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Biomedical subjects

G Karlsson

Publications and source records attributed to G Karlsson.

At least 91 records · Page 5Linked to original sources

Crystallization and preliminary crystallographic data for the azurin mutant End-121 from Pseudomonas aeruginosa.

Pseudomonas aeruginosa azurin has been crystallized from a mutant where residues from Met 121 to Lys128 have been deleted from the protein. The crystals form pale-blue well formed prisms in the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 60.79 (5), b = 123.47 (5), c = 187.77 (5) A. The crystals diffract to 3.0 A and there are eight molecules in the asymmetric unit.

Journal Article↗

Nasal congestion during the menstrual cycle.

Oestrogens have been considered to cause nasal congestion during the menstrual cycle and during pregnancy. The aim of the present study was to evaluate the degree of nasal congestion during the menstrual cycle in healthy women. Nasal peak expiratory flow (nPEF) was measured and subjective nasal stuffiness was scored morning and evening by 27 women for 3 months and by 14 women for 6 months. During the menstrual days, when the serum oestrogen level is lowest, the morning nPEFs were significantly lower compared with the rest of the cycle (P = 0.0012). The difference was most pronounced for the second day of the cycle (P = 0.00034). The correlation between nPEFs and the subjective scores was high (R = 0.98), while the coefficient of variation within the series of three nPEF recordings was low (6.4%). It is concluded that the nasal obstruction experienced during menstruation cannot be explained by increased serum levels of oestrogen.

Adult↗

Metachromatic, IgE-bearing and tryptase-containing cells on the nasal mucosal surface in provoked allergic rhinitis.

We studied the relationship between mast cells or basophils and symptoms in provoked allergic rhinitis. Nasal brush and lavage samples were obtained before nasal allergen challenge and every 2 h for 12 h after the challenge in 10 allergics and 3 controls. The cells were identified by their metachromatic staining properties (brush and lavage samples) or with immunohistochemical methods using specific antibodies to IgE and tryptase, a selective mast-cell marker (brush samples). Histamine was determined in the brush samples using liquid chromatography. After an initial decrease, the numbers of metachromatic, IgE-bearing and tryptase-containing cells, as well as the histamine content of the cells in the brush samples, increased during the subsequent observation hours. The prechallenge cell and histamine values correlated with the symptom score 15 min after the challenge. The prechallenge lavage samples lacked metachromatic cells, but these cells were found in increasing numbers after the provocation. Three of the patients differed from the remaining seven in that their prechallenge brush samples contained many positively stained cells. All patients showed a positive cellular response to the allergen challenge, but these three individuals showed the most vivid response. The morphology of the metachromatic cells in the prechallenge brush samples agreed with that of mast cells, but the morphology of metachromatic cells which outnumbered tryptase-containing cells in samples at 8 to 12 h rather agreed with their being basophils.

Adult↗

Sedatives and hypnotics in Stockholm: social factors and kinds of use.

OBJECTIVES: The aims of the study were (1) to estimate prevalence rates of current, regular, and long-term use of sedatives and hypnotics and the incidence of regular use in an urban population and (2) to study the association between such use of drugs and sociodemographic factors, symptoms of disease, and alcohol consumption. METHODS: Data on drug use in a random sample of 6217 adults in Stockholm County were analyzed with logistic regression. RESULTS: The prevalence rate for current use of sedatives or hypnotics was 12.8% among men and 18.6% among women; the rate for regular use was 3.7% among males and 4.7% among females. The odds ratio for current use increased with age and was higher among unemployed persons and disability pensioners, high consumers of alcohol, persons with an increased level of symptoms, and widows. More than 25% of the persons who had used sedatives or hypnotics during the previous 2 weeks were regular users 6 months later. For persons aged 25 through 64 years, the annual incidence rate was 1.8% among men and 2.7% among women. CONCLUSIONS: The comparatively low incidence and high prevalence of regular use implies that long-term use of sedatives and hypnotics is common.

Adolescent↗

Does allergic rhinitis predispose to sinusitis?

The relationship between allergic rhinitis and sinusitis is reviewed with regard to seasonal as well as perennial and fungal sinusitis. There seems to be some association between allergic processes in the nose and inflammation in the sinus mucosa but the available data are, to some extent, contradictory. Thus, the causative role of allergy in sinusitis is not clear. Prospective studies to further elucidate the influence of allergic inflammation in the pathogenesis of sinusitis are highly warranted.

Causality↗

Structure of Pseudomonas aeruginosai zinc azurin mutant Asn47Asp at 2.4 A resolution.

The Pseudomonas aeruginosa azurin mutant Asn47Asp has been isolated, its spectroscopic and kinetic properties characterized, and the X-ray crystal structure of its zinc derivative determined. While the optical and electron paramagnetic resonance spectra as well as the electron-transfer activity of the mutant are very similar to the wild-type values, the Asn47Asp reduction potential is slightly increased by 20 mV. The mutant crystallized in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 57.8, b = 81.5 and c = 112.6 A. There are four molecules in the asymmetric unit, packed as a tetramer which consists of two independent dimers. The zinc site of this mutant structure is similar to the wild-type zinc azurin and, in particular, the metal-binding site is almost identical to the site found in the wild-type zinc-azurin structure [Nar, Huber, Messerschmidt, Filippou, Barth, Jaquinod, Kamp & Canters (1992). Eur. J. Biochem. 205, 1123-1129]. The Asp47 side chain at that mutation site takes on a very similar orientation to Asn47 in the wild-type structure preserving the two hydrogen bonds with the neighbouring Thr113 NH and O(gamma)H. Therefore, the increased reduction potential of the mutant is probably a result of an altered charge distribution close to the metal site.

Journal Article↗

Outcome measurement in economic evaluations of growth factors.

There are several ways of measuring outcome in an economic evaluation of filgrastim therapy. These measures imply different types of economic evaluation. In all cases, the filgrastim therapy is compared with no filgrastim therapy. Since different therapeutic strategies are connected with uncertain consequences, decision trees are helpful analytical tools. The potential implications of different types of economic evaluations are illustrated with a simple decision tree.

Cost of Illness↗

Mast cells and mediators in the nasal mucosa after allergen challenge. Effects of four weeks' treatment with topical glucocorticoid.

The study focuses on the relationship between the tissue density of mast cells, the tissue histamine levels and the levels of markers of mast cell activation after an allergen challenge of the nasal mucosa of allergic patients. The effect of 4 weeks' treatment with a topical glucocorticoid, fluticasone propionate, was studied in a double-blind, placebo-controlled study of 25 hay fever patients. Nasal biopsies were obtained before and after the treatment period for the evaluation of mast cell density and tissue histamine levels. Nasal challenges were performed at 2-week intervals for 8 weeks using a standardized nasal lavage model. TAME-esterase was analysed in the returned lavage fluid from all the challenges (weeks 0-8), while the levels of histamine and tryptase were analysed in lavage fluids from challenges performed before and after the treatment period (weeks 0 and 4). The symptoms of nasal allergy were assessed after each challenge. Treatment with fluticasone propionate did not influence mast cell density, the tissue histamine concentration, the lavage histamine levels or the TAME-esterase activity, while a reduction in nasal symptoms and tryptase in nasal lavage fluid was revealed. Our present study again emphasizes the fact that the mast cell is an important trigger cell in the immediate nasal allergic response. The study also demonstrates the usefulness of the measurements of tryptase as an indicator of both mast cell activation and the efficacy of topical steroid treatment.

Administration, Topical↗

The prevalence of alcohol-related mortality in both sexes: variation between indicators, Stockholm, 1987.

OBJECTIVES: The purpose of this study was to analyze the prevalence rates of alcohol-related mortality--according to various indicators--in both sexes in Stockholm, Sweden. METHODS: A study of alcohol involvement at death was undertaken for all 668 deceased persons aged 15 through 54 years in 1987 in Stockholm. Death certificates, autopsy information, police records, and information about earlier conviction were analyzed. RESULTS: When different measures of estimation were compared, there were great differences in the prevalence rates of alcohol involvement. According to the death certificates, 9.2% of the males and 11.2% of the females had alcoholism, alcohol intoxication, pancreatitis or liver cirrhosis as underlying cause of death. When all accessible information was used, potential alcohol involvement was found in 57.5% of the male and in 32.2% of the female deaths. There was a marked association between earlier drunken driving and alcohol involvement. After reevaluation of the diagnoses with autopsy findings, the number of cases with cardiac enlargement and suspected cardiomyopathy increased from 10 to 62. CONCLUSION: The results point to the serious underdiagnosis of alcohol involvement in death certificates and the misclassification of important causes of death (i.e., liver cirrhosis and cardiac disease); they also call for increased efforts regarding prevention.

Adolescent↗

Blockade of GABAB receptors accelerates amygdala kindling development.

The aim of this study was to investigate the putative role of GABAB receptors in the development of amygdala kindling in rats. The effects of the GABAB blocker CGP 35348 and the GABAB agonist baclofen on the progressive development of behavioural seizure symptoms (stages 1-5 classified by Racine) and duration of after-discharges (AD) were studied. CGP 35348 at a dose of 300 mg/kg i.p., which blocks central GABAB receptors, moderately but consistently accelerated the development of behavioural seizure symptoms. CGP 35348 had no marked effect on the duration of ADs corresponding to the different seizure stages. L-baclofen (6 mg/kg i.p.) had a dual effect on kindling development. It retarded the development of the behavioural symptoms, but increased the duration of AD. In conclusion, the results suggest that synaptically-released GABA activated GABAB receptors and thereby exerted a depressant effect on kindling development.

Amygdala↗

Mast cells and eosinophils in the allergic mucosal response to allergen challenge: changes in distribution and signs of activation in relation to symptoms.

An allergen challenge was performed in 10 asymptomatic patients with strictly seasonal allergic rhinitis. For comparison; seven nonallergic subjects were challenged with allergen, and seven allergic patients were challenged with diluent. Cell samples, obtained with use of a brush technique to recover cells from within the epithelium and nasal lavage to collect cells from the epithelial surface, and symptom scores were taken before challenge and at 2-hour intervals during 12 hours. The cell suspensions were cytocentrifuged onto object slides for light microscopy. Histamine was determined in the cell pellets. In brush samples from the allergic patients challenged with allergen, eosinophils, expressed as a percentage of the total granulocytes, increased from 4.3% +/- 2.7% (mean +/- SEM) to 10.3% +/- 3.8% (p < 0.05) 4 hours after challenge. This level was maintained for up to 12 hours. A similar increase was noted in the lavage specimens 2, 6, and 8 hours after the challenge. In the brush samples the proportion of eosinophils containing two or more cytoplasmic vacuoles, taken as a sign of activation, increased from 20% to 72% (p < 0.05) 8 hours after provocation. In brush samples from the allergic patients challenged with allergen, the numbers of metachromatic cells increased to a maximum of eightfold at 10 hours. In the lavage specimens, no metachromatic cells were observed before provocation, but they progressively increased in number 2 to 12 hours after provocation. Cell pellet histamine content decreased temporarily 2 to 4 hours after challenge (p < 0.05) in brush samples from allergen-challenged allergic patients. The local metachromatic cell density before challenge, as reflected in the brush specimens, correlated with nasal congestion, sneezing, and the degree of eosinophilia.

Adult↗

GABAB receptors in various in vitro and in vivo models of epilepsy: a study with the GABAB receptor blocker CGP 35348.

The effect of the GABAB receptor blocker CGP 35348 on epileptic processes in vitro and in vivo was studied. In hippocampal slices of the rat maintained in vitro, CGP 35348 (100 microM) induced a moderate increase in the frequency of extracellularly recorded spontaneous epileptiform burst discharges induced in CA3 by penicillin (1.2 mM), bicuculline (5 microM) and low Mg(2+) (0.1 mM). This effect was observed in 50-75% of the slices. A similar but less consistent increase was also observed in CA1 in bicuculline and low Mg2+. Data obtained by intracellular recordings from CA1 pyramidal cells in the presence of bicuculline (10 microM) demonstrated that CGP 35348 (100 microM) increased the duration of the paroxysmal depolarization underlying an evoked epileptiform burst and reduced the early component of the after hyperpolarization which followed the burst. In mice pretreated with isoniazid, CGP 35348 (300 mg/kg, i.p.) significantly increased the number of convulsing mice. However, convulsions induced by submaximal doses of pentylenetetrazol, picrotoxin or strychnine were not facilitated by CGP 35348. We conclude that GABAB receptors appear to exert a suppressant effect on various kinds of epileptiform discharges of hippocampal neurons in vitro. In vivo, however, the role of GABAB receptors in regulating convulsions is less prominent since only isoniazid-induced convulsions were facilitated by GABAB receptor blockade.

Animals↗

The relationship between stressful working conditions and high alcohol consumption and severe alcohol problems in an urban general population.

The relationship between 15 measures of stressful working conditions and high alcohol consumption (35 g 100% ethanol per day or more for men and 25 g or more for women) was studied, using cross-sectional data from a general population survey of 1344 males and 1494 females; the ages 25-64 years in metropolitan Stockholm in 1984. In a longitudinal component of the study, hospitalization and mortality with alcohol-related diagnosis was assessed during 1984-90, and also the association between previous experience of unemployment and high alcohol consumption. Some of the associations, expressed as age-adjusted odds ratios, were positive and some were negative when high alcohol consumption was the endpoint, but there was a clear variation by sex and social class. Generally the positive associations were stronger among male non-manual employees. Among males, there was a clear association between stressful working conditions and subsequent risk of severe medical alcohol-related problems, but the precision of the estimates was low due to low number of cases. The odds ratio was 6.18 (95% confidence interval 1.86, 20.61) for twisted working positions and 6.74 (95% confidence interval 1.67, 27.19). Previous unemployment among males was associated with increased risk for high alcohol consumption, with an odds ratio of 5.71 (95% CI 1.39, 15.97) among those who had been unemployed more than once, and 1.67 (95% CI 0.76, 3.64) among those who had been unemployed once during the previous 5 years. Those and other increased odds ratios were lower when subjects with an alcohol diagnosis at inpatient care during 1980-84 were excluded in the analyses. On the whole, our findings are not conclusive. The strong, but imprecise associations between stressful working conditions and severe alcohol problems, are however challenging, and warrants further studies, preferably with longitudinal design and repeated measurements of both working condition and alcohol habits.

Adult↗

Clinical efficacy of budesonide in the treatment of eczematous external otitis.

Sixty patients with mild to moderate forms of eczematous otitis externa were treated with budesonide and placebo in a double-blind controlled study using parallel groups. Each treatment period was preceded by otomicroscopic examination and thorough cleaning of the ear canal. The symptoms and signs were assessed with a score system ranging from 0 (no symptoms/signs) to 3 (severe symptoms/signs). Budesonide treatment was associated with a reduction in severity of all symptoms recorded and a marked improvement in erythema, swelling and discharge. Mechanical cleaning of the ear canal and placebo was not a sufficient treatment for this group of patients.

Administration, Topical↗