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Biomedical subjects

K Larsson

Publications and source records attributed to K Larsson.

At least 235 records · Page 13Linked to original sources
PubMed1988

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↗
PubMed1988

Posture-induced airflow limitation in asthma: relationship to plasma catecholamines and an inhaled anticholinergic agent.

Postural influence on ventilatory function was investigated in thirteen asthmatic subjects on three consecutive days starting at 10.00 am. Lung function was measured in the seated position before and after four hours lying supine. Peak expiratory flow (PEF) was measured every 0.5 h in the supine position. Blood samples for determination of plasma catecholamines were collected before, during and after lying supine. After the initial lung function testing, placebo or ipratropium bromide (0.125 mg) was inhaled. On the third day the whole trial was performed seated, without any drug, as a control experiment. On the placebo day lying supine induced an initial, rapid fall of PEF followed by a progressive decrease during the four hours. The progressive decrease in PEF was apparently caused by bronchoconstriction. Ipratropium bromide prevented this posture-induced bronchoconstriction. On the day seated there was also a tendency towards a decline of PEF though less pronounced than in the supine position on the placebo day. No significant alterations in plasma levels of catecholamines were observed. We conclude that the supine posture is a stimulus to bronchoconstriction in asthma, likely to be involved in nocturnal wheezing. Postural bronchoconstriction is not explained by lowered plasma levels of adrenaline, as has been suggested for nocturnal asthma. The results raise the question of whether cholinergic mechanisms are involved.

Acute Disease↗
PubMed1987

Region-selective activation of brain monoamine synthesis by sexual activity in the male rat.

In vivo catecholamine and 5-HT synthesis during sexual activity and treadmill locomotion was estimated in male rats by measuring the accumulation of DOPA and 5-HTP after inhibition of cerebral aromatic amino acid decarboxylase by means of NSD-1015 (100 mg.kg-1 i.p.). An increase in catecholamine as well as 5-HT synthesis during sexual activity was observed in both the neostriatum and the nucleus accumbens. An increase in catecholamine synthesis during treadmill locomotion was found in the neostriatum only. No significant changes in monoamine synthesis were found in the septal area or in the anterior hypothalamus.

Animals↗
PubMed1987

Structure of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the pi subunit.

The class II enzyme of human liver alcohol dehydrogenase was isolated, carboxymethylated, and cleaved with CNBr and proteolytic enzymes. Sequence analysis of peptides established structures corresponding to the pi subunit. Two segments from the C-terminal region unique to pi were selected for synthesis of oligodeoxyribonucleotide probes to screen a human liver cDNA library constructed in plasmid pT4. Sequence analysis of two identical hybridization-positive clones with cDNA inserts of about 2000 nucleotides gave the entire coding region of the pi subunit, a 61-nucleotide 5' noncoding region and a 741-nucleotide 3' noncoding region containing four possible polyadenylation sites. Translation of the coding region yields a 391-residue polypeptide, which in all regions except the C-terminal segment corresponds to the protein structure as determined directly by peptide analysis. With the class I numbering system, the exception concerns a residue exchange at position 368, the actual C-terminus which is Phe-374 by peptide data but a 12-residue extension by cDNA data, and possibly two further residue exchanges at positions 303 and 312. The size difference might indicate the existence of posttranslational modifications of the mature protein or, in combination with the residue exchanges, the existence of polymorphism at the locus for class II subunits. The pi subunit analyzed directly results in a 379-residue polypeptide and is the only class II size thus far known to occur in the mature protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗
PubMed1987

Molecular cloning and characterization of a full-length cDNA clone for human plasminogen.

A human liver cDNA library enriched for full-length clones was screened for plasminogen cDNA using a synthetic 24-nucleotide probe derived from a reported partial cDNA sequence. 12 positive clones were identified and one of these was characterized in detail. The 2.7 kb insert contains the complete coding region. At 5 positions, it gives residues different from those reported in a previous amino acid sequence analysis of the protein. The present results show an extra Ile at position 65, Gln instead of Glu at positions 53 and 342, Asn at position 88 instead of Asp, and Asp at position 453 rather than Asn. In the 3'-non-coding region an extension of 29 bases is found which does not contain any structure compatible with a known polyadenylation signal. Instead, the consensus signal AATAAA is placed at a distance of 46 bases upstream of the poly(A)-tail.

Amino Acid Sequence↗
PubMed1987

Separation of dopaminergic and serotonergic inhibitory mechanisms in the mediation of estrogen-induced lordosis behaviour in the rat.

The administration of the putative 5-hydroxytryptamine1 (5-HT1) agonist 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) (0.0625-1.0 mg X kg-1) suppresses lordosis behaviour induced in ovariectomized female rats by daily treatment for 3-5 days with estradiol benzoate (1.25 micrograms/rat). A similar suppressive effect on the lordosis behaviour can be obtained by administration of the dopamine/serotonin agonist, lisuride (0.1-0.4 mg X kg-1), or after the administration of the dopamine (DA) agonists, apomorphine (0.2-0.8 mg X kg-1) or quinpirole (0.75-2.50 mg X kg-1). The suppressive effects on the lordosis behaviour by 8-OH-DPAT cannot be antagonized by the DA receptor antagonist haloperidol (0.2 mg X kg-1) neither with methiotepin (0.5 mg X kg-1), which is assumed to be a non-selective 5-HT receptor blocking agent, nor with pirenperone (0.25 mg X kg-1) which is assumed to be a 5-HT2 receptor blocking agent. However, a partial blockade of the lordosis suppressive effects of 8-OH-DPAT was obtained by treatment with (-)-pindolol, which is thought to be a partial 5-HT1 blocking agent, suggesting that 8-OH-DPAT exerts its suppressive effects on the lordosis behaviour through the 5-HT system. Haloperidol causes a complete blockade of the suppressive effects of apomorphine and quinpirole suggesting that these drugs exert their inhibitory effects on the lordosis behaviour by activating the DA system.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Studies in vivo and in vitro of terbutaline-induced beta-adrenoceptor desensitization in healthy subjects.

Beta-Adrenoceptor function was studied in eight healthy subjects before, during and 24 and 72 h after cessation of 2 weeks continuous oral treatment with the beta 2-adrenoceptor agonist terbutaline (sustained release, 7.5 mg twice daily). In vivo, blood pressure, heart rate, plasma noradrenaline and plasma cyclic AMP responses to isoprenaline (0.01, 0.02 and 0.05 microgram min-1 kg-1 intravenously) were related to the plasma concentrations of isoprenaline. for comparison, beta 2-adrenoceptor function was evaluated in lymphocytes in vitro by studies of isoprenaline-induced accumulation of cyclic AMP and radioligand binding studies using 125I-iodohydroxybenzylpindolol. In vivo, the beta 2-mediated plasma cyclic AMP response to isoprenaline was markedly attenuated during terbutaline treatment and was still reduced by 38% (P less than 0.05) 72 h after discontinuation of treatment. The blood pressure and heart rate responses to isoprenaline were unaffected by treatment. Isoprenaline-induced elevations of plasma noradrenaline concentrations were markedly reduced during terbutaline treatment. This indicates an attenuation of isoprenaline-induced increases in sympathetic nerve function and could explain why no attenuation of the isoprenaline-induced vasodilatation was observed. Thus, plasma cyclic AMP seems to be a better marker than diastolic blood pressure when evaluating beta 2-adrenoceptor responsiveness in vivo in man, since it is not influenced by counter-regulatory increases in sympathetic nerve activity and/or noradrenaline overflow from sympathetic nerves. In lymphocytes, the isoprenaline-stimulated cyclic AMP accumulation was reduced by 75% and the beta-adrenoceptor binding sites were reduced by 40% 12 h after dosing. Also the lymphocyte beta 2-adrenoceptors recovered slowly after withdrawal of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Learning effects, variation during office hours and reproducibility of static and dynamic spirometry.

Static and dynamic spirometric tests were performed in 21 healthy subjects (21-61 years old, 8 smokers and 9 ex-smokers) on 3 different days within 2 weeks. The design of the study allowed separation of the influence of learning and diurnal changes between 09.00 and 17.00 h. In addition, the reproducibility of the tests and the effect of inhalation of 2.5 mg of terbutaline sulphate were studied. No learning effect was observed. There were slight, but statistically significant differences between morning, noon and afternoon measurements. Thus, the residual volume and flow in the early phase of forced expiration were highest in the afternoon, while maximal voluntary ventilation was lower at noon than in the afternoon or morning. The intraindividual variabilities (defined as standard deviation of difference between first and second measurement) of total lung capacity, vital capacity and forced expiratory volume in 1 s (FEV1) were about 3% of the predicted values. The ratio of intra- to interindividual variability was 0.2-0.3. The remaining tests showed higher variability and a higher intra- to interindividual variability ratio. Terbutaline inhalation caused a significant increase in most forced expiratory flow variables. A 10% increase in FEV1 corresponded to a 50-60% increase in endexpiratory flow. In spite of this, the endexpiratory flow and mean transit time were better discriminators of the effects of bronchodilation in normal subjects.

Adult↗
PubMed1987

Ipratropium bromide: bronchodilator action and effect on methacholine-induced bronchoconstriction.

The effects of ipratropium bromide (80 and 200 micrograms) and placebo on the basal bronchial tone and on methacholine-induced bronchoconstriction were investigated in 10 asthmatic patients in a placebo-controlled double-blind manner. Bronchial hyperreactivity to methacholine was confirmed at a pretrial bronchial challenge. The patients were randomly allocated to two groups in which the drug was inhaled from either metered-dose inhalers (MDI) or powder capsules. With the high dosage, the bronchodilation resulting from powder capsules was somewhat more pronounced than that achieved with the MDI. Otherwise the bronchodilator effect of ipratropium bromide and the protection afforded by the drug against methacholine-induced bronchoconstriction were similar in the two groups. In five patients the bronchodilator effect was better and in four patients the tolerance to methacholine was greater after the higher ipratropium dosage than after the lower one. In two patients ipratropium bromide had no bronchodilator effect but gave good protection against methacholine-induced bronchoconstriction. It is concluded that some patients benefit from a dosage of ipratropium bromide higher than that usually recommended and that an anticholinergic effect on the bronchi is possible even in the absence of the bronchodilator effect in the basal state.

Administration, Inhalation↗
PubMed1987

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↗
PubMed1986

The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties.

cDNA clones corresponding to two alleles of the ADH3 locus were identified by hybridization with synthetic oligodeoxyribonucleotides specific for class I human liver alcohol dehydrogenase. Sequences were determined for a 1457-nucleotide cDNA, covering the whole gamma 2-coding region, and a 1224-nucleotide cDNA, including the region coding for amino acid residues 53-374 of the gamma 1 subunit. Two amino acid replacements between the gamma 1 and gamma 2 subunits were identified. At position 349, isoleucine in gamma 1 instead of valine in gamma 2 is a conservative exchange of a superficial residue which has been ascribed no special importance. The other exchange, at position 271, arginine in gamma 1 and glutamine in gamma 2, explains differences in enzyme properties. Electrophoretically, it is consistent with the less cathodic mobility of the gamma 2 subunit. Functionally, the location of the exchange at the surface of the coenzyme-binding pocket may influence the dissociation of the reduced coenzyme.

Alcohol Dehydrogenase↗
PubMed1986

Improvement of the isoprenaline infusion test by plasma concentration measurements.

A simple and sensitive method for the determination of isoprenaline (ISO) in plasma by high performance liquid chromatography (HPLC) with electrochemical detection is presented. Blood pressure and heart rate responses to i.v. infusion of ISO (15, 38 and 76 ng/kg/min) were studied in 15 subjects. Blood samples for ISO analyses were drawn after 7.5 min infusions on each dose level. A four- to six-fold interindividual variation in the venous plasma concentrations of ISO was found. Comparisons were made between estimates of the sensitivity to ISO from concentration-effect and dose-effect curves for both heart rate and diastolic blood pressure responses. Despite an overall correlation between the two methods of estimating ISO sensitivity, individual estimates of sensitivity differed markedly due to the differences in the plasma concentrations attained during infusions of standardized doses of ISO. The venous plasma concentration of ISO required to elevate heart rate by 25 beats/min (CC25) varied between 0.3 and 1.7 nM, whereas the corresponding dose of ISO (CD25) varied between 10 and 27 ng/kg/min.

Blood Pressure↗
PubMed1986

Suppression of lordosis behavior by the putative 5-HT receptor agonist 8-OH-DPAT in the rat.

The administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), inhibited the lordosis induced by estradiol benzoate or estradiol benzoate plus progesterone in ovariectomized rats. There was no facilitation of lordosis by 8-OH-DPAT in animals pretreated with a threshold dose of estradiol benzoate. The results are consistent with the view that 8-OH-DPAT is an agonist at 5-HT receptors and provide further support for an inhibition role of central 5-HT in the mediation of lordosis behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

cDNA and protein structure for the alpha subunit of human liver alcohol dehydrogenase.

Two cDNA clones for human liver alcohol dehydrogenase (ADH) were identified, together covering 1450 nucleotides that contain the cDNA sequence of the ADH1 locus and include a coding region of 1122 nucleotides for the alpha subunit of the enzyme. In parallel, direct peptide analyses of the carboxymethylated protein also established most of the amino acid sequence. Nucleotide and peptide data were in complete agreement and show exchanges at 24 positions in the alpha relative to the beta subunit. One of the cDNA clones had a 139-nucleotide internal deletion at a position of possible interest in relation to mRNA processing, ancestral connections, or DNA replication. The structure of the alpha subunit is homologous to that of the beta and gamma subunits but has many exchanges, also of functionally important residues, explaining the different enzymatic properties. In total, 35 of 374 amino acid residues differ between the class I isozymes, and the substitutions add an extra SH group in the alpha subunit. Only in the beta-pleated sheet region of the coenzyme-binding domain is almost complete lack of substitutions noted, illustrating the importance of this region. In contrast, the active site region is far less conserved. However, similar exchanges of functional significance have also been found in distantly related alcohol and polyol dehydrogenases.

Alcohol Dehydrogenase↗
PubMed1986

cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions.

Three different size classes of cDNA clones coding for the beta 1-subunit of human alcohol dehydrogenase (ADH) were characterized from a human liver cDNA library. Clones were identified by hybridization with synthetic oligodeoxyribonucleotides. A total of 2530 nucleotides were determined, covering an ADH-coding region of 1122 nucleotides, a preceding 72-nucleotide segment and 3 types of 3'-non-coding region. The coding nucleotide sequence is in full agreement with the amino acid sequence of the beta 1-subunit. Of 8 clones identified, 6 had a short, 213-nucleotide 3'-non-coding region; 1 an intermediate, 590-nucleotide 3'-region; and 1 a long, 1330-nucleotide 3'-region. In addition, 2 unused polyadenylation signals were found. These results suggest that human liver beta-ADH mRNAs occur in several size classes, and that in addition to the consensus sequence AATAAA further signals are important for 3'-end formation.

Adult↗
PubMed1986

Internal chain cleavage and product heterogeneity during Edman degradation of isosteric peptide analogs lacking the alpha-carbonyl function.

A synthetic peptide analog, with one peptide carbonyl group replaced by a methylene bridge, was submitted to structural analysis by Edman degradation. Multiple cleavages were obtained in the first cycle, due to phenylthiocarbamylation of the internal secondary amine as well as spontaneous alkaline cyclization and subsequent recoupling with the Edman reagent. Three fragments from cleavage of the peptide analog after a single Edman cycle were purified by reverse-phase high-performance liquid chromatography. The results support previous observations in a novel combination. The reactions may also be important with native polypeptides since non-quantitative alkaline cyclization now encountered can mimic apparent N-terminal heterogeneity in agreement with earlier data, while quantitative cyclization can mimic loss of N-terminal residues.

Alkylation↗