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Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 163 records · Page 9Linked to original sources

Extracellular matrix components in bronchoalveolar lavage fluid in sarcoidosis and their relationship to signs of alveolitis.

In lung sarcoidosis, the mutual relationships of three components of the extracellular matrix, fibronectin (FN), hyaluronan (HA), and type III procollagen peptide (PCP), were investigated in the bronchoalveolar lavage (BAL) fluid. Furthermore, their relation to signs of alveolitis and of fibrosis was examined. Sarcoidosis patients (n = 74) had significantly (p less than 0.001) increased BAL fluid concentrations of FN, HA, and PCP, as well as albumin and lymphocytes, compared to controls (n = 57). The increases were significantly higher in clinically active than in inactive sarcoidosis. FN, HA, and PCP were significantly correlated to markers of alveolitis, such as albumin (r approximately 0.6-0.7; p less than 0.001) and lymphocytes (r approximately 0.4-0.5; p less than 0.001 for FN and HA; p less than 0.05 for PCP), indicating that an alveolar inflammatory process may be a prerequisite for the increased production of the three components. Since correlations between FN and HA and functional parameters (VC, TLC, FEV1.0, and DLCO) were low (r approximately 0.2-0.3, p less than 0.05-0.01 for FN and HA), the increased levels of the extracellular markers do not seem to reflect developed fibrosis. The three markers of extracellular matrix showed significant (p less than 0.001) mutual correlations in the sarcoid patients (r approximately 0.7). FN and HA were correlated even in controls (r = 0.5; p less than 0.01). The findings are in agreement with our hypothesis that these compounds may participate in the buildup of an extracellular network that supports the healing process but in excess may eventually lead to fibrosis.

Adult↗

Determination of fibronectin and its degradation products in bronchoalveolar lavage fluid.

In order to estimate, in sarcoidosis, the extent of degradation and the availability of functionally active fibronectin (FN) in the alveolar space, native and total (= native + degraded) FN were determined in the bronchoalveolar lavage (BAL) fluid of 28 non-smoking patients with sarcoidosis, 12 healthy non-smokers and 24 asymptomatic smokers. The FN was measured in unconcentrated BAL fluid in the presence of the protease inhibitor aprotinin: total FN was assayed by a double-antibody sandwich enzyme-linked immunoadsorbent assay (ELISA) and native FN by a gelatin-antibody sandwich ELISA. Both in controls and in sarcoid patients, concentrations of native FN were lower than those of total FN, indicating that FN is degraded in the alveolar space. Compared to non-smoking controls, the sarcoid patients had significantly increased concentrations of both native and total FN (p less than 0.001 for both) in the BAL fluid. Native FN in percentage of total FN was similar in non-smoking sarcoids and controls, representing about 80% and 70%, respectively. In contrast, native FN corresponded to only 30% in the group of control smokers, indicating higher degradation in smokers. Thus, in smokers, less intact collagen-binding FN is available for forming an extracellular matrix, which may be necessary for repair. On the other hand, the elevation of FN, especially in its native form, in sarcoidosis implies that more of it may be available for repair but, if in excess, also for the build-up of fibrotic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bilateral spontaneous pneumothorax and sarcoidosis.

We report on a 44-year-old smoking man with sarcoidosis stage III presenting with bilateral spontaneous pneumothorax. The diagnosis was confirmed by biopsies from the lung parenchyma, visceral pleura and bronchial mucosa. Bilateral pleurectomy was needed since long-term tube drainage turned out to be unsuccessful.

Adult↗

Metabolism of very low density lipoproteins in rats with isotretinoin (13-cis retinoic acid)-induced hyperlipidemia.

A significant rise in plasma triacylglycerols from the control level of 0.89 mmol/l to 1.88 mmol/l (P less than 0.001) was observed in male Sprague-Dawley rats treated for 11 days with isotretinoin (oral dosing; 10 mg/day). This rise was due to an increased level of plasma very low density lipoproteins (VLDL). When VLDL from untreated rats were labeled with 125I-labeled tyramine-cellobiose and injected intravenously into rats treated for 10 days with isotretinoin (n = 6) and in control rats (n = 6), it was found that the disappearance of radioactivity from the blood was dramatically retarded in the treated animals. The disappearance could be divided into two phases, a rapid (alpha) phase dominated the first 5 min and was followed by a slower (beta) phase. The half-life of the beta-phase increased significantly from 53 +/- 7 min in the controls, to 120 +/- 62 min after isotretinoin. VLDL prepared from isotretinoin-treated animals (n = 6) had about the same half-life in control animals (62 +/- 8 min) as had ordinary VLDL. The elimination of tracer from the blood was mainly due to uptake by the liver. The amount of radioactivity in the liver after 30 min of circulation was significantly reduced from 34 +/- 7% of injected dose in controls to 24 +/- 5% in the isotretinoin group (P = 0.013). The uptake in other organs was less than 3% per organ and was essentially unaffected by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sarcoidosis with pleural involvement mimicking a coin lesion.

We present the case of a 37 year old non-smoking man with a tumour like infiltration of the left lung caused by sarcoidosis with pleural involvement not detectable at chest X-ray. The diagnosis was made at thoracotomy and confirmed by a Kveim test.

Adult↗

99mTc-DTPA clearance measured by a dual head gamma camera in healthy subjects and patients with sarcoidosis. Studies of reproducibility and relation to bronchoalveolar lavage findings.

99mTc-DTPA clearance was studied in ten healthy non smokers, five asymptomatic smokers and nine non smoking patients with sarcoidosis in the supine position with a dual head gamma camera allowing simultaneous information of regional clearance rates in frontal and dorsal projections. In the patients with sarcoidosis, a bronchoalveolar lavage was performed prior to the clearance study. DTPA clearance rate was measured during 60-90 min and data were corrected for recirculating radioactivity. The coefficients of variation for measurements on 2 consecutive days in the 10 healthy non smokers were 9%-11% for the right and left lung, anterior and posterior projections. The T1/2 calculated from total lung projections were 90-92 min for the anterior view and 84-85 min for the posterior view. Regional measurements did not add further information. No apico-basal difference was found but there was a significant fronto-dorsal gradient in 99mTc-DTPA clearance in the supine position. Smokers had significantly (P less than 0.01) faster clearance rates (T1/2 28 +/- 10 min) than healthy controls. In the sarcoidosis group clearance rates were increased in four patients and no relationships were found between DTPA clearance rates and inflammatory markers (lymphocytes, albumin, ACE) in the bronchoalveolar lavage fluid.

Adult↗

Determination of HDL2 cholesterol by precipitation with dextran sulfate and magnesium chloride: establishing optimal conditions for rat plasma.

Optimal conditions for analyzing HDL2 cholesterol in small amounts of rat plasma have been studied using different concentrations of dextran sulfate and MgCl2 to precipitate lipoproteins containing apolipoprotein B and/or apo E. When the MgCl2 level was 91 mM, the supernate cholesterol was rather constant at a level of about 50-60% of the total plasma cholesterol concentration. Immunochemical determination of the apo A-I content indicated that no major losses of the HDL2 fraction took place under these conditions. The recovery of about 96% of HDL2 lipoproteins after the precipitation of rat plasma and the almost complete absence of lipoproteins belonging to the VLDL, LDL and HDL1 fractions was demonstrated by agarose gel electrophoresis. Thus, the method should be suitable for screening the HDL2 cholesterol content in small volumes of rat plasma.

Animals↗

Effect of metoprolol on plasma lipids and arterial intimal lipid deposition in spontaneously hypertensive rats.

The purpose of the present study was to characterize possible effects of dietary-induced plasma lipid elevations on the development of arterial lesions in spontaneously hypertensive rats (SHR) and to reveal any influence of treatment with metoprolol on these parameters. Metoprolol treatment caused an 8% decrease in heart rate and a 13% decrease in blood pressure and led to a rise in plasma triglycerides, 24%, 17% and 34% after 1, 3 and 6 months of metoprolol treatment, respectively. However, no effect on plasma triglycerides was observed after 9 months of metoprolol treatment while a reduced cholesterolemic response was observed. Intimal proliferations containing accumulations of lipids were observed in small intramural branches of coronary arteries (greater than 100 microns) in 11 of 31 control rats fed the atherogenic diet for 9 months. In contrast, similar changes were observed in only 1 of 34 metoprolol-treated rats fed an otherwise identical diet. The corresponding figures for the frequency of lipid containing intimal plaques in aorta were 6/19 in controls and 2/24 in the metoprolol-treated group.

Animals↗

Characteristics of alveolar cells and soluble components in bronchoalveolar lavage fluid from non-smoking aluminium potroom workers.

Aluminium potroom workers have been reported to develop severe pneumoconiosis and bronchial hyperreactivity. The influence of inhalation of aluminium oxide and fluorides on the alveolar milieu was studied by bronchoalveolar lavage (BAL) in 14 male non-smoking potroom workers; 28 non-smoking healthy volunteers served as controls. The total numbers, concentrations, and proportions of various alveolar cells did not differ between the groups. The concentrations of albumin and fibronectin in BAL fluid were significantly higher (p less than 0.01 for both) in the exposed workers, reflecting an increased alveolar capillary permeability and an activation of alveolar macrophages (AMs). The concentration of angiotensin converting enzyme, another AM marker, was, however, decreased (p less than 0.01) in the workers. The concentration of hyaluronan, a fibroblast marker, did not differ between the groups. AMs from workers had a decreased capacity (p less than 0.05) to interact with yeast C3b particles but not to ingest them. The expression of HLA-DR and OKM1 on the cell surfaces of AMs were equal in the two groups. The BAL findings were not accompanied by restrictive lung disease in the workers. The fact that only a discrete alveolitis was found in the potroom workers may be due to a low grade of exposure to alumina and fluorides and to frequent use of respiratory protection equipment.

Adult↗

Effects of diet and metoprolol on lipid levels in the blood plasma and morphology of the heart and intramural branches of coronary arteries of spontaneously hypertensive male rats. A 9-month study.

Semipurified diets containing 0.5% cholesterol were used in a 9-month study with spontaneously hypertensive male rats to characterize the effects of the protein source (casein vs. soybean protein), and the selective beta 1-adrenoceptor antagonist metoprolol on both lipid levels in blood plasma and the aorta, and on the morphology of intramural branches of coronary arteries. Raised blood lipid levels were observed in these rats. A significant decline in HDL2 cholesterol took place, while plasma cholesterol belonging to lipoprotein fractions of lower density increased. Metoprolol treatment led to a substantial elevation of the plasma triacylglycerol level and, with time, a reduced cholesterolemic response. The use of soybean protein instead of casein had a persistent plasma lipid-lowering effect. Arteriosclerotic changes in the form of musculo-elastic thickenings, intimal cushions and homogeneous hyalin deposits appeared in the intramural coronary arteries of rats in all groups after 9 months on the diet. However, intimal deposition of lipid was only present in rats belonging to the casein group not treated with metoprolol. Rats of this group also showed more severe myocardial lesions in the form of scar tissue with or without inflammatory cell reaction.

Animals↗

Autofluorescence in human alveolar macrophages from smokers: relation to cell surface markers and phagocytosis.

Flow cytometry was used to study the influence of smoking histories on autofluorescence, expression of surface markers, and phagocytic ability in alveolar macrophages (AM) recruited by bronchoalveolar lavage (BAL) from healthy smokers (n = 13) and nonsmokers (n = 13). Alveolar macrophages have an autofluorescence that can be quenched by a recently developed technique. In the present study, this technique was used in combination with flow cytofluorometry. Alveolar macrophages from smokers (mean 10.6 +/- 7.6 pack-years) showed a significantly (p less than .001) increased autofluorescence compared to nonsmokers. This autofluorescence was associated with an increased complexity of the cells but not with altered cell volumes. No correlation was seen between the mean fluorescence intensity and the cigarette consumption among smokers. Despite the difference in autofluorescence, no altered expression of surface markers known as markers of cell activation (HLA-DR, CR3) was detected in AMs from smokers compared to nonsmokers. The functional ability of AMs to ingest C3b-coated particles analyzed with a fluorescence quenching assay did not differ between the groups. The lack of correlation between the cigarette consumption and the autofluorescence suggests a maximal fluorescence intensity in the present population of smokers. The biological mechanism behind this autofluorescence needs to be further investigated.

Adult↗

Lung function and bronchial reactivity in aluminum potroom workers.

Lung function and bronchial reactivity were measured in 38 aluminum potroom workers with no airway symptoms and in 20 healthy referents (office workers). All of the participants were non-smokers. The magnitude of exposure to airborne dust (alumina) and fluorides was determined. The aluminum potroom workers had obstructive lung function impairment with a significant decrease in expiratory flow and an increase in residual volume. Diffusing capacity was found to be lower than in the referents. No bronchial hyperreactivity was found in the aluminum potroom workers. The exposure to inhaled alumina and particulate and gaseous fluorides in the plant was low, 15-20% of the Swedish exposure limits. The finding of only modest lung function alterations with no bronchial hyperreactivity in the aluminum potroom workers is not consistent with the results of other authors. This discrepancy can probably be explained by the fact that the exposure to inhaled contaminants in the investigated aluminum plant was low.

Adult↗

V/Q and alveolar gas exchange in pulmonary sarcoidosis.

Eleven patients with pulmonary sarcoidosis of type II or III were investigated with regard to regional distribution of ventilation and perfusion (V/Q), alveolar gas exchange and diffusion limit at rest and during exercise. Lung volumes were 50-65% of normal values. Flow-volume curves indicated obstructive changes. The transfer factor was 75% (range 16-120%) of predicted. Perfusion scintigraphy showed marked defects in 7 out of 11 patients. Radiospirometry showed matching ventilation and perfusion defects and washout of xenon was prolonged. There was a venous admixture at rest of 9%. Arterial oxygen tension (Pao2) averaged 9.7 kPa. V/Q analyses indicated the presence of a small shunt (1%), regions with low V/Q in 4 out of 11 patients, regions with high V/Q in 5 out of 11 patients and increased wasted ventilation. At rest measured Pao2 was lower (0.6 kPa) than predicted from the V/Q distribution. During mild supine exercise causing significant dyspnoea, pulmonary vascular resistance rose to abnormal values, 5.2 mmHg.l.-1 min-1.m2 BSA. The venous admixture decreased to 5.4%. The shunt was unchanged, as was the perfusion of regions with low V/Q. The regions with abnormally high V/Q disappeared. Measured Pao2 decreased to 9.1 kPa, while calculated Pao2 remained unchanged. Thus the P(A-a)o2 at rest (4.2 kPa) was 70% caused by shunt and V/Q mismatch. During exercise alveolar-arterial pressure difference for oxygen measured P(A-a)o2 rose further to 5.1 kPa, while calculated P(A-a)o2 remained unchanged and was only 50% caused by shunt and V/Q disturbances. The difference between calculated and measured Pao2 indicated significant diffusion limitation both at rest and during mild exercise.

Adult↗

Exudative pericarditis in sarcoidosis. A case report and echocardiographic study.

Involvement of the pericardium in sarcoidosis is infrequent as earlier reported. The involvement may be accompanied by pericardial effusion. We report the case of a 43 year-old man with non-obstructive hypertrophic cardiomyopathy for almost two decades who developed an effusion in the pericardial sac. As pericardial effusion is not a part of this disease and no other common cause was found we believe that the exudation was caused by sarcoidosis which started one year earlier. This finding initiated an echocardiographic study in 18 consecutive sarcoid patients, 8 with acute and 10 with chronic disease. None had pericardial effusion and only one demonstrated a thickening of the pericardial tissue.

Adult↗

Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms.

The human and bovine forms of the hydrophobic 3.7 kDa surfactant polypeptide have been structurally analyzed. The polypeptide is essentially inert to enzymatic proteolysis, and methods for analysis include peptide handling in organic solvents and fragment generation by limited acid hydrolysis. The molecule exhibits N-terminal trimming, and the relative abundance of the different starting positions varies both among species and between adult and fetal forms of the surfactant polypeptide. The bovine major form is one residue shorter than the mature 35-residue human molecule. Comparison of the porcine, human and bovine polypeptides reveals a conserved hydrophobic middle/C-terminal segment and a variable hydrophilic N-terminal part.

Amino Acid Sequence↗