanding of the capacity to present antigens by APC in the lung compartment. DESIGN AND SUBJECTS: We used bronchoalveolar lavage (BAL) cells and paired peripheral blood mononuclear cells (PBMC) of six sarcoidosis patients and two healthy controls to stimulate in total eight well characterized T-cell clones with known HLA and antigen specificities. All subjects were HLA typed. RESULTS: BAL cells of sarcoidosis patients as well as of healthy controls efficiently induced proliferation of the relevant T-cell clone in an HLA-restricted manner when adding either intact antigen or antigenic peptides. CONCLUSIONS: BAL cells have the capacity to process and present antigens adequately, irrespective of whether they are derived from healthy individuals or from patients with sarcoidosis, implying the alveolar space as an important location for active immune reactions.

Adult↗
PubMed1999

Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis.

BACKGROUND: The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. To gain a better understanding of this process the expression by these cells of cell surface activation markers, co-stimulatory molecules, and adhesion molecules was analysed. METHODS: CD4+ and CD8+ T lymphocytes from peripheral blood (PBL) or bronchoalveolar lavage (BAL) fluid, as well as paired peripheral blood monocytes and alveolar macrophages from 27 patients with sarcoidosis were analysed by flow cytometry. RESULTS: CD26, CD54, CD69, CD95, and gp240 were all overexpressed in T cells from BAL fluid compared with those from PBL in both the CD4+ and CD8+ subsets, while CD57 was overexpressed only in BAL CD4+ cells. In contrast, CD28 tended to be underexpressed in the BAL T cells. Monocyte/macrophage markers included CD11a, CD11b, CD11c, CD14, CD16, CD54, CD71, CD80 and CD86 and HLA class II. CD11a expression in alveolar macrophages (and peripheral blood monocytes) was increased in patients with active disease and correlated positively with the percentage of BAL lymphocytes. Expression of CD80 in macrophages correlated with the BAL CD4/CD8 ratio. CONCLUSIONS: Our data indicate substantial activation of both CD4+ and CD8+ lung T cells in sarcoidosis. There were also increased numbers of BAL lymphocytes whose phenotypic characteristics have earlier been associated with clonally expanded, replicatively senescent cells of the Th1 type.

Abatacept↗
PubMed1999

Antibacterial components in bronchoalveolar lavage fluid from healthy individuals and sarcoidosis patients.

Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, alpha-defensins are mainly bactericidal effectors in circulating granulocytes, beta-defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar lavage fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, alpha-defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway mucosa. In conclusion, the airway epithelium is protected by a complex antibacterial defense system. This is activated in sarcoidosis, and may explain why these patients seldom develop severe respiratory tract infections.

Adult↗
PubMed1999

Increased risk for cancer following sarcoidosis.

Little is known about the cancer risk following sarcoidosis. In a retrospective cohort study, we tested the hypothesis of an increased risk for malignant lymphomas, lung cancer as well as cancer in other organs frequently involved in sarcoidosis. Four hundred seventy-four patients from an incidence study 1966-1980 and 8,541 patients identified in the Swedish Inpatient Register (IPR) 1964-1994 were linked to the Cancer Register, the Register of Causes of Death, and the Register of Total Population. Relative risks were estimated using standardized incidence ratios (SIR). The overall relative risks for cancer were similar and elevated in both cohorts (IPR presented), SIR = 1.3; 95% confidence interval (CI) 1.2 to 1.4. For lung cancer and non-Hodgkin's lymphoma, the relative risk was doubled during the first decade of follow-up. Thereafter, the risk for lung cancer was significantly decreased whereas the risk for non-Hodgkin's lymphoma equaled unity. Throughout follow-up, elevated risks were found for melanoma (SIR = 1.6; 95% CI 1.0 to 2.3) and nonmelanoma skin cancer (SIR = 2.8; 95% CI 2.0 to 3.8). An increased risk was also found for liver cancer (SIR = 1.4; 95% CI 0.8 to 2.2). Thus, sarcoidosis appears to be associated with a significantly increased risk for cancer in affected organs. Chronic inflammation is a putative mediator of this risk.

Adult↗
PubMed1998

Smoking alters the phenotype of macrophages in induced sputum.

To investigate the effect of chronic smoke exposure on pulmonary macrophages (PM), the expression of seven different surface and intracellular molecules of PM was studied in induced sputum (IS) samples from healthy volunteers--nine smokers and seven non-smokers. Sputum was induced by inhalation of nebulized saline (3.5% NaCl). Cell viability and total cell counts (TCC) were performed immediately. Cell differentials were determined on May-Grunwald Giemsa-stained cytospin preparations. The PM were immunologically characterized by use of the following monoclonal antibodies: RFD1, RFD7, CD11b, CD54, CD68, CD71 and HLA-DR. The stainings were performed with a three-step, indirect immuno-alkaline phosphate method. Viability and TCC did not differ between the groups. Smokers had a higher percentage of macrophages (P < 0.05) and a lower proportion of neutrophils (P < 0.05). The percentage of macrophages expressing RFD1, HLA-DR, CD71 (P < 0.01 for all) and CD54 (P < 0.05) was significantly lower in smokers, whereas the remaining markers were expressed equally in the two groups. The results indicate that smoking induces a decrease in the expression by PM of surface molecules known to be associated with the antigen-presenting function.

Adult↗
PubMed1998

The conventionally ventilated operating theatre and air contamination control during cardiac surgery--bacteriological and particulate matter control garment options for low level contamination.

OBJECTIVE: The purpose of the study was to compare the usefulness of a conventional bacteriological technique with that of particle counting under lower air contamination and better aseptic conditions achieved with special staff garments and covering for the patient. Contamination levels were estimated with continuous on line air particle counting measurement, volumetric intermittent short period aerobic bacteriological cultures and wound surface contact cultures. METHODS: In a series of 66 consecutive coronary artery bypass operations performed by the same team and in the same theatre using different types of patient and staff clothing, the impact of a reduced bacteriological and particulate contamination were assessed. The volumetric air contamination of particles > or =5 microm and bacteria-carrying particles were monitored 30 cm above the sternal wound. The bacterial contamination and bacterial wound infections in the sternal and leg wounds were assessed as well. RESULTS: With the alternative garment and textile system, the air counts fell from 25 colony-forming units (CFU)/m3 to 7 CFU/m3 (P < 0.0038). The contamination of the sternal wound was reduced by 46% and that of the leg wound by >90%. In order to give continuous contamination feedback during the whole operation to the theatre staff, particle counts > or =5 microm were monitored and visualized. Air particle counts decreased rapidly from 850 particles/m3 and stabilized to approximately 50 particles/m3 when the alternative clothing system was used (P < 0.001). Low particle counts > or =5 microm should offer the possibility to indirectly estimate air bacteria carrying particle counts during the entire operation. Less than 20% of the total count in this size group carries bacteria. The low air contamination was achieved even in an ordinary ventilated theatre when individual team members used clean air suits in combination with impermeable patient drapes. When air particle level < or =50 particles/m3 is reached, the bacterial air contamination is in the order of that of orthopaedic hip operations. The staff must during the entire operation adjust their activity to air asepsis. CONCLUSIONS: The use of clean air suits and impermeable patient clothing results in a low exogenous contamination of air and wound. Continuous air particle monitoring is a good intraoperative method to monitor the air contamination longitudinally in an operating theatre.

Air Microbiology↗
PubMed1998

Selective CD8+ T cells accumulate in the lungs of patients with allergic asthma after allergen bronchoprovocation.

Our objective was to study whether CD4+ or CD8+ T cells expressing particular T cell receptors (TCR) would accumulate in the lungs of patients with allergic asthma following allergen exposure. We thus analysed the TCR Valpha and Vbeta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBL) of eight patients with allergic asthma before and 4 days after inhalation challenge with the relevant allergen. Lung cells obtained by bronchoalveolar lavage (BAL) and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V-specific monoclonal antibodies that encompass = 50% of the T cell repertoire. Lung-limited T cell expansions were recorded in both the CD4+ and the CD8+ subsets. In BAL CD8+, out of a total of 126 analyses, the number of T cell expansions increased from two to 11 after challenge, some of them dramatic. In BAL CD4+ the frequency of expansions was moderately increased already before challenge, but remained unchanged. A few expansions that tended to persist were noted in PBL CD8+. When analysing the overall change in TCR V gene usage the largest changes were also recorded in the BAL CD8+ subset. Specific interactions between T cells and antigens may lead to an increased frequency of T cells using selected TCR V gene segments. In this study we demonstrate that following allergen bronchoprovocation in allergic asthmatic subjects, T cell expansions preferentially emerge in the lung CD8+ T cell subset.

Adult↗
PubMed1998

The lymphocytic alveolitis in sarcoidosis is associated with increased amounts of soluble and cell-bound adhesion molecules in bronchoalveolar lavage fluid and serum.

OBJECTIVES: Pulmonary sarcoidosis is a chronic inflammatory disorder of unknown aetiology accompanied by a lymphocytic alveolitis. It is likely that a selective and temporal expression of adhesion molecules plays a crucial role in the recruitment of cells to the inflammatory site. We investigated the expression of adhesion molecules on alveolar T-lymphocytes and in bronchoalveolar lavage (BAL) fluid and serum to elucidate mechanisms behind the accumulation of cells in the lung in sarcoidosis. DESIGN: In a cross-sectional study in patients with active and inactive sarcoidosis and in healthy volunteers, we examined, in serum and in BAL fluid, the soluble adhesion molecules, VCAM-1, ICAM-1, and P-, E- and L-selectin. In addition, the expressions of alpha4-beta1 (VLA-4) and alpha5-beta1 (VLA-5) integrins on alveolar T-lymphocytes were analysed. SETTING: The subjects attended the outpatient clinic at the Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Nineteen sarcoidosis patients, nine with clinically active disease, and 13 healthy volunteers were included in the study. The sarcoidosis diagnosis was based on a typical histological and/or clinical (symptoms, radiograph, lung function) picture. RESULTS: In sarcoidosis patients, particularly in those with active disease, an increase of the expressions of beta1-integrins was accompanied by elevated concentrations in BAL fluid of soluble VCAM-1. In serum, the levels of E-selectin and ICAM-1 were significantly higher in patients with active disease than in those with inactive disease and controls. CONCLUSIONS: The findings offer some mechanistic explanations as to how the cell-rich alveolitis in sarcoidosis occurs, and furthermore suggest additional markers, such as s-ICAM-1, for assessment of disease activity.

Adult↗
PubMed1998

Elutriation of human alveolar macrophages: influence on cell surface receptor expression.

Centrifugal elutriation has turned out to be a quick and easy to handle method to separate alveolar macrophages with high purity in bronchoalveolar lavage fluid. However, less is known about the influence of elutriation on the expression of cell surface receptors and cell function. We investigated whether the elutriation procedure or different temperatures affect the expression of some surface receptors. These were selected to reflect different aspects of cell function such as phagocytosis (Fc gamma-receptor), antigen presentation (HLA-DR) and proliferation (transferrin receptor). We conclude that the centrifugal elutriation procedure has no influence on the expression of these functional receptors on resting alveolar macrophages. Heat stimulation, however, increased the expression of HLA-DR and the transferrin receptors. Summarizing, when working with alveolar cells at +4 degrees C elutriation is a quick method which yields a high purity of macrophages that are phenotypically unaltered.

Adult↗
PubMed1998

Differences between rat alveolar and interstitial macrophages 5 wk after quartz exposure.

Macrophages play an essential role in pulmonary host defense. We investigated differences between rat alveolar (AM) and interstitial (IM) macrophages after exposure in vivo to quartz, an inducer of intensive alveolitis. Rats were exposed to 0.5 ml of saline without (n = 8) or with (n = 8) 10 mg of quartz by intratracheal instillation. In a third group (n = 8), 10 mg of surfactant were added to the quartz mixture. Five weeks later, AM were recovered by bronchoalveolar lavage and IM by mechanical fragmentation of the lung, followed by enzymatic treatment. Contamination of AM to the IM fraction was calculated to be 12-15%. After quartz exposure, the expression of major histocompatibility complex class Ia was increased in both AM and IM fractions. The receptor corresponding to human complement receptor 3 increased in AM after quartz exposure, and AM from quartz-exposed animals had a lower metabolic activation. Our findings indicate that IM are immunocompetent cells and that differences between AM and IM fractions occur upon quartz-induced inflammation. This response is not affected by addition of surfactant.

Animals↗
PubMed1998

Evidence for mast cell activation during exercise-induced bronchoconstriction.

Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Twelve nonsmoking subjects with mild asthma and a history of exercise-induced bronchoconstriction exercised on a stationary bicycle ergometer for 5 min at 80% maximum work load. Pulmonary function was monitored and urine was collected before and 30 and 90 min after the provocation. The urinary concentrations of the mast cell markers 9alpha,11beta-prostaglandin (PG)F2 and Ntau-methylhistamine, as well as leukotriene E4 (LTE4) were determined by immunoassay. Seven of the 12 subjects (responders) experienced bronchoconstriction (>15% fall in the forced expiratory volume in one second) following exercise, whereas the pulmonary function of the remaining five subjects (nonresponders) remained stable. The urinary excretion (mean+/-SE) of 9alpha,11beta-PGF2 in the responders increased significantly compared with the nonresponders at 30 (77.1+/-14.4 versus 37.2+/-5.6; p<0.05) and 90 min (79.3+/-8.6 versus 40.4+/-8.5, p<0.05) after exercise challenge. The urinary excretion of Ntau-methylhistamine and LTE4 was not significantly different between the two groups at 30 or 90 min after exercise. The findings represent the first documentation of increased urinary levels of 9alpha,11beta-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced bronchoconstriction in asthmatics.

Adult↗
PubMed1998

Leukocyte counts and macrophage phenotypes in induced sputum and bronchoalveolar lavage fluid from normal subjects.

It is unclear whether leukocytes in induced sputum (IS) and bronchoalveolar lavage (BAL) represent the same cell populations. To compare leukocyte counts and macrophage phenotypes and investigate any measurable dithiothreitol (DTT)-mediated effect on macrophage immunocytochemical staining results, IS and BAL samples from nine healthy smokers and seven nonsmokers were examined. BAL and IS samples were processed and cell viability and cell counts were assessed. The macrophages were characterized by seven monoclonal antibodies (RFD1, RFD7, CD11b, CD54, CD68, CD71 and HLA-DR) using an indirect immunoalkaline phosphatase method. Intraindividual comparison of IS and BAL showed that IS samples from smokers and nonsmokers contained a lower total cell count (p<0.01 smokers, p<0.05 nonsmokers), a lower percentage of macrophages (both p<0.05) and a higher percentage of neutrophils (both p<0.05) than BAL samples. In addition, nonsmokers sputum samples contained a lower proportion of lymphocytes (p<0.05) than BAL. The macrophage expression of RFD7 and CD71 was higher in smokers sputum samples (both p<0.05) than in BAL, while nonsmokers sputum macrophages showed a higher expression of CD54 and CD71 (both p<0.05) than BAL macrophages. DTT-incubated BAL samples showed no difference in macrophage antigen expression from BAL samples not exposed to DTT. In conclusion, the relative proportions of leukocytes and the macrophage phenotypes differed between induced sputum and bronchoalveolar lavage suggesting that the methods provide samples from different lung compartments, inhabited by cells with different phenotypes.

Adult↗
PubMed1997

Covalent binding of proteins to grafted plastic surfaces suitable for immunoassays. II. Picograms of IgE detected in BAL fluid in sarcoidosis.

An ELISA is described for the quantitation of minute amounts of human IgE using microtiter strips which were surface modified according to a procedure previously described. This ELISA used an IgG fraction of a rabbit polyclonal anti-IgE antibody coupled to the carboxylated surface, which prior to coupling had been preactivated with a water soluble carbodiimide. A biotinylated affinity purified rabbit anti-IgE antibody was used together with streptavidin conjugated alkaline phosphatase and biotinylated enzyme for the detection of bound analyte. Sarcoidosis is a systemic disorder of as yet unknown cause with epithelioid granuloma formation in the lung as a prominent feature. With the bronchoalveolar lavage technique, epithelial lining fluid was obtained and analyzed for IgE content since differences of immunoglobulin concentration in bronchoalveolar lavage fluid (BALF) may reflect disease activity. Our modified ELISA system was used for measuring IgE in BALF from healthy controls and sarcoid patients. The assay using modified strips demonstrated a considerably improved sensitivity compared to the use of physical adsorption of first antibody to untreated strips. The detection limit of the improved assay was approximately 3 pg IgE/sample (100 microl). Quantitative recovery of IgE was demonstrated within the measuring range (51.2-12500 pg IgE/ml) and more than 40% (23/54) of the sarcoid patients showed values above the lowest standard concentration (51.2 pg/ml). In contrast, none of the healthy controls (0/22) had detectable IgE as defined by the detection limit of the assay.

Adult↗