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Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 397 records · Page 22Linked to original sources
PubMed1987

(+)-cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin: a potent and highly stereoselective 5-hydroxytryptamine receptor agonist.

C1-Methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1) were synthesized and tested for central 5-HT and dopamine receptor activity by use of a biochemical test method in rats. cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin (8) was found to be a 5-HT receptor agonist. The (+)-enantiomer of 8 had a potency equal to that of 1, whereas (-)-8 and the trans isomer (+/-)-9 were inactive.

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

N-substituted 1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines and 3-phenylpiperidines: effects on central dopamine and sigma receptors.

N-Substituted analogues of trans-7- and trans-9-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline (trans-7- and trans-9-OH-OHBQ) were tested for dopamine (DA) D2 receptor affinity by using in vitro [3H]spiperone and in vivo 5,6-di-n-Pr-ADTN binding assays. Potencies at central pre- (auto-) and postsynaptic DA receptors were determined by a biochemical and a behavioral method, respectively. Corresponding data were included for analogous, resolved 3-(3-hydroxyphenyl)piperidines and a few other substituted, racemic 3-phenylpiperidines. Beside the central dopaminergic effects of these compounds, previously reported sigma receptor affinity data [[3H]-(+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine; [3H]-(+)-3-PPP] were also taken into account for a comparison of the structure-activity/affinity relationships of these compounds at these two receptor types. Larger N-substituents in both phenylpiperidines and OHBQs increase both pre- and postsynaptic dopaminergic activity. An n-propyl group gives high dopaminergic efficacy at both receptor sites (pre- and postsynaptic) in all series. However, even higher dopaminergic potency is observed for trans-7-OH-OHBQs and (S)-3-(3-hydroxyphenyl)piperidines with N-substituents larger than n-propyl. In contrast, trans-4-n-Bu-9-OH-OHBQ is inactive, and (R)-3-(3-hydroxyphenyl)-N-n-butylpiperidine is less active at central DA receptors than its corresponding n-propyl analogue. This implies interesting differences in N-substituent sensitivity for the different classes of compounds with respect to the direction of their respective N-substituents at the drug-receptor interaction. The stereochemical and steric demands for sigma receptor affinity are much less stringent. The general trend is that, up to a certain size, the more lipophilic the N-substituent, the higher the affinity for sigma receptor sites.

Animals↗
PubMed1987

Dichotic listening and reading acquisition in children: a one-year follow-up.

Two dichotic listening experiments on hemispheric asymmetry and reading acquisition in children are reported. In the first experiment, 60 eight-year-old children were divided into three groups with different levels of reading acquisition. In order to separate attentional factors from hemisphere factors, all subjects were requested to attend to and report only the right-ear input in one third of the trials, to attend to the left-ear input in one third, and to be free to divide attention either way in one third. The results showed an expected right-ear advantage (REA) in all groups during the forced-right, and nonforced recall conditions. However, a REA was also found during the forced-left recall condition for subjects less advanced in reading. The same children were followed-up 1 year later in a second experiment. The results showed that the REA during the forced-left condition for the less advanced subjects in Experiment 1 was in essence shifted to a left-ear advantage (LEA) in Experiment 2. The relationships of attentional factors in hemispheric asymmetry and reading acquisition are discussed.

Attention↗
PubMed1987

ACTH-mediated aldosterone hypersecretion during endotoxin-induced fever with apparent influence upon renal sodium excretion.

Febrile, endocrine, and renal responses to i.v. injection of endotoxin (E. coli lipopolysaccharide, 0.25 microgram kg-1) were studied in hyperhydrated goats without, and after dexamethasone pre-treatment, performed with the aim of inhibiting the adenohypophyseal secretion of ACTH. As expected from previous investigations, the administration solely of endotoxin induced biphasic fever, pronounced and long-lasting (less than 4 h) elevation of plasma cortisol (PC), and a prompt inhibition of the water diuresis. Apparently the observation that endotoxin also induced a pronounced biphasic elevation of plasma aldosterone (PA) where the two rising phases coincided with the early, and respectively the second elevation in rectal temperature is original. The endotoxin had no obvious influence upon the renal Na excretion for 3 h post-injection, and did not affect plasma renin activity (PRA). After dexamethasone pre-treatment (0.02 mg kg-1, i.v. 75 min prior to endotoxin) the endotoxin-induced rise in rectal temperature initially was less steep and no biphasic pattern of the fever was observed. The PC and antidiuretic responses became delayed for about 2 h and were then much attenuated. Endotoxin-induced rise in PA was no longer observed, and a conspicuous natriuresis developed within 90 min post-endotoxin. It is concluded that endotoxin at the dose used causes liberation of ACTH to such an extent that adrenocortical hypersecretion not only of glucocorticoids, but also of aldosterone occurs. The observed differences in Na excretion suggest that this aldosterone hypersecretion may be of pathophysiological importance as a protection against inappropriate renal waste of Na during the early phase of endotoxin-induced fever.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Systemic and centrally mediated angiotensin II effects in the horse.

The primary aim of the study was to evaluate the potential value of intravenous (i.v.) infusion of angiotensin II (AII) for phonocardiographic differential diagnosis of equine valvular insufficiency. Ten-minute AII infusions at 4.5-33 pmol kg-1 min-1 induced clear-cut dose-dependent rises in systemic arterial blood pressure (aBP), whereas the pulmonary aBP remained largely unaffected. It implies that i.v. infusion of AII at about 10 pmol kg-1 min-1 could be a valuable tool for the acoustic differentiation between mitral and tricuspid valvular dysfunction in the horse. The infusion at, and above 9 pmol kg-1 min-1 caused increased heart rate. This chronotrophic effect was not strictly dose-dependent and exhibited significant tachyphylaxis. Angiotensin II administration at, or above 9 pmol kg-1 min-1 was needed to induce an urge to drink, suggesting that angiotensin-induced thirst does not appear in the euhydrated horse until the octapeptide reaches supraphysiological blood concentration. Determinations of plasma aldosterone concentration (PA) revealed comparatively high morning control values (269 +/- 46 pmol-1). Three consecutive AII infusions with 10-min intervals and at increasing dosages caused a cumulative, almost fourfold elevation of PA. The PA pattern indicated that AII-induced hypersecretion of aldosterone continued for several minutes after the end of the infusions, but also showed that the metabolic clearance of the hormone took precedency of the secretion within 20 min post-infusion. In two of the horses a fall in PA occurred during a fourth, final infusion, indicating that in these instances the previous AII administration had impoverished the store of aldosterone available for release from the adrenal cortex.

Aldosterone↗
PubMed1987

Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon.

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro. This contrasted with IFN-alpha which was inactive. In one case of AML (M2), partially purified IFN-gamma given intravenously caused a shift of the WBC profile from immature blasts to maturing myeloid cells and neutrophil granulocytes. Intravenous IFN-gamma treatment of another patient who had AML as a second malignancy resulted in a complete hematologic remission, normalization of marrow granulocyte-macrophage colony-forming cell in vitro growth, and conversion of marrow cytogenetics from 95% hyperdiploid clone with complex abnormalities into 100% diploid. The results indicate a potential use of IFN-gamma in the treatment of selected patients with AML and the possibility of in vitro pretreatment evaluation of these patients' leukemic response to IFNs.

Adult↗
PubMed1987

Dietary treatment of obesity localized in different regions. The effect of dietary fibre on relapse.

Ninety-four obese women were matched in pairs with similar body mass index and age but with as wide variations as possible in regional obesity, estimated by the waist/hip (W/H) circumference ratio. Body composition and metabolic variables were determined. The women were instructed to lower their energy intake to 1100 kcal/d, and were then seen every 4th week by a dietitian. After 5 per cent weight decrease initial measurements of body composition were repeated and when reaching weight steady state (less than 2 kg weight decrease upon two visits) both body composition and metabolic variables were again determined. Before the start of diet there was a positive correlation between W/H ratio on the one hand and insulin and alanine aminotransferase on the other. There was no correlation between rate of weight decrease, loss of cell body mass or diminution of circumferences with the W/H ratio. The examination of potential effects of dietary fibre on relapse is currently in progress.

Body Composition↗
PubMed1986

The topology of a membrane protein: the orientation of the 32 kd Qb-binding chloroplast thylakoid membrane protein.

Exposed portions of the 32 kd chloroplast membrane quinone-binding and triazine herbicide-binding protein of photosystem II have been mapped to the lumenal or to the outer (stromal) surface of the thylakoid by following reactions of antibodies generated against synthetic peptides corresponding to predicted hydrophilic amino acid sequences with normally oriented or everted membrane vesicles. These data have led to the construction of a model with five membrane-spanning domains. The model has been verified, in part, by immunoblots of fragments of the protein produced by trypsin treatment of thylakoids with peptide-specific antibodies. Some of the hydrophilic loops appear to be in close contact with proteins of the oxygen evolving complex of photosystem II inasmuch as their removal increases the antibody reaction.

Chloroplasts↗
PubMed1986

Isolation and characterization of the 10-kDa and 22-kDa polypeptides of higher plant photosystem 2.

Two polypeptides of 10 kDa and 22 kDa, shown to be components of the higher plant photosystem 2, were purified and examined. A NaCl/Triton X-100 treatment was designed, which released these two polypeptides from the thylakoid membrane, in concert with the extrinsic 16-kDa and 23-kDa proteins, concomitant with a loss in oxygen-evolution activity. After this treatment the oxygen-evolving activity of the photosystem 2 membranes devoid of the 10-kDa and the 22-kDa polypeptides could be restored with CaCl2, but not by readdition of the purified 23-kDa protein. This deficiency was caused by an inability of the 23-kDa protein to rebind to the photosystem 2 membranes. In analogy, the oxygen-evolution activity of a highly purified photosystem 2 core preparation, devoid of the 10-kDa and 22-kDa polypeptides, was stimulated by CaCl2, but not by the 23-kDa protein. We, therefore, suggest that the 10-kDa or the 22-kDa polypeptides provide a binding-site for the extrinsic 23-kDa protein to the thylakoid membrane. The 10-kDa and 22-kDa polypeptides were isolated through ion-exchange chromatography in the presence of detergents. They both displayed hydrophobic properties, verified by their low proportion of polar amino acid residues and their partition to the hydrophobic phase during Triton X-114 fractionation. The purified polypeptides did not contain metallic cofactors or substances with absorption in the visible region of the spectrum.

Amino Acids↗
PubMed1986

Stereoselective inhibition of prolactin secretion by (-)-HW-165, a novel 3-PPP congener; further support for similarities between central DA autoreceptors and pituitary lactotroph DA receptors.

The novel atypical dopamine (DA) receptor agonist HW-165 (trans-7-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinoline), a 'rigid' 3-PPP congener, and its enantiomers were investigated with regard to their actions on prolactin (PRL) release in rats. Racemic HW-165 dose dependently inhibited the elevation of PRL secretion induced by monoamine synthesis disruption (NSD 1015) combined either with abolished DA nerve impulse flow (GBL) or with monoamine depletion (reserpine). Racemic HW-165 was roughly equipotent to 3-PPP but 5-10-fold less potent than apomorphine. The PRL inhibitory action of racemic HW-165 was stereoselectively prevented by the DA antagonist (+)-butaclamol. Since the chiral aspect of lactotroph DA receptor activation by 'atypical' DA receptor agonists has not been covered in previous investigations the effects of the HW-165 enantiomers were now studied. Our findings suggest that the PRL inhibitory properties of racemic HW-165 reside in its (-) enantiomer, (+)-HW-165 being devoid of activity. Taken together, the results reinforce the concept that the pituitary lactotroph DA receptors mediating the inhibition of PRL release are similar, notably also from a stereochemical point of view, to central DA receptor sites with presumed high agonist sensitivity, such as DA autoreceptors.

4-Butyrolactone↗
PubMed1986

Central dopaminergic properties of HW-165 and its enantiomers; trans-octahydrobenzo(f)quinoline congeners of 3-PPP.

In the further development of CNS dopamine autoreceptor active compounds related to 3-PPP, the transfused 7-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinoline HW-165 and its enantiomers were synthesised. This paper describes the basic pharmacological properties of these latter, novel "atypical" dopaminergic agents, based on an extensive series of biochemical and behavioural experiments in rats. By and large, the pharmacological activities of HW-165 - essentially, if not exclusively, residing in its (4aS,10bS)-(-)-enantiomer - were similar to those displayed by (S)-(-)-3-PPP, indicating the simultaneous presence of central dopamine (autoreceptor) agonist and weak (postsynaptic) antagonist properties in the molecule. Thus, in non-pretreated animals HW-165 and its active species monotonically suppressed the spontaneous locomotion without causing catalepsy or other appreciable motor disabilities, and at the same time selectively reduced the dopamine synthesis, release/turnover and utilisation. Some differences in these biochemical responses to HW-165 [racemate or (-)-enantiomer] were, however, noted in the limbic vs. striatal brain areas (e.g. decrease of dopamine synthesis particularly in the limbic parts). On the other hand, while failing to reverse reserpine-induced akinesia or to elicit stereotyped behaviour, the agents markedly inhibited the dopamine synthesis in either of the dopamine-dominated cerebral regions in the reserpinised as well as in gamma-butyrolactone (GBL)-treated rats. As shown for racemic HW-165 after reserpine pretreatment, the inhibition of dopamine synthesis was completely and stereoselectively blocked by (+)-butaclamol, thereby supporting direct dopamine receptor interaction. Racemic HW-165 readily antagonised the d-amphetamine-induced locomotor hyperactivity. Apomorphine-induced hyperactivity was, however, distinctly more resistant to antagonism by HW-165 [racemate or (-)-enantiomer]. Moreover, the latter agents fully prevented the apomorphine-induced inhibition of striatal dopamine synthesis in otherwise non-pretreated rats, while only partly counteracting this effect of apomorphine in the limbic regions of such animals, and in either brain area of rats treated with gamma-butyro-lactone. The findings are interpreted within the context of the mixed dopamine agonist/antagonist properties (referred above) of HW-165 and its active (-)-species in relation to the adaptive state of central dopamine receptors and possible regional variations in feedback strength and organisation.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Butyrolactone↗
PubMed1986

(+)-UH 232 and (+)-UH 242: novel stereoselective dopamine receptor antagonists with preferential action on autoreceptors.

The (+)- and (-)-enantiomers of the 2-aminotetralin derivatives cis-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232) and cis-5-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (UH 242), were pharmacologically evaluated in rats in an extensive series of in vivo biochemical and behavioral experiments. These studies showed that the (+)- and (-)-enantiomers have differential effects on central dopamine (DA) receptors. Thus, (-)-UH 242 is a DA-receptor agonist stimulating both pre- and postsynaptic receptors. (-)-UH 232 is also active as a DA receptor agonist, although with much lower potency than (-)-UH 242. In contrast, (+)-UH 242 and (+)-UH 232 are characterized as DA receptor antagonists. Both (+) forms markedly accelerated DA synthesis and turnover and reversed the biochemical and behavioral effects of apomorphine. Locomotor activity was stimulated by the (+)-enantiomers over a wide dose range; hypomotility was induced only by high doses. The pharmacological profile of the (+)-enantiomers clearly differs from that of classical neuroleptics and suggests a preferential antagonistic action on DA autoreceptors. (+)-UH 232 and (+)-UH 242 may prove useful as experimental tools and as potential therapeutic agents (selectively increasing DA-ergic neurotransmission), e.g. in geriatric practice.

4-Butyrolactone↗
PubMed1986

Simultaneous expression of multiple immune complex receptors on murine thymocytes and spleen cells.

Mixed rosette studies were performed to evaluate the coexpression of IgG Fc. IgM Fc, and complement receptors (C3R) by thymocytes obtained from mice 7 days after cortisone injection and by spleen cells. Indicator cells coated with IgM, IgG, or C3 independently were mixed and could be distinguished by morphology or by a fluorescein label. In double-marker studies, 36% of spleen cells formed rosettes with IgG- and/or IgM-sensitized red blood cells. Among this population there was a 24% overlap of cells binding IgM and IgG complexes simultaneously. Of the spleen cells, 78% bound IgM- and/or C3-sensitized cells. Of the spleen cells forming rosettes with IgM and C3 indicator cells, 15% coexpressed these receptors. With IgG and C3 indicator cells, 58% of spleen cells bound to one or both kinds of complexes with an 18% overlap. Of cortisone-resistant thymocytes, 14% formed rosettes with IgM- and/or IgG-sensitized red blood cells; within this population there was an overlap of 21%. With IgM- or C3-sensitized cells, 19% of cortisone-resistant thymocytes bound to one or both, among which there was a coexpression of 21%. With IgG- or C3-sensitized cells, there was a 14% overlap of rosette-forming cells binding both. In triple-marker studies 79% of spleen cells formed rosettes with C3-, IgG-, and/or IgM-sensitized indicator cells, out of which 11% coexpressed IgM and IgG FcR, 20% coexpressed IgG and C3R, and 10% coexpressed IgM FcR and C3R. Of rosette-forming cells, 13% coexpressed all three receptors. With cortisone-resistant thymocytes, 19% bound one or more kinds of immune complexes. Among these, 9% coexpressed IgG FcR and C3R, 14% coexpressed IgM FcR and C3R, and 14% bound IgG and IgM complexes. We could not detect the simultaneous expression of all three receptors on cortisone-resistant thymocytes. Using Isopaque-Ficoll fractionation of cells binding C3-sensitized cells, cortisone-resistant thymocytes were enriched and depleted of C3-receptor-bearing cells and their Lyt phenotypes were determined by immunofluorescence microscopy. The C3-receptor-enriched population contained 56% C3R+ cells which were 79% Lyt-1 positive and 100% Lyt-2 positive. The C3R-depleted population contained 1.3% C3R+ cells with 10% Lyt-1 positive and 22% Lyt-2 positive among the total. Surface phenotypic expression of normal and cortisone-resistant thymocytes was also evaluated by direct and indirect fluorescence by fluorescence-activated cell sorter (FACS).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Inhibition of attachment of Streptococcus pneumoniae and Haemophilus influenzae by human milk and receptor oligosaccharides.

Human milk inhibited the attachment of Streptococcus pneumoniae and Haemophilus influenzae to human pharyngeal or buccal epithelial cells. Infant formulas and cow and buffalo milk showed a lower inhibitory activity against pneumococci and enhanced the adhesion of H. influenzae. The antiadhesive effect against S. pneumoniae was found in both the high- and the low-molecular-weight fractions of milk. The inhibitory activity in the high-molecular-weight fraction was independent of specific antibody content; it was present after immunoadsorption and in the milk from IgA-deficient women. The inhibitory activity in the low-molecular-weight fraction was in part explained by the content of oligosaccharides corresponding to the carbohydrate moieties of the neolactoseries of glycolipids, which have previously been shown to act as receptors for attaching pneumococci. The antiadhesive activity against H. influenzae was restricted to the high-molecular-weight fraction of the milk and was unaffected by immunoadsorption. Milk may protect against otitis by reducing colonization.

Adhesiveness↗