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Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 181 records · Page 10Linked to original sources

Comparison of bronchoalveolar lavage fluid recovered during bronchoscopy with local or general anesthesia.

Bronchoalveolar lavage (BAL) is a diagnostic technique through which information is obtained about conditions in peripheral parts of the bronchoalveolar tree. To determine the impact of general anesthesia on BAL fluid composition, nine patients underwent BAL while under general anesthesia and 16 healthy controls had BAL with local anesthesia. The percentage of recovered fluid and total cell counts were significantly lower in patients under general anesthesia than in controls. The number of viable cells, the proportions of the various cells, and the BAL albumin-serum albumin ratio did not differ between the groups. Thus, general anesthesia with controlled ventilation, as performed in this study, apparently does not seriously after the prerequisites for BAL.

Adult↗

Human herpesvirus-6 (HHV-6, HBLV) in sarcoidosis and lymphoproliferative disorders.

Serologic studies were done to estimate the antibody prevalence against human herpesvirus 6 (HHV-6) in patients with malignant lymphomas, Sjögren's syndrome and sarcoidosis. Serologic studies showed IgG antibody titers against HHV-6 in up to 41% of patients with sarcoidosis, 50-70% with malignant lymphomas and in 36% with Sjögren's syndrome. In situ hybridization on lymph node biopsies was positive for HHV-6 genome in 1 out of 5 sarcoidosis lymph nodes.

Antibodies, Viral↗

Translocation t(13;14) in nine generations with a case of translocation homozygosity.

The Robertsonian translocation 5(13;14)(p11;q11) was studied in three families with probable common ancestry in Eastern Finland. In the largest family the translocation has segregated through at least nine generations. The same family also included a female who was homozygous for t(13;14). No clear-cut effect of the translocation on fertility could be demonstrated and only one case of trisomy 13 was recorded in the offspring of t(13;14) carriers. The results are discussed, with implication for human chromosomal evolution.

Abortion, Spontaneous↗

Anaesthetic properties of pregnanolone in mice in an emulsion preparation for intravenous administration: a comparison with thiopentone.

The anaesthetic properties of pregnanolone emulsion, which is a new pharmaceutically and clinically acceptable preparation of pregnanolone, have been evaluated and compared with those of thiopentone in the mouse. "Loss of the righting reflex" for 15 sec. was used as a criterion for the anaesthetic effect. The range for the optimal infusion rate to reach the threshold anaesthetic dose was 0.25-1.0 mg/kg/min. for pregnanolone and 10-40 mg/kg/min. for thiopentone. Potency, measured at the optimal infusion rate as the mean anaesthetic dose, AD50, or as the threshold anaesthetic dose, was about six times higher for pregnanolone than for thiopentone. The induction of anaesthesia, which ensured directly after a complete dose was given, and the duration of anaesthesia were similar for pregnanolone and thiopentone in equipotent doses. The approximate therapeutic index for pregnanolone was about four times higher than that for thiopentone. The range for the time of anaesthesia was about 150 min. for pregnanolone emulsion but only about 50 min. for thiopentone. Recovery of the mice from anaesthesia occurred within minutes after pregnanolone, whereas it took hours following thiopentone. In conclusion, these results show that the advantage of pregnanolone emulsion over thiopentone include a higher therapeutic index, a wider range for the duration of anaesthesia and a shorter recovery period.

Anesthetics↗

Exposure to microorganisms, airway inflammatory changes and immune reactions in asymptomatic dairy farmers. Bronchoalveolar lavage evidence of macrophage activation and permeability changes in the airways.

Lung function, bronchial reactivity, serum antibody levels, bronchoalveolar lavage (BAL) fluid and the magnitude of exposure to airborne microorganisms during farm work were studied in 10 healthy farmers with no respiratory symptoms. Lung function and bronchial reactivity were not altered. An increase in the amount of antibodies against several microorganisms could be demonstrated but precipitating antibodies were observed only in two subjects. In the BAL fluid the nonsmoking farmers had elevated proportion of lymphocytes and elevated levels of albumin, fibronectin and angiotensin-converting enzyme while the levels of hyaluronan and procollagen III N-terminal peptide were within normal limits. The lung function, bronchial reactivity, serum antibody levels and BAL findings were not correlated with the exposure to airborne microorganisms. We conclude that healthy farmers, exposed to mold dust, may exhibit signs of alveolitis including albumin leakage, accumulation of inflammatory cells and alveolar macrophage activation.

Adult↗

Relationship between serum neopterin and lymphocytic alveolitis in sarcoidosis.

We have previously found elevated levels of serum (S-) neopterin in patients with active sarcoidosis. In the present study we therefore investigated the relationship between elevated S-neopterin and sarcoid alveolitis as reflected in bronchoalveolar (BAL) findings. Patients with elevated percentages of BAL-lymphocytes (n = 19) had significantly higher (p less than 0.01) S-neopterin levels (median 12.1 nmol/L) than those (n = 11) with normal percentages (median 8.5 nmol/L). Of 19 patients with elevated lymphocyte percentage 18 had increased S-neopterin. There was a significant correlation between S-neopterin levels and the concentration (p less than 0.01) as well as the percentage (p less than 0.05) of BAL-lymphocytes. On the other hand, no correlation was found between S-neopterin and the BAL-albumin/S-albumin ratios, the concentration of macrophages or the concentration of angiotensin converting enzyme in the BAL fluid. The results indicate a close relationship between S-neopterin and lymphocytic alveolitis in sarcoidosis. Furthermore, a possible relationship between elevated S-neopterin and the ratios of T helper to T cytotoxic-suppressor cells (TH/TC-S) in blood, assumed to reflect changes of the ratios in alveolitis, was examined. However, 34 of 37 sarcoid patients had TH/TC-S ratios within the normal range. The ratios of patients with normal and elevated S-neopterin did not differ.

Adult↗

Effects of oral N-acetylcysteine on cell content and macrophage function in bronchoalveolar lavage from healthy smokers.

Bronchoalveolar lavage (BAL) was performed in fourteen healthy non-smokers and eleven healthy smokers. In smokers BAL was performed before and after eight weeks' treatment with N-acetylcysteine (NAC; 200 mg t.i.d.). Cell number, composition and viability were determined in the BAL fluid. Alveolar macrophages (AMs) were cultured before examination of their phagocytic capacity and their ability to produce leukotriene B4 (LTB4). BAL fluid from smokers contained more cells than that from non-smokers (p less than 0.001). This was mainly attributable to increases in both proportion and absolute number of AMs (p less than 0.001) and to an increase in absolute number of neutrophils (p less than 0.05). However, there was a decrease in proportion of lymphocytes in BAL fluid from smokers (p less than 0.001). Phagocytic capacity of adherent cells and capacity of AMs to generate LTB4 after stimulation with opsonized zymosan (OZy) were decreased in smokers (p less than 0.05 and p less than 0.01 respectively). NAC treatment of smokers did not affect cell number but resulted in an increased proportion of lymphocytes in BAL fluid (p less than 0.05). The phagocytic capacity of AMs was not significantly altered but was improved in five of eleven smokers after NAC treatment. NAC also enhanced the decreased LTB4 secretion by smokers' AMs (p less than 0.05). We conclude that smoking leads to reduced phagocytic capacity and LTB4 secretion of AMs and that oral NAC treatment may improve the function of AMs.

Acetylcysteine↗

Oral N-acetylcysteine reduces selected humoral markers of inflammatory cell activity in BAL fluid from healthy smokers: correlation to effects on cellular variables.

Bronchoalveolar lavage (BAL) was performed on eleven healthy smokers before and after eight weeks of oral treatment with N-acetylcysteine (NAC) 200 mg t.i.d. The concentrations of selected eosinophil and neutrophil granule constituents and of selected proteases and protease inhibitors, albumin and endotoxin were determined in the recovered BAL fluid and in plasma or serum samples. In addition, in vitro chemotactic activities for neutrophils and eosinophils were assessed in the BAL fluid. Significant reductions in BAL fluid content of lactoferrin (LF), eosinophil cationic protein (ECP), antichymotrypsin (ACT) and chemotactic activity for neutrophils were recorded after NAC treatment. The levels of other examined markers tended to be reduced or were not affected. In serum/plasma, the concentrations of myeloperoxidase (MPO) and elastase were reduced after NAC treatment whereas concentrations of other constituents examined were unaltered. These data, together with previously reported findings, suggest that oral NAC may influence the activity of "inflammatory" cells in the bronchoalveolar space of smokers.

Acetylcysteine↗

Subcellular localization of angiotensin-converting enzyme in the human alveolar macrophage.

The present investigation was performed in order to elucidate the subcellular localization of angiotensin-converting enzyme (ACE) in human alveolar macrophages. A pure population of alveolar macrophages was obtained by centrifugal elutriation of bronchoalveolar lavage (BAL) fluid from seven sarcoid patients. The cells were homogenized by sonication and the postnuclear supernatant was fractionated on a discontinuous sucrose gradient. Fractions of particulate material were collected and characterized by marker enzymes. The distribution pattern of ACE closely resembled that of NADPH-cytochrome-c-reductase and sialyltransferase, markers of the endoplasmic reticulum and the Golgi complex, respectively, indicating a common localization. This localization is compatible with synthesis taking place in the alveolar macrophage.

Adult↗

Hyaluronic acid in bronchoalveolar lavage in rats exposed to quartz.

Hyaluronic acid, a connective tissue component, in bronchoalveolar lavage fluid (BAL) is correlated with decreased lung volumes in sarcoidosis. To investigate whether hyaluronic acid could be a marker of fibrosis in another interstitial lung disease, silicosis, the level of the substance in BAL fluid from rats exposed to crystalline silica (n = 3), amorphous silica (n = 3), and in one sham injected rat was measured. There was an increase in the total number of alveolar cells recovered in the rats exposed to crystalline silica and also a pronounced increase in the proportions of neutrophils and lymphocytes. In addition, the concentration of hyaluronic acid was high in this group of rats, and electron microscopic investigation of the lungs showed fibrosis. Thus hyaluronate in BAL fluid in rats exposed to crystalline silica seems to be a possible marker of fibrotic changes.

Animals↗

Hyaluronate in bronchoalveolar lavage fluid in sarcoidosis and its relationship to alveolar cell populations.

Hyaluronate is a potential marker of activated pulmonary fibroblasts and appears in increased amounts in bronchoalveolar lavage fluid from patients with sarcoidosis. This study was performed to investigate a possible link between the local immune response and pulmonary fibroblast proliferation. The median hyaluronate concentration in the lavage fluid from 23 sarcoid patients was 12.0 (interquartile range 7.5-28.5) micrograms/l. The hyaluronate concentration was positively correlated to the concentration and proportion of lymphocytes (p less than 0.001 and p less than 0.01, respectively) as well as to the concentrations of T lymphocyte subsets (OKT4+ p less than 0.01, OKT8+ p less than 0.05). No correlation was found between the hyaluronate concentration and the OKT4+/OKT8+ ratio. Furthermore, a significant correlation was observed in the lavage fluid between hyaluronate and angiotensin-converting enzyme, a marker of monocyte/macrophage activity (p less than 0.01). Thus, the intensity of the sarcoid alveolitis was associated with biochemical signs of pulmonary fibroblast proliferation/activation in sarcoidosis.

Adult↗

Human alveolar macrophages from smokers have an impaired capacity to secrete LTB4 but not other chemotactic factors.

The function of alveolar macrophages (AM phi s) was studied in terms of the secretion of various chemotactic factors. Human AM phi s were obtained by BAL from healthy non-smokers and smokers. One of the chemotactic factors was LTB4, an arachidonic acid metabolite of the lipoxygenase pathway. The amount of LTB4 was determined in culture medium, in cell homogenate and in BAL-fluid. The total chemotactic activity for neutrophils was measured in culture medium and in BAL-fluid. AM phi s from smokers showed an impaired secretion of LTB4. The spontaneous secretion in vitro was inhibited by 90% (p less than 0.05) and the stimulated one was blocked by 84% (p less than 0.05). This impairment was not followed by a decrease in total chemotactic activity, indicating the existence of other chemotactic factors than LTB4. Preliminary characterization of the chemotactic activity by gel filtration demonstrated at least four different chemotactic factors. Budesonide inhibited both the release of LTB4 and the total chemotactic activity in medium from stimulated AM phi s.

Bronchoalveolar Lavage Fluid↗

Tuberculostearic acid in lymph nodes from patients with sarcoidosis.

It has earlier been suggested that mycobacteria may play an aetiological role in the development of sarcoidosis. To investigate this further we analyzed the presence of a characteristic mycobacterial constituent, tuberculostearic acid (TS, 10-methyloctadecanoic acid), in lymph nodes from 22 patients with sarcoidosis and in eleven children and three adult controls. To detect TS gas chromatography/mass spectrometry was used. These findings were compared with the results from conventional mycobacterial culture and radiometric respirometry. Although the latter techniques failed to detect mycobacteria in all the tested tissue samples, TS was found in various amounts. Thus, 0-3 micrograms TS/g freeze-dried tissue was noted in eight sarcoid patients, 3-50 micrograms TS/g in eight and 51-400 micrograms TS/g in the remaining six patients. Among the controls only 1/14 had detectable TS. In one patient with lymph node tuberculosis TS was in the range 51-400 micrograms/g. We conclude that the findings could be explained by the presence of mycobacteria not cultivable with the studied techniques or with the presence of remnants after an earlier colonisation with mycobacteria, e.g. BCG-vaccination. Mycobacteria or mycobacterial cell-envelope in sarcoid tissue may possibly act as cofactors in the development of the disease, i.e. they might function as triggering agents (adjuvans) of the immune response. On the other hand the findings may be without any aetiological significance. In that latter case a hitherto unknown lack of wax decomposition during several decades has to be considered.

Adult↗

No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid.

Six healthy volunteers underwent bronchoalveolar lavage (BAL) before and after receiving N-acetylcysteine (NAC) 600 mg daily for 2 weeks. Free and total NAC, cysteine and glutathione were determined in the lavage fluid, lavage cells and plasma. No NAC was demonstrated, free or bound in disulfides, in either of the lavage components; furthermore, the cysteine and glutathione content of these components and their respective redox states were unaltered during therapy. Plasma free and total cysteine content was unaltered by administration of the drug, but both free and total plasma glutathione increased significantly. Free NAC could not be detected in plasma following dosing. However, a mean of 0.3 nmol/100 microliters plasma was released from disulfides in plasma following reduction with dithiothreitol. N-acetylcysteine has been proposed to act as a mucolytic by cleavage of disulfide bonds. Our findings do not support this direct mode of action and alternative mechanisms of action must be sought.

Acetylcysteine↗

Effect of dietary proteins on hepatic and plasma lipids, and some properties of major plasma lipoprotein fractions during dietary-induced hypercholesterolemia in male rats.

In order to characterize further the cholesterolemic effect of casein compared with soybean protein isolate, each of these proteins were fed to male rats at different levels of dietary cholesterol administration. An increase in the dietary cholesterol level from zero to 0.25% led to a several-fold increase in plasma triacylglycerols with a comparatively small rise in plasma cholesterol. Further increase in the cholesterol content of diet to 0.5, 1 and 2% resulted in a return of plasma triacylglycerols to normal or even subnormal values, whereas the plasma cholesterol values rose progressively. The triacylglycerolemic and cholesterolemic effects were 2-3-fold higher with casein diet than with soybean protein diet, respectively. A major part of the increased plasma cholesterol value was accounted for by cholesterol in the very-low-density lipoprotein (VLDL) fraction. Even at moderate levels (0.05-0.5%), the dietary cholesterol administration produced a series of changes in the electrophoretic pattern of plasma lipoproteins. These changes were more prominent in the rats fed casein diet, which often showed an enhanced VLDL band even on a cholesterol-free diet. An additional lipoprotein band, localized between VLDL and the LDL/HDL1 band, was observed in several rats fed casein diet with 0.05 or 0.1% cholesterol, and in rats fed soybean protein diet containing 0.25 or 0.5% cholesterol. In contrast, at the 0.25 and 0.5% levels of dietary cholesterol, plasma of casein-fed rats contained only one broad band within the VLDL-LDL/HDL1 region. All these findings indicate that casein diet promotes the appearance of one or more specific type(s) of cholesterol-induced plasma lipoprotein particles even at a comparatively low level of dietary cholesterol.

Animals↗

Improved banding pattern of rat plasma lipoproteins developed by agarose gel electrophoresis at pH 7.0.

The use of a conventional agarose gel electrophoretic method to separate rat plasma lipoproteins resulted in a rather poor resolution of lipoproteins of lower density. Therefore, attempts were made to improve the resolution by running the electrophoresis under different conditions. It was shown that rat plasma lipoproteins could be separated into at least three fractions by agarose gel electrophoresis in phosphate buffer at pH 7.0. Using rat plasma lipoproteins isolated by sequential flotation as standards, these fractions were shown to correspond to high-density lipoprotein (HDL2), very-low-density lipoprotein (VLDL) and a mixed low-density lipoprotein (LDL)/high-density lipoprotein (HDL1) fraction. Since VLDL is completely separated from the other lipoprotein classes the method could be used to monitor changes in plasma VLDL.

Animals↗