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Biomedical subjects

O Andersson

Publications and source records attributed to O Andersson.

At least 55 records · Page 3Linked to original sources

Bronchial exudation of bulk plasma at allergen challenge in allergic asthma.

This study examined plasma exudation into the bronchial lumen after allergen challenge. A novel low-trauma technique was developed to challenge and lavage a medium-sized lingular or middle lobe bronchus. Eleven subjects with challenge-assessed pollen-sensitive asthma were allocated to fiberbronchoscopy in the supine position. In the control bronchus 0.5 ml diluent was instilled. The bronchus was occluded proximally 3 min later by inflation of a balloon, and lavage was carried out twice with 25 ml saline. Incremental doses of allergen solution (0.5 ml) were then instilled in the contralateral lung. The challenge continued until a clearly visible bronchial reaction occurred and was immediately followed by the same lavage as on the control side. The lavage liquids were analyzed for the presence of plasma exudation and mast cell activation indices. On the allergen-challenged side, tryptase, reflecting mast cell activation, was increased by 150% (p < 0.01) compared with the control side. Fibrinogen (mol wt 340,000), reflecting large protein exudation, was increased by 840% (p < 0.05), and N-alpha-tosyl-L-arginine-methyl esterase activity, reflecting both large protein exudation and mast cell activation, increased by 480% (p < 0.01). The level of albumin (mol wt 69,000), the major luminal protein under baseline conditions, increased but not significantly. We conclude that activation of mast cells and luminal entry of little sieved plasma exudates occur early after endobronchial allergen provocation in human subjects with allergic asthma.

Albumins↗

The interconnection between sympathetics, microcirculation, and insulin resistance in hypertension.

The pathophysiology of the frequent association of insulin resistance and hypertension has not been elucidated. The skeletal muscle is the major site of insulin resistance; when stimulated with insulin, the hypertensive skeletal muscles extract less glucose than the normotensive. We postulate that hypertension-related changes in the skeletal muscle microcirculation contribute to the impaired glucose uptake in hypertension. Vascular rarefaction in hypertension impairs the delivery of insulin and glucose to muscle cells. Insulin resistance has been described both in human and experimental hypertension and both conditions are associated with vascular rarefaction. Functional studies (response to whole body or forearm exercise) and anatomic investigations (conjunctival photography, mesenteric and muscle biopsies) show vascular rarefaction in human hypertension. In addition, patients with hypertension are known to have a larger proportion of insulin resistant, poorly vascularized fast twitch muscle fibers. A few interventions can increase or decrease insulin resistance and these effects can be explained on hemodynamic grounds. Beta adrenergic blocking agents aggravate insulin resistance, and their main hemodynamic effect is a decrease of cardiac output. Converting enzyme inhibitors, alpha adrenergic blocking agents and possibly calcium antagonists decrease the insulin resistance, and their major hemodynamic effect is vasodilation. Physical training decreases insulin resistance; a higher capillary density in skeletal muscles is the hallmark of physical training. A hypothesis ought to rest on sufficient supporting data and its validity ought to lend itself to experimental verification. We believe our hypothesis meets both criteria. After outlining the supporting evidence we propose a number of tests to prove or disprove the hypothesis. In addition to the testable hypothesis we also speculate on the possible cause of the frequent association between hypertension and insulin resistance. We propose that both insulin resistance and blood pressure elevation represent a facet of the "defense reaction" which might have offered an early survival advantage and may, over evolutionary times, have fostered natural selection of subjects with both conditions.

Animals↗

Purification and level of expression in bronchoalveolar lavage of a human polychlorinated biphenyl (PCB)-binding protein: evidence for a structural and functional kinship to the multihormonally regulated protein uteroglobin.

A human lung polychlorinated biphenyl (PCB)-binding protein was purified by sequential chromatography of lavage fluid incubated with the tritium-labeled, high-affinity ligand, 4,4'-bis(methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl. From sodium dodecyl sulfate polyacrylamide gel electrophoresis gradient gels, it was evident that a single band with an approximate molecular weight of 13 kD was present in the eluate from the final chromatographic step. Antibodies raised against the human lung PCB-binding protein detected a single band of corresponding size in lavage fluid in immunoblotting experiments. Furthermore, the antibodies detected significantly higher levels of the lung PCB-binding protein in lavage fluid from nonsmokers as compared to smokers. The purified protein was sequenced, and an alignment of the obtained aminoterminal amino acid residues of the human lung PCB-binding protein to uteroglobin and to a rat lung PCB-binding protein revealed an overall positional identity of approximately 45%. The amino acids suggested to participate in ligand binding of uteroglobin were extensively conserved in the PCB-binding proteins. Thus, we conclude that we have purified and raised antibodies against a human lung PCB-binding protein and that it has a structural as well as a functional kinship to the steroid-binding and multihormonally regulated rabbit protein uteroglobin.

Amino Acid Sequence↗

Glucocorticoid receptor mRNA expression in pulmonary alveolar macrophages in sarcoidosis.

The presence of the glucocorticoid receptor was demonstrated by immunocytochemistry in pulmonary alveolar macrophages obtained by bronchoalveolar lavage. Also, GR mRNA content was determined by solution hybridization in PAM from 12 healthy volunteers and in 6 patients with sarcoidosis. No significant differences with regard to GR mRNA expression was detected between the two groups examined. For comparison, lung tissue from three patients undergoing thoracic surgery was examined and found to contain GR mRNA levels in the same range. As an indication of GR function, we also determined the mRNA levels of a glucocorticoid-regulated gene, metallothionein IIA, during basal conditions and after in vitro incubation of PAM with dexamethasone. Neither the control sample nor the dexamethasone-stimulated MTII mRNA values in PAMs differed significantly between the two groups. Solution hybridization is a rapid, sensitive and convenient assay which enables accurate and specific quantitation of GR mRNA in PAM. The GR mRNA content and basal as well as dexamethasone-induced MTII mRNA levels in PAM from patients with sarcoidosis is not significantly different from those in healthy volunteers.

Adult↗

Cloning, structure, and expression of a rat binding protein for polychlorinated biphenyls. Homology to the hormonally regulated progesterone-binding protein uteroglobin.

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. Here, we report the isolation of a cDNA encoding the rat lung PCB-binding protein. The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein. Also a monospecific antiserum to the PCB-binding protein recognizes a 13-kDa protein in the homogenates of transfected cells but not in the corresponding fraction of mock-transfected cells. Northern blot analysis of total RNA from different rat tissues demonstrates that the cDNA detects a approximately 600-base pair mRNA which appears to be solely expressed in lung. Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung. Furthermore, amino acids shown by x-ray crystallography to delineate the central cavity of uteroglobin, which fits progesterone, are highly conserved in the two proteins.

Amino Acid Sequence↗

Influences of maternal smoking and fetal sex on maternal serum oestriol, prolactin, hCG, and hPI levels.

A total of 222 pregnant women had repeated hormone assays between 20 weeks and delivery; 86 of the women were smokers. The maternal hormone balance appeared to be affected by smoking. Smoking affected maternal serum levels of hPL and hCG in pregnancies with a female fetus whereas maternal serum concentrations of oestriol and prolactin were affected in pregnancies with a male fetus. Significantly higher hCG levels were found in mothers who smoked and had a girl than in those who smoked and had a boy. On the basis of our results we feel that smoking mainly affects the placenta.

Adult↗

Composition and surface properties of the bronchial lipids in adult patients with cystic fibrosis.

Bronchial secretions from seven patients with cystic fibrosis (CF) were aspirated by fibreoptic bronchoscopy and analysed for lipid composition. The total lipid fraction was also used to measure dynamic surface tension. Pooled samples from 'normal' patients, healthy volunteers, patients with chronic bronchitis, and individual samples from two patients with bronchiectasis were used as controls. Increased bronchial inflammation and infection correlated with a decrease of the phospholipid fraction, and an increase of the cholesterol, diglyceride and triglyceride fractions. When individual phospholipids were analysed, patients with clinically severe CF showed a markedly decreased phosphatidylcholine fraction, whereas the phosphatidylinositol fraction was significantly higher in CF patients than in controls (p less than 0.05). Minimum surface tension was higher in CF patients compared to patients with chronic bronchitis (p less than 0.05). This might be related to earlier reported specific changes in the pattern of fatty acids of the CF bronchial phospholipids.

Adult↗

Stimulation of bronchoalveolar lavage (BAL) and blood lymphocytes by Kveim antigen, tuberculin and concanavalin A in sarcoidosis.

BAL and blood mononuclear cells and their reactivity to Kveim antigen, tuberculin and concanavalin A (Con A) were studied in nine patients with different clinical stages of sarcoidosis. After separation by plastic adherence, non-adherent cells (mainly lymphocytes) were admixed with 10% autologous adherent cells (monocytes/macrophages). After 3 and 6 days' culture with Kveim antigen (1, 10, 100 micrograms/ml), PPD tuberculin (2.5 micrograms/ml) and Con A (10, 20, 40 micrograms/ml) stimulation was measured as incorporation of 14C-thymidine into DNA. Except for occasional reactions the study did not show any unitary significant increase in lymphocyte response to the different concentrations of Kveim antigen in either BAL or blood. For Con A there was a weaker response by BAL-mononuclear cells with no difference between 3 and 6 days, compared with blood where there was an early peak. The lymphocyte reaction to PPD was weak with no difference between blood and BAL.

Adult↗

Human calpactin II (lipocortin I) messenger ribonucleic acid is not induced by glucocorticoids.

Studies were carried out to examine the effect of glucocorticoids on human calpactin II (lipocortin I) mRNA expression. A cRNA probe for human calpactin II (hCPII) was used in a solution hybridization assay to study the effect of dexamethasone on hCPII mRNA levels in human skin fibroblasts, peripheral lymphocytes, pulmonary alveolar macrophages, and HeLa S3 cells. As a positive control, human metallothionein II (hMTII) mRNA levels were measured since hMTII is known to be regulated by glucocorticoids and heavy metals, both of which induce transcriptional activity of the gene. Dexamethasone treatment of these human cell types caused a dose-dependent increase in hMTII mRNA levels, whereas no effect on hCPII mRNA levels was observed. These findings were confirmed in time course studies, where 10(-6) M dexamethasone treatment caused a maximal 2- to 5-fold increase in hMTII mRNA levels after 6-8 h of treatment but no increase in hCPII mRNA levels was observed at any time point up to 24 h. A human glucocorticoid sensitive lymphoid cell line, CEM C7, and a glucocorticoid resistant mutant, ICR-27, isolated from CEM C7, were included in order to confirm the requirement of a functional glucocorticoid receptor (GR) in the induction of glucocorticoid-regulated genes. Dexamethasone (10(-6) M) induced hMTII but not hCPII mRNA in CEM C7 cells, whereas neither hMTII nor hCPII mRNA was induced in ICR-27 cells. In conclusion, our data suggest that glucocorticoids do not induce calpactin II (lipocortin I) mRNA in the human cell types studied.

Annexins↗

Mutagenicity studies by co-cultivation of bronchoalveolar cells and blood lymphocytes with V79 Chinese hamster cells.

Human bronchoalveolar cells, consisting of approximately 85% pulmonary alveolar macrophages (PAMs), and peripheral blood lymphocytes isolated from healthy volunteers were investigated for their ability to metabolize 7,8-diol of benzo[a]pyrene (B(a)P). The mutagenicity of reactive metabolites was analyzed by employing a co-cultivation system using V79 Chinese hamster cells for the detection of mutations. The metabolic activity of the human cells was compared to PAMs isolated from rabbits. The number of PAMs obtained by bronchoalveolar lavage of smokers was found to be significantly elevated compared with nonsmokers. However, the mean number of induced mutations of the 7,8-diol mediated by PAMs during co-cultivation did not differ significantly between smokers and nonsmokers. The aryl hydrocarbon hydroxylase (AHH) activity of human lymphocytes has been studied by others, but to the best of our knowledge this is the first demonstration that human blood lymphocytes could be successfully used in a co-cultivation assay for the characterization of xenobiotic metabolism in terms of mutations, as illustrated by the linear increase of induced mutations in the V79 cells. Rabbit PAMs were less efficient in mediating mutations as compared to both smokers' and nonsmokers' PAMs or lymphocytes. This can probably be explained by less efficient bioactivation of 7,8-diol in rabbit PAMs, which is supported by the fact that the rabbit PAMs metabolized B(a)P in a different way as compared to human PAMs as revealed by HPLC analysis of ethyl acetate extractable metabolites of 3H-B(a)P. No qualitative or quantitative difference in the patterns of B(a)P metabolism by PAMs isolated from smokers and nonsmokers could be established. In conclusion, human PAMs were found to be more efficient in terms of cell-mediated mutagenicity than human lymphocytes, which are more efficient than rabbit PAMs. The present results differ from previous reports concerning the xenobiotic metabolizing capacity of these cells assessed by other methods. This illustrates the usefulness of the co-cultivation assay, because it measures not only the bioactivating capacity of isolated mammalian cells, but also their detoxifying capacity, the transfer of mutagens to other cells and the ability of their metabolites to cause mutations.

Animals↗

ANP--a cardiac hormone and a putative central neurotransmitter.

Isolation, purification and determination of the amino acid sequences of biologically active peptides were performed in 1983-84 by several groups. By that time the existence of such a humoral diuretic/natriuretic factor had been proposed for many years. The main, and perhaps the only, circulating form of atrial natriuretic peptide (ANP) is a 28 amino acid peptide structure with a disulphide bridge. This peptide is distributed mainly peripherally in the right and left cardiac atria. Smaller amounts are found in neonatal cardiac ventricles as well as in autonomic ganglia. In the central nervous system, high concentrations are found in hypothalamus, while lower concentrations are found in midbrain and brain stem regions. The amino acid sequence of ANP in the brain may be shorter than the form originating from cardiac atria. A 1 126 amino acid prohormone is present in granulae of atrial myocytes. After atrial distention the circulating 28 amino acid form is cleaved off. The main actions of this hormone include a diuretic/natriuretic effect, relaxation of vascular smooth muscle, and inhibition of basal or stimulated aldosterone secretion from the adrenal cortex. In the central nervous system, ANP has antidipsogenic actions, decreases salt appetite and lowers blood pressure. ANP may be of pathophysiological importance in several cardiovascular disorders such as congestive heart failure, paroxysmal supraventricular tachycardia and possibly also arterial hypertension. ANP seems to be a circulating hormone as well as putative neurotransmitter with important regulatory actions on salt and water homeostasis as well as blood pressure regulation.

Adrenal Cortex↗

Psychiatric care and course of psychiatric disorders from childhood to early adulthood in a representative sample.

The incidence and prevalence of registered and psychiatric disorders were studied from birth to 24 years of age in a total population. The cumulative incidence of psychiatric disorders (meeting DSM III criteria) below 25 years was 13.9% for boys and 14.2% for girls. The outcomes of psychiatric disorders during childhood were generally good. Only 11% of children with an onset before age 10 remained in psychiatric care as young adults. Psychiatric disorders were more common among boys who had attended special classes. Low intelligence was related to psychiatric disorders with an onset before 15 years of age in males, but after 15 in females.

Adolescent↗

Acute and long-term antihypertensive effect of bopindolol once daily or once weekly.

Fourteen male patients, mean age 53 years (range 35-64), were included in an initial 3 months' double-blind crossover study, in which 1-2 mg bopindolol, a nonselective beta blocker with intrinsic sympathomimetic activity (ISA), was compared with 100-200 mg metoprolol regarding effects on blood pressure and heart rate. During the subsequent long-term therapy, eight patients were trained to measure home blood pressure, and in these patients bopindolol 1 mg daily was compared to 8 mg once weekly in a double-blind fashion for 3 weeks on each regimen. Bopindolol (mean dose 1.35 mg/day) caused a significant blood pressure reduction, 26/15 mm Hg, as did metoprolol, 24/3 mm Hg (mean dose 144 mg/day) (NS). Supine and standing heart rates were reduced during both bopindolol and metoprolol treatment. During long-term therapy with bopindolol satisfactory blood pressure control was achieved for 1 year in 11 patients. Heart rate was significantly reduced after 2-3 months' treatment and during the entire 1-year follow-up. Few and well-tolerated side effects were reported. During treatment with bopindolol 8 mg once weekly, the blood pressure control was maintained satisfactorily over the week and no significant differences were observed in comparison with daily administration (1 mg) of the drug.

Adrenergic beta-Antagonists↗

Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide.

Blood pressure (BP) and metabolic variables were determined initially and after 1, 2, 4, 6 and 10 years' treatment in two groups of hypertensive men (n = 53 each) randomized to bendroflumethiazide 2.5-5 mg/day or propranolol 160-320 mg daily. There was no significant differences in BP or metabolic variables between the two groups at entry. BP was reduced to the same degree by both treatments. Five men in the propranolol group and one man in the thiazide group developed clinically overt diabetes during follow-up. Fasting blood sugar increased slightly but significantly though equally in both groups. Oral glucose tolerance was initially impaired to the same degree in both groups but improved significantly during treatment with both drugs. Fasting insulin increased slightly but to the same degree. While serum potassium decreased significantly in the thiazide group, the total body potassium was unchanged in this group. In the propranolol group, serum potassium rose, while total body potassium decreased significantly. Serum urate increased in both groups, though slightly more during thiazide treatment. One case of gout was found in each group. There was no difference in serum lipids between the two groups. The finding in this long-term trial indicate that in middle-aged men with mild to moderate hypertension a low-dose thiazide diuretic like bendroflumethiazide is as effective and safe an antihypertensive agent as the beta-blocker propranolol is and that it does not induce diabetes. The total clinical picture favors the retention of thiazide diuretics as a first choice drug in hypertension.

Bendroflumethiazide↗