Search PubMed⌕ Search

Biomedical subjects

B Svensson

Publications and source records attributed to B Svensson.

At least 217 records · Page 12Linked to original sources

(R)- and (S)-5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten- 8-ylamine. Stereoselective interactions with 5-HT1A receptors in the brain.

The enantiomers of 5,6,7,8-tetrahydro-1-hydroxy-N,N-dipropyl-9H-benzocyclohepten-8-++ +ylamine (3) have been synthesized and evaluated for central 5-hydroxytryptamine (5-HT) and dopamine (DA) receptor activity by use of behavioral and biochemical tests in rats. In addition, the ability of the compounds to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The absolute configuration of the enantiomers of 3 was determined indirectly by X-ray diffraction of (+)-(8R,alpha R)-5,6,7,8-tetrahydro-1-methoxy-N-(alpha-phenethyl)-9H- benzocyclohepten-8-ylamine hydrochloride (9.HCl), a resolved synthetic precursor. The stereoselectivity of the interaction of 3 with 5-HT1A receptors was more pronounced than that of 8-hydroxy-2-(dipropylamino)tetralin (1; 8-OH-DPAT); only (R)-3 displayed 5-HT activity. However, (R)-3 was of lower potency than any of the enantiomers of 1. The enantiomer (S)-3, which was found to be inactive as a 5-HT-receptor agonist, appeared to be a weakly potent DA-receptor agonist whereas (R)-3 seemed to be devoid of dopaminergic activity. The conformational preferences of 3 were studied by use of NMR spectroscopy and molecular mechanics calculations. Preferred conformations of (R)-3 are similar in shape to those of the stereoselective 5-HT1A-receptor agonist (2R,3S)-8-hydroxy-3-methyl-2-(dipropylamino)tetralin.

Animals↗

Site-directed mutagenesis at the active site Trp120 of Aspergillus awamori glucoamylase.

Trp120 of Aspergillus awamori glucoamylase has previously been shown by chemical modification to be essential for activity and tentatively to be located near subsite 4 of the active site. To further test its role, restriction sites were inserted in the cloned A.awamori gene around the Trp120 coding region, and cassette mutagenesis was used to replace it with His, Leu, Phe and Tyr. All four mutants displayed 2% or less of the maximal activity (kcat) of wild-type glucoamylase towards maltose and maltoheptaose. Michaelis constants (KM) of mutants decreased 2- to 3-fold for maltose and were essentially unchanged for maltoheptaose compared with the wild type, except for a greater than 3-fold decrease for maltoheptaose with the Trp120----Tyr mutant. This mutant also bound isomaltose more strongly and had more selectivity for its hydrolysis than wild-type glucoamylase. A subsite map generated from malto-oligosaccharide substrates having 2-7 D-glucosyl residues indicated that subsites 1 and 2 had greater affinity for D-glucosyl residues in the Trp120----Tyr mutant than in wild-type glucoamylase. These results suggest that Trp120 from a distant subsite is crucial for the stabilization of the transition-state complex in subsites 1 and 2.

Amino Acid Sequence↗

Podophyllum derivatives (CPH 82) compared with placebo in the treatment of rheumatoid arthritis.

The efficacy, tolerance, and safety of CPH 82 (semisynthetic lignan glycosides) (Conpharm AB) for patients with rheumatoid arthritis (RA) were assessed in a 12-week double-blind placebo-controlled study. Thirteen patients out of 15 in the CPH 82 group and 10 out of 15 in the placebo group completed the study. No improvement was seen in placebo treated patients. Patients treated with CPH 82 showed a statistically significant improvement in most clinical and immunological variables. Some patients treated with CPH 82 reported gastrointestinal discomfort (diarrhoea and abdominal pain).

Arthritis, Rheumatoid↗

Regional distant sequence homology between amylases, alpha-glucosidases and transglucanosylases.

Amylases possess short, conserved regions near functional side chains. Sequence comparison extends this relationship to comprise a maltase and a cyclodextrin glucanotransferase. Similarity also exists with intestinal sucrase-isomaltase and fungal glucoamylase near identified essential carboxyl groups. Homology between COOH-terminal regions of glucoamylase and cyclodextrin glucanotranserase may indicate raw-starch binding areas. It is suggested that amylases, alpha-glucosidases, and transglucanosylases acting on 1,4- and 1,6-alpha-glucosidic linkages share key structural features in the active centres.

1,4-alpha-Glucan Branching Enzyme↗

Functional assessment of early rheumatoid arthritis.

A new performance index, SOFI (Signals of Functional Impairment), is described. This aims to detect functional impairment of different joints as early as possible. It comprises assessments of hand, arm and leg function. The assessment time is short and reliability is satisfactory. The index correlates significantly with range of motion, Ritchie index, grip strength, and the Stanford Health Assessment Questionnaire (HAQ) disability index. The last mentioned was used in parallel with the new index to study 50 early RA patients. These were followed every 3-6 months for 1 year. Both indices seemed to fluctuate with changes in the patient's state.

Adult↗

Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis.

Genomic DNA from 17 Swedish patients with familial amyloidotic polyneuropathy (FAP), and 50 healthy controls were tested with a cDNA transthyretin probe. In seven of the patients, FAP was not reported in either of their parents. All 50 controls showed restriction fragments of 6.6 kb and 3.2 kb after cleavage with Nsil, while the 17 FAP patients showed RFLP markers of 5.1 and 1.5 kb. These observations indicate the same methionine for valine substitution at position 30 in Swedish patients with FAP as seen in patients with FAP from Japan, Portugal and FAP-patients of Swedish descent from USA. However, the mean onset of FAP symptoms for the 17 Swedish patients was found to be significantly later than for the patients from Japan, Portugal and USA.

Adult↗

Palmoplantar pustulosis and sternocostoclavicular arthro-osteitis.

Seventeen patients with shoulder pain and radiographic involvement of the sternoclavicular or sternocostal joints, or both, are described. Eleven of these patients also had palmoplantar pustulosis. Histological examination of the joints showed chronic and subacute inflammation, increased osteoblastic activity, and cartilage degeneration. Propionibacterium acnes was cultured in tissue samples from seven of the 15 biopsied patients, a finding at variance with those of previous reports. The possibility that sternoclavicular arthro-osteitis is of infectious origin should be the subject of further investigation. Non-steroidal anti-inflammatory drugs (NSAIDs) may provide pain relief, possibly owing to their inhibitory action on osteoblasts. In cases of severely restricted movement or severe pain resection of the medial clavicle may be considered.

Adult↗

Assessing disability in patients with rheumatoid arthritis. Use of a Swedish version of the Stanford Health Assessment Questionnaire.

The validity and reliability under Swedish conditions of a translated and slightly modified version of the Stanford Health Assessment Questionnaire (HAQ), referred to here as the ADL questionnaire, was studied. Sixty-four patients with definite/classical rheumatoid arthritis (RA) participated in the major part of the investigation. In addition, inter-observer reliability was studied in the testing of 15 other patients with RA. The questionnaire was filled in by the patients twice (ADL Tests 1 and 2) with a one-week interval between. A physiotherapist or occupational therapist also assessed each of the patients on a sample of ADL functions (ADL Test 3). Joint mobility, grip-strength, pain, Ritchie index and ESR were likewise checked. Results indicated inter-observer reliability to be high for the ADL (r(S) = 0.98), for joint mobility (r(S) = 0.86), and for the Ritchie index (r(S) = 0.83). The test-retest reliability for the ADL questionnaire which the patients filled in (Tests 1 and 2) was high r(S) = 0.91. Results of the ADL questionnaires the patients completed were found to correlate fairly closely with the observations of the therapists, r(S) = 0.71. The validity of the scoring system was found to be sufficient, using Ward's cluster analysis for comparing the original HAQ scores with scores on all the questions included in the questionnaire. Thus, the translated and somewhat modified version of the ADL questionnaire studied here appears to possess a high degree of reliability and validity in assessing patients with RA.

Activities of Daily Living↗

The occurrence of rheumatoid factor isotypes in early definite rheumatoid arthritis--no relationship with erosions or disease activity.

Seventy-one patients with definite rheumatoid arthritis and disease duration less than 2 years were followed prospectively. At study entry 43 patients had IgG rheumatoid factor (RF), 59, IgA-RF and 64, IgM-RF as measured with an ELISA; 48 were Waaler-Rose positive. After 2 years, joint erosions were present in 51 patients and absent in 19. One patient has not been followed long enough. The calculated relative risks contributed by different RF to the presence of erosions were low. No significant correlations between markers of disease activity and RF levels initially were found. The clinical value of RF isotype determination seems limited.

Aged↗

Crystallization of barley malt alpha-amylases and preliminary x-ray diffraction studies of the high pI isozyme, alpha-amylase 2.

alpha-Amylase isozymes 1 and 2 isolated from germinated barley seeds have been crystallized by the hanging- or sitting-drop vapor diffusion technique. Crystals of alpha-amylase 2 suitable for x-ray diffraction analysis were grown at pH 6.7 and 22 degrees C from a solution of 1 mM calcium chloride, 10 mM MES, and 16% saturated ammonium sulfate. The space group is trigonal P3121 (or P3221) with unit cell dimensions a = b = 135.20 A, c = 79.63 A, and probably two molecules per asymmetric unit.

Crystallization↗

Reduced turnover of the elongation factor EF-1 X ribosome complex after treatment with the protein synthesis inhibitor II from barley seeds.

The effect of the protein synthesis inhibitor II from barley seeds (Hordeum sp.) on protein synthesis was studied in rabbit reticulocyte lysates. Inhibitor treatment of the lysates resulted in a rapid decrease in amino acid incorporation and an accumulation of heavy polysomes, indicating an effect of the inhibitor on polypeptide chain elongation. The protein synthesis inhibition was due to a catalytic inactivation of the large ribosomal subunit with no effect on the small subparticle. The inhibitor-treated ribosomes were fully active in participating in the EF-1-dependent binding of [14C]phenylalanyl-tRNA to poly(U)-programmed ribosomes in the presence of GTP and the binding of radioactively labelled EF-2 in the presence of GuoPP[CH2]P. Furthermore, the ribosomes were still able to catalyse peptide-bond formation. However, the EF-1- and ribosome-dependent hydrolysis of GTP was reduced by more than 40% in the presence of inhibitor-treated ribosomes, while the EF-2- and ribosome-dependent GTPase remained unaffected. This suggests that the active domains involved in the two different GTPases are non-identical. Treatment of reticulocyte lysates with the barley inhibitor resulted in a marked shift of the steady-state distribution of the ribosomal phases during the elongation cycle as determined by the ribosomal content of elongation factors. Thus, the content of EF-1 increased from 0.38 mol/mol ribosome to 0.71 mol/mol ribosome, whereas the EF-2 content dropped from 0.20 mol/mol ribosome at steady state to 0.09 mol/mol ribosome after inhibitor treatment. The data suggest that the inhibitor reduces the turnover of ribosome-bound ternary EF-1 X GTP X aminoacyl-tRNA complexes during proof-reading and binding of the cognate aminoacyl-tRNA by inhibiting the EF-1-dependent GTPase.

Animals↗

Docosapolyenoic fatty acids and human endothelial cells.

The total fatty acids in human endothelial cells include approximately 5% each of 22:4(n-6), 22:5(n-3) and 22:6(n-3), whereas 22:5(n-6) is present only in trace amounts. This study evaluates the effect of three of these fatty acids bound to albumin on lipid composition and prostacyclin (prostaglandin I2) synthesis in primary cultures of endothelial cell monolayers. 22:4(n-6), 22:5(n-6) and 22:6(n-3) were all incorporated into total phospholipids. 20:4(n-6) was reduced in phospholipids in all cells incubated with the three different docosaenoic fatty acids. This reduction was abolished when equimolar concentrations of 20:4(n-6) and the separate docosaenoic fatty acid were added to the medium simultaneously. 22:4(n-6) incorporation into the free fatty acids was associated with an increase of 20:4(n-6) in this fraction. 22:4(n-6), 22:5(n-6) and 22:5(n-3) all reduced the synthesis of prostacyclin measured as 6-ketoprostaglandin F1 alpha. These effects were reversed by simultaneous incubation with 20:4(n-6). This study shows that three of the docosaenoic fatty acids present in human endothelial cells of the (n-6) and (n-3) family were all incorporated into endothelial cells with a simultaneous reduction in 20:4(n-6). The three fatty acids reduced the synthesis of prostacyclin.

6-Ketoprostaglandin F1 alpha↗

Characterization of a glucoamylase G2 from Aspergillus niger.

Peptide fragments were generated by enzymic or chemical degradation of the small form, G2, and the large form, G1, of Aspergillus niger glucoamylase (EC 3.1.2.3). The G2 form was either identical to residues Ala1-Pro512 or to Ala1-Ala514 of the G1 polypeptide chain containing 616 amino acid residues. Structural analysis of the O-linked carbohydrates from the 70-amino-acid-residues long extensively glycosylated segment of G2 revealed no significant differences in the contents of single mannose and oligosaccharide units in comparison to the corresponding region of G1. The results suggest that the present G2 form has been generated by limited proteolysis of the larger G1. In contradistinction to this, a recently reported splicing out of an intervening sequence from G1 mRNA leads to a smaller mRNA coding for a G2 protein product with a different COOH-terminal sequence than the G2 form described in the present work [Boel et al. (1984) EMBO J. 3, 1097-1102].

Amino Acid Sequence↗

Trichorhinophalangeal syndrome type I: symptoms and signs, radiology and genetics.

The present study shows the occurrence of the trichorhinophalangeal syndrome type I in a Swedish family. Five members were affected and they were examined clinically and radiologically, and four of them were also cytogenetically examined. Three of them had dysplasia of the hip joints reminiscent of the Legg-Calvé-Perthes disease. Functional hand problems were common. High resolution G banding displayed normal chromosome complements. The inheritance was autosomal dominant. The data presented stress the importance of identifying the syndrome early in life so as to prevent the development of impaired hand and hip function.

Abnormalities, Multiple↗