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Biomedical subjects

U Johansson

Publications and source records attributed to U Johansson.

81 records · Page 5Linked to original sources
PubMed1984

Correlation between chemical structure, receptor binding, and biological activity of some novel, highly active, 16 alpha, 17 alpha-acetal-substituted glucocorticoids.

The affinity for the glucocorticoid receptor in rat skeletal muscle of some glucocorticoids with a new type of 16 alpha, 17 alpha-acetal substituent has been estimated and correlated to the glucocorticoid activities in three in vivo systems in rats. Budesonide (an approximately 1:1 mixture of the C(22) epimers of 11 beta, 21-dihydroxy-16 alpha, 17 alpha-[(22R,S)-propylmethylenedioxy]-pregna-1,4-diene-3,20-dione) and the isolated (22R)- and (22S)-epimers bound to the same binding site as the potent glucocorticoids dexamethasone (DEX) or triamcinolone 16 alpha, 17 alpha-acetonide (TA), but with even higher affinity than DEX or TA, despite the lack of a 9 alpha-fluoro atom in budesonide and its epimers. The (22R)-epimer was twice as active as the (22S)-epimer, 4 times more active than TA, and 14 times more active than DEX. The introduction of a 9 alpha-fluoro atom slightly decreased the binding affinity of the (22R)-epimer of budesonide, in contrast to the positive effect of 9 alpha-fluorination of, e.g., 16 alpha, 17 alpha-acetonides. The negative influence of 9 alpha-fluorination of the (22R)-epimer was partially reversed in the 6 alpha, 9 alpha-difluorinated (22R)-epimer. Nevertheless, the fluorinated compounds were more active than DEX and TA (8 and 11 times more active than DEX, and 2 and 3 times more active than TA, in case of the 9 alpha-fluoro- and 6 alpha, 9 alpha-difluoro-derivatives of the (22R)-epimer, respectively). Budesonide is metabolized mainly to 16 alpha-hydroxyprednisolone (11 beta, 16 alpha, 17 alpha, 21-tetrahydroxy-pregna-1,4-diene-3,20-dione) and 6 beta-hydroxy-budesonide. Both metabolites were very weak competitors for the ligand-binding sites on the receptor (3% and 6% of the affinity of DEX, respectively). The affinity for the receptor in vitro was closely correlated to the topical glucocorticoid activity in vivo for the 12 steroids compared (r = 0.98; R = 0.98), which supports the contention that in vitro tests for receptor affinity are useful when screening for agonists among steroids with the present type of structures. The results on receptor-ligand interaction are in accordance with X-ray crystallographic data available for some steroids.

Animals↗
PubMed1983

A versatile localization system for microscopic multiparametric analysis of cells.

A new, simple and relatively inexpensive electronic digital position readout (DPRO) system which can be applied to the rapid localization and recovery of microscopic material is described. It is based upon a commercially available digital position readout system which is routinely utilized by industry for small machine tools and measuring equipment. This has been mounted onto the stage of various microscopic instrumentation to provide X and Y coordinates relative to an arbitrary reference point. The integration of small computers interfaced to scanning interferometric, microdensitometric and fluorescence microscopes were used to demonstrate the reliability, versatility and ease of application of this system to problems of multiparametric measurements and analysis of cultured cells. The system may be expanded and applied to clinical material to obtain automatized, multiparametric measurements of cells in haematology and clinical cytology.

Cells, Cultured↗
PubMed1982

Desensitization by terbutaline of beta-adrenoceptors in the guinea-pig soleus muscle: biochemical alterations associated with functional changes.

1 The effects of adrenaline and terbutaline on cyclic adenosine 3',5'-monophosphate (cyclic AMP) content, 22Na-efflux, 42K-influx and subtetanic contractions have been assessed in soleus muscles isolated from guniea-pigs which had been maintained on food with or without terbutaline for 5 days. 2 Terbutaline and adrenaline increased cyclic AMP content and suppressed subtetanic contractions, and regression analysis indicates a statistically significant correlation between these two effects (P less than 0.01). 3 In muscles obtained from terbutaline-treated animals, the effects of terbutaline and adrenaline on cyclic AMP content, active Na-K-transport and subtetanic contractions were all considerably suppressed, but insulin stimulated 22Na-efflux and affected subtetanic contractions to the same extent as in the muscles obtained from the control group. 4 The results suggest that terbutaline treatment leads to a reduction in the number of beta 2-adrenoceptors in skeletal muscle or an impairment of their function. 5 The results provide further support for the idea that the effect of adrenaline or insulin on skeletal muscle contractions is the outcome of stimulation of active Na-K-transport.

Animals↗
PubMed1982

Dissociation between the effects of some xanthine derivatives on the tracheal smooth muscle and on the skeletal muscle.

The ability of some xanthine derivatives to relax the trachea, contracted by pilocarpine, and to increase the force of contraction of directly stimulated skeletal muscles from the guinea-pig was studied in vitro. No relationship was found between these two effects. Relaxation of the trachea occurred at lower concentrations and with a different order of potency as compared with the effects on the slow-contracting soleus muscle or on the fast-contracting extensor digitorum longus. One of the compounds, IBMX, 1-methyl-3-isobutyl-xanthine, showed an isoprenaline-like effect on the soleus muscle i.e. it depressed the force and fusion of subtetanic contractions. The relaxing effect of theophylline and IBMX on the trachea was additive to that of terbutaline but no clear potentiation was observed. The depression of the contraction of the soleus muscle elicited by terbutaline was reinforced by IBMX but not by theophylline. Theophylline in concentrations which used alone enhanced the contractions of the soleus muscle inhibited the effect of terbutaline. We conclude that the relative contribution of the various effects of xanthine derivatives differs from compound to compound.

1-Methyl-3-isobutylxanthine↗
PubMed1981

beta 1-Adrenoceptors mediating relaxation of the guinea-pig trachea: experiments with prenalterol, a beta 1-selective adrenoceptor agonist.

In the presence of 17 beta-oestradiol, prenalterol, a beta-selective adrenoceptor agonist, caused a dose-dependent relaxation of the isolated, pilocarpine-contracted guinea-pig trachea. This effect was blocked by the antagonists propranolol (non-selective) and practolol (beta 1-selective) but not by IPS 339 [(t-butylamino-3-ol-2-propyl)oximino-9-fluorene HCl] (beta 2-selective). The relaxing effect of terbutaline, a beta 2-selective adrenoceptor agonist, was more efficiently blocked by IPS 339 than by practolol. These data support the hypothesis that the guinea-pig trachea contains both beta 1- and beta 2-adrenoceptors mediating relaxation and that the beta 1-adrenoceptors are selectively stimulated by prenalterol. The efficacy of prenalterol was less than that of terbutaline, thus confirming its partial agonistic activity. In the absence of 17 beta-oestradiol, the ability of prenalterol to relax the pilocarpine-contracted trachea was lost. It is suggested that 17 beta-oestradiol may act as a functional antagonist to pilocarpine as it caused a partial relaxation itself.

Adrenergic beta-Agonists↗
PubMed1980

Radioenzymatic determination of epinephrine, norepinephrine and dopamine in 0.1 ml plasma samples: plasma catecholamine response to submaximal and near maximal exercise.

A sensitive enzymatic isotope derivative method for simultaneous determination of epinephrine, norepinephrine, and dopamine in 0.1 ml plasma samples is described. The assay consists basically of 1. conversion of epinephrine, norepinephrine, and dopamine into their respective methyl-derivates in the presence of catechol-O-methyltransferase and S-adenosylmethionine-[3H]methyl, 2. extraction of the methylated 3H labelled amines with diethyl ether, 3. separation by thin-layer chromatography, 4. measurement in a beta radiation scintillation counter. The effect of standing upright and of submaximal and near-maximal steady state exercise on plasma epinephrine, norepinephrine, dopamine and plasma renin was studied in 16 young adults aged 22 to 34 years and 9 physically well trained boys 16-17 years old. Standing upright for 2 min did not results in significant changes in either epinephrine, norepinephrine, dopamine or plasma renin activity compared with supine (basal) values. During exercise, epinephrine, norepinephrine, dopamine and plasma renin activity increased exponentially with the work load, peak values being attained at the highest load or immediately after cessation of exercise. The respective maximal values for plasma renin activity and epinephrine and norepinephrine levels were approximately 3, 6 and 10 fold higher than basal values in the adults, and rose as high as 4, 10 and 20 fold in the boys. Peak dopamine values were only 2-3 times higher than the basal values in both adults and boys. It is concluded that the method described provides a suitable tool for a quantitative assessment of adreno-sympathetic tone during physiological and pathophysiological conditions.

Adolescent↗
PubMedDate not supplied

Bacteriological characterization of the effusion material in an animal model for serous and purulent otitis media.

By means of cleaving the soft palate and blocking the Eustachian tube, two otomicroscopically well defined types of otitis media, serous and purulent, were created in an animal model (rat). The microbiological pattern of these conditions were characterized at 1, 2, 3, 4 and 6 weeks after the onset. Samples were collected from the middle ear cavity via the bulla tympanica and cultured for aerobic as well as anaerobic bacteria. The serous effusion was culture-negative. The purulent effusion material was culture positive, and mixed with Gram-positive (S. aureus, S. epidermidis, Strept. faecalis) and Gram-negative (E. coli, Proteus mirabilis) bacteria of which the latter dominated. No anaerobic species were detected. The study shows that the two otomicroscopically different types of otitis media also differ with regard to the microbiological pattern. The rat thus provides the opportunity to study these two different inflammatory middle ear responses--infectious and noninfectious--during standardized conditions.

Animals↗
PubMedDate not supplied

Improved method for assay of estradiol and progesterone receptors with special reference to breast cancer.

Isoelectric focusing of estradiol receptor (ER) and multiple point dextran-coated charcoal (DCC) technique for progesterone receptor (PgR) were adapted for assay of both receptors in the same cytosol sample. Technical improvements and increased recovery of receptors were achieved. 1.0 fmol/ml cytosol of ER may be detected; sensitivity of PgR was 5-10 fmol/ml cytosol. Quantitation of ER was made in 414 (95%) out of 434 consecutive breast cancers. Inclusion of isoelectric focusing records showing only qualitative indication for presence of ER resulted in 98% ER containing tumours, supporting the aspect that strictly ER negative tumours are a rarity. Implications for therapy in disseminated disease are discussed.

Animals↗