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Biomedical subjects

B Svensson

Publications and source records attributed to B Svensson.

At least 19 recordsLinked to original sources
PubMed2006

Sex: a major predictor of remission in early rheumatoid arthritis?

BACKGROUND: The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis. METHODS: 698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis. RESULTS: After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids. CONCLUSIONS: Early remission of rheumatoid arthritis by 28-joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.

Age of Onset↗
PubMed2006

Viscoelastic and histologic properties in scarred rabbit vocal folds after mesenchymal stem cell injection.

OBJECTIVE/HYPOTHESIS: The aim of this study was to analyze the short-term viscoelastic and histologic properties of scarred rabbit vocal folds after injection of human mesenchymal stem cells (MSC) as well as the degree of MSC survival. Because MSCs are antiinflammatory and regenerate mesenchymal tissues, can MSC injection reduce vocal fold scarring after injury? STUDY DESIGN: Twelve vocal folds from 10 New Zealand rabbits were scarred by a localized resection and injected with human MSC or saline. Eight vocal folds were left as controls. MATERIAL AND METHODS: After 4 weeks, 10 larynges were stained for histology and evaluation of the lamina propria thickness. Collagen type I content was analyzed from six rabbits. MSC survival was analyzed by fluorescent in situ hybridization staining from three rabbits. Viscoelasticity for 10 vocal folds was analyzed in a parallel-plate rheometer. RESULTS: The rheometry on fresh-frozen samples showed decreased dynamic viscosity and lower elastic modulus (P<.01) in the scarred samples injected with MSC as compared with the untreated scarred group. Normal controls had lower dynamic viscosity and elastic modulus as compared with the scarred untreated and treated vocal folds (P<.01). Histologic analysis showed a higher content of collagen type 1 in the scarred samples as compared with the normal vocal folds and with the scarred folds treated with MSC. MSCs remained in all samples analyzed. CONCLUSIONS: The treated scarred vocal folds showed persistent MSC. Injection of scarred rabbit vocal folds with MSC rendered improved viscoelastic parameters and less signs of scarring expressed as collagen content in comparison to the untreated scarred vocal folds.

Animals↗
PubMed2006

Effect of different premilking manual teat-cleaning methods on bacterial spores in milk.

Different teat-cleaning methods were evaluated to determine their effect on the presence of spores from anaerobic bacterial spore-formers in the milk. Artificial contamination was used to achieve uniform contamination of teats to reduce the number of cows and samples needed in the experiments and still obtain adequate power to detect differences among tested methods. Teats were contaminated experimentally with a large amount of Clostridium tyrobutyricum spores in a manure-water slurry. Various types of dry and moistened towels and different combinations of methods using soap or 2 types of towels, together with cleaning times of 10 or 20 s, were compared in 2 Latin square-designed experiments with 7 cows, 7 treatments, and 4 replications in each experiment. In comparison with control (no cleaning and no forestripping), cleaning teats with dry paper towels for 10 s reduced concentration of spores in milk by 45 to 50%. A 50 to 74% reduction was achieved using different types of moist towels for 10 s. Methods using 2 towels, soap, or a longer cleaning time reduced bacterial contamination by 85 to 91%. The most effective methods in reducing milk spore content (96% reduction) were use of a moist washable towel with or without soap followed by drying with a dry paper towel, for a total time of 20 s per cow. One of the best cleaning methods was studied in an additional experiment to determine the effect of different teat contamination mixtures. The Latin square-designed experiment with 8 cows, 8 treatments, and 2 replications showed that cleaning was independent of the tested contamination matrix (manure, soil, or sawdust), type of spores (Cl. tyrobutyricum and Bacillus cereus), or degree of contamination (manure or extra manure).

2-Propanol↗
PubMed2004

Aspects of the barley seed proteome during development and germination.

Analysis of the water-soluble barley seed proteome has led to the identification of proteins by MS in the major spots on two-dimensional gels covering the pI ranges 4-7 and 6-11. This provides the basis for in-depth studies of proteome changes during seed development and germination, tissue-specific proteomes, cultivar differences related to quality parameters, analysis of the genetic basis for spot variations and targeted investigations of specific proteins.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2004

Temporomandibular joint discectomy for treatment of unilateral internal derangements--a 5 year follow-up evaluation.

Fifteen fully dentated patients with pain and functional impairment due to unilateral temporomandibular joint disc displacements, who had undergone unsuccessful nonsurgical treatment, were treated with discectomies without any disc substitutes and followed for 5 years. Their contralateral temporomandibular joints were without any clinical or radiographic evidence of pathology. Functional pain was reduced and mandible opening ability increased although a full range of motion was not restored. This study verified that discectomies can reduce pain on chewing, however, pain at rest was not significantly changed. At 5 years 87% of the patients fulfilled the criteria for a successful result of TMJ surgery.

Adolescent↗
PubMed2004

Magnetic resonance imaging of the knee: a tool for prediction of joint damage in early rheumatoid arthritis?

OBJECTIVE: To evaluate the usefulness of magnetic resonance imaging (MRI) in predicting destructive rheumatoid arthritis (RA) in the knee joint, and to compare this method with clinical examination and conventional radiography (CR). METHODS: Clinical evaluations of the knee joint, followed by MRI and CR examinations were performed in 30 patients with early RA. The MRI examination included evaluation of inflammation using a synovitis score and evaluation of destruction with an erosion score. The first examinations were performed within 14 months from disease onset. Twenty-eight patients were re-examined after 1 year, and 23 patients after 3 years. 'Disease activity score' (DAS), using a 28 joints score (DAS28); health assessment questionnaire (HAQ); rheumatoid factor (RF); and C-reactive protein (CRP) were also analysed. RESULTS: At baseline, MRI found synovitis in 29 patients, of whom 18 also had clinical synovitis. At baseline five patients had 17 MRI erosions, whereas on CR two patients had one erosion each. After 1 year 17 of 35 and after 3 years 28 of 55 MRI erosions were detected also on CR. In only one case CR showed an erosion that was not visible on MRI. The MRI synovitis score (reflecting the extent of the synovitis) at baseline correlated significantly with the number of erosions on MRI both at year 1 and 3, and with the number of erosions on CR at 3 years. In logistic multiple regression analyses the MRI-synovitis score proved to be the best independent predictor of erosiveness. CONCLUSION: MRI was superior to clinical examination and CR in detecting erosions. MRI synovitis score was the best independent predictor of erosiveness in the knee joint in patients with early RA.

Adult↗
PubMed2004

Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP).

OBJECTIVE: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. METHODS: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. RESULTS: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. CONCLUSIONS: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.

Adult↗
PubMed2003

Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia.

Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes. Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postprandial hyperlipemia. In the present double-blind, placebo-controlled parallel study, 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L(-1 )and serum cholesterol >5.3 mmol L-1 at the end of a 3-month dietary run-in period were treated with atorvastatin at 10 mg day-1 for at least 10 weeks. During the last 5 weeks the patients were randomized into two groups receiving 1.68 g day(-1) omega-3 fatty acids (omega-3 FA) or placebo (corn oil). The fasting levels of FVII antigen (FVII-Ag) and FVII coagulant activity (FVII:C) were high compared with healthy males. The fasting levels of activated FVII (FVIIa) and FVII-Ag correlated both to serum triglycerides and apolipoprotein A1 (apoA1). FVIIa and FVII:C increased during postprandial hyperlipemia. This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels, but not to the degree of postprandial hypertriglyceridemia. The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo. This treatment also reduced the postprandial level of FVIIa. omega-3 FA in addition to atorvastatin further reduced FVIIa concentrations, fasting and postprandially, and also significantly reduced FVII:C and FVII-Ag during postprandial hyperlipemia. Prothrombin fragment 1 + 2 (F1 + 2) increased during postprandial hyperlipemia. This increase was significantly reduced after treatment with atorvastatin plus omega-3 FA. The increase of F1 + 2 measured as incremental area under the curve (iAUC) during postprandial hyperlipemia correlated to the fasting levels of FVIIa, FVII:C and FVII-Ag and also to the levels of these factors during postprandial lipemia. In conclusion, patients with combined hyperlipemia are at risk for activation of the coagulation system, particularly during postprandial lipemia. This activation may be significantly reduced by statins and omega-3 FA.

Adult↗
PubMed2003

Magnetic resonance imaging of the fifth metatarsophalangeal joint compared with conventional radiography in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate if magnetic resonance imaging (MRI) is superior to conventional radiography for detection of erosions in the fifth metatarsophalangeal (MTP5) joint. METHODS: Within one year from the onset of rheumatoid arthritis (RA) (baseline), one and three years thereafter MRI and conventional radiographs of the MTP5 joint were performed in 23 patients. RESULTS: MRI revealed erosions in 10 patients at baseline, in 15 after one year and in 15 patients after 3 years. On conventional radiography, there were erosions in 10 patients at baseline, 16 after one year as well as after 3 years. The agreement between the two imaging methods was fair to good at baseline and after one and three years (kappa 0,65, 0,51 and 0,51 respectively). The number of patients with clinical evidence of synovitis decreased considerably over time although the number of patients with MRI-synovitis was unchanged and the number of patients with erosions increased. CONCLUSIONS: MRI was not superior to conventional radiography in detecting erosions in MTP5 joints in patients with early RA. Most erosions developed during the first year of observation. Synovitis on MRI may be a marker of future development of erosions in the MTP5 joint.

Adult↗
PubMed2001

Modulation of the multisubstrate specificity of Thermus maltogenic amylase by truncation of the N-terminal domain and by a salt-induced shift of the monomer/dimer equilibrium.

The relation between the quaternary structure and the substrate specificity of Thermus maltogenic amylase (ThMA) has been investigated. Sedimentation diffusion equilibrium ultracentrifugation and gel filtration analyses, in combination with the crystal structure determined recently, have demonstrated that ThMA existed in a monomer/dimer equilibrium. The truncation of ThMA by removing the N-terminal domain, which is composed of 124 amino acid residues, resulted in the complete monomerization of the enzyme (ThMADelta124) accompanied by a drastic decrease in the activity for beta-cyclodextrin (beta-CD) and a relatively smaller reduction of the activity for starch. Despite the overall low activity of ThMADelta124, the activity was higher toward starch than beta-CD, and the ratio of the specific activities toward these substrates was approximately 100 fold higher than that of wild-type ThMA. Furthermore, the addition of KCl to wild-type ThMA shifted the monomer/dimer equilibrium toward the monomer. In the presence of 1.0 M KCl, the relative activity of ThMA toward beta-CD decreased to 74%, while that for soluble starch increased to 194% compared to the activities in the absence of KCl. Thus, the ThMA monomer and dimer are both inferred to be enzymatically active but with a somewhat different substrate preference. Kinetic parameters of the wild-type and truncated enzymes also are in accordance with the changes in their specific activities. We thus provide evidence in support of a model, which shows that the relative multisubstrate specificity of ThMA is influenced by the monomer/dimer equilibrium of the enzyme.

Amino Acid Sequence↗
PubMed2001

Both binding sites of the starch-binding domain of Aspergillus niger glucoamylase are essential for inducing a conformational change in amylose.

The interaction of the two binding sites of the starch-binding domain (SBD) of Aspergillus niger glucoamylase 1 (GA-I) with substrate has been investigated by using atomic force microscopy (AFM) and UV difference spectroscopy in combination with site-specific mutants of both SBD and GA-I. The SBD possesses two binding sites with distinct affinities towards the soluble linear substrate maltoheptaose; dissociation constants (K(d)) of 17 and 0.95 microM were obtained for W563 K (binding site 2 mutant) and W590 K (binding site 1 mutant), respectively, compared to an apparent K(d) of 23 microM for the wild-type SBD. Further, the two sites are almost but not totally independent of each other for binding, since abolishing one site does not prevent the amylose chain binding to the other site. Using AFM, we show that the amylose chains undergo a conformational change to form loops upon binding to the SBD, using either the recombinant wild-type SBD or a catalytically inactive mutant of GA-I. This characteristic conformation of amylose is lost when one of the SBD binding sites is eliminated by site-directed mutagenesis, as seen with the mutants W563 K or W590 K. Therefore, although each binding site is capable of simple binding to a ligand, both sites must be functional in order to induce a gross conformational change of the amylose molecules. Taken together these data suggest that for the complex with soluble amylose, SBD binds to a single amylose chain, site 1 being responsible for the initial recognition of the chain and site 2 being involved in tighter binding, leading to the circularisation of the amylose chain observed by AFM. Binding of the SBD to the amylose chain results in a novel two-turn helical amylose complex structure. The binding of parallel amylosic chains to the SBD may provide a basis for understanding the role of the SBD in facilitating enzymatic degradation of crystalline starches by glucoamylase 1.

Amino Acid Substitution↗
PubMed2001

Specificity modulation of barley alpha-amylase through biased random mutagenesis involving a conserved tripeptide in beta --> alpha loop 7 of the catalytic (beta/alpha)(8)-barrel domain.

The relative specificity and bond cleavage pattern of barley alpha-amylase 1 (AMY1) were dramatically changed by mutation in F(286)VD that connected beta-strand 7 of the catalytic (beta/alpha)(8)-barrel to a succeeding 3(10)-helix. This conserved tripeptide of the otherwise variable beta --> alpha segment 7 lacked direct ligand contact, but the nearby residues His290 and Asp291 participated in transition-state stabilization and catalysis. On the basis of sequences of glycoside hydrolase family 13, a biased random mutagenesis protocol was designed which encoded 174 putative F(286)VD variants of C95A-AMY1, chosen as the parent enzyme to avoid inactivating glutathionylation by the yeast host. The FVG, FGG, YVD, LLD, and FLE mutants showed 12-380 and 1.8-33% catalytic efficiency (k(cat)/K(m)) toward 2-chloro-4-nitrophenyl beta-D-maltoheptaoside and amylose DP17, respectively, and 0.5-50% activity for insoluble starch compared to that of C95A-AMY1. K(m) and k(cat) were decreased 2-9- and 1.3-83-fold, respectively, for the soluble substrates. The starch:oligosaccharide and amylose:oligosaccharide specificity ratios were 13-172 and 2.4-14 for mutants and 520 and 27 for C95A-AMY1, respectively. The FVG mutant released 4-nitrophenyl alpha-D-maltotrioside (PNPG(3)) from PNPG(5), whereas C95A-AMY1 produced PNPG and PNPG(2). The mutation thus favored interaction with the substrate aglycon part, while products from PNPG(6) reflected the fact that the mutation restored binding at subsite -6 which was lost in C95A-AMY1. The outcome of this combined irrational and rational protein engineering approach was evaluated considering structural accommodation of mutant side chains. FVG and FGG, present in the most active variants, represented novel sequences. This emphasized the worth of random mutagenesis and launched flexibility as a goal for beta --> alpha loop 7 engineering in family 13.

Amino Acid Sequence↗
PubMed2001

Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.

Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.

Amino Acid Sequence↗
PubMed2001

Synthesis of nitrogen analogues of salacinol and their evaluation as glycosidase inhibitors.

The syntheses of two nitrogen analogues (11 and 12) of the naturally occurring sulfonium ion, salacinol (7) are described. The latter compound is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of a 1,4-dideoxy-1,4-imino-D- or L-arabinitol at the least hindered carbon of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The nitrogen analogues bear a permanent positive charge and serve as mimics of the sulfonium ion. We reasoned that these ammonium derivatives should function in a manner similar to that of known glycosidase inhibitors of the alkaloid class such as castanospermine (4) and deoxynojirimycin (5). Enzyme inhibition assays indicate that salacinol (7) is a weak (K(i) = 1.7 mM) inhibitor of glucoamylase, whereas compounds 11 and 12 inhibit glucoamylase with K(i) values in the range approximately 10-fold higher. The nitrogen analogues 11 and 12 showed no significant inhibitory effect of either barley alpha-amylase (AMY1) or porcine pancreatic alpha-amylase (PPA) at concentrations of 5 mM. In contrast, salacinol (7) inhibited AMY1 and PPA in the micromolar range, with K(i) values of 15 +/- 1 and 10 +/- 2 microM, respectively.

Amylases↗
PubMed2001

[Unbroken continuity of patient care in shoulder pain. Same initial care in primary health services as in hospitals].

Thirty percent of all patients that consult their primary care physicians for pain in their musculoskeletal systems have pain in the neck/shoulder region, while 23% have lower back pain. Of major concern in Sweden is a patient's lengthy waiting period before seeing a specialist, with a resultant delay in treatment. A multidisciplinary group of physicians and physical therapists has therefore been working on and refining a system of tools to provide an "unbroken chain of care" for the diagnosis and treatment of patients with shoulder pathology. An unbroken chain of care enables the clinician regardless of specialty to provide the highest level of care to all patients with the same initial diagnostic and treatment parameters. Axelina is the tool that provides all the standardized treatment algorithms, rehabilitation plans and detailed home exercises. Axelina also contains a two-day instructional package with case studies presented on video.

Continuity of Patient Care↗
PubMed2001

Relationship of sequence and structure to specificity in the alpha-amylase family of enzymes.

The hydrolases and transferases that constitute the alpha-amylase family are multidomain proteins, but each has a catalytic domain in the form of a (beta/alpha)(8)-barrel, with the active site being at the C-terminal end of the barrel beta-strands. Although the enzymes are believed to share the same catalytic acids and a common mechanism of action, they have been assigned to three separate families - 13, 70 and 77 - in the classification scheme for glycoside hydrolases and transferases that is based on amino acid sequence similarities. Each enzyme has one glutamic acid and two aspartic acid residues necessary for activity, while most enzymes of the family also contain two histidine residues critical for transition state stabilisation. These five residues occur in four short sequences conserved throughout the family, and within such sequences some key amino acid residues are related to enzyme specificity. A table is given showing motifs distinctive for each specificity as extracted from 316 sequences, which should aid in identifying the enzyme from primary structure information. Where appropriate, existing problems with identification of some enzymes of the family are pointed out. For enzymes of known three-dimensional structure, action is discussed in terms of molecular architecture. The sequence-specificity and structure-specificity relationships described may provide useful pointers for rational protein engineering.

Amino Acid Sequence↗
PubMed2001

Extensive N-glycosylation reduces the thermal stability of a recombinant alkalophilic bacillus alpha-amylase produced in Pichia pastoris.

Alkalophilic Bacillus alpha-amylase (ABA) was produced in the yeast Pichia pastoris with a yield of 50 mg L(-1) of culture supernatant. The recombinant protein, rABA, was glycosylated at seven of the nine sites for potential N-glycosylation as identified by automated peptide sequencing and MALDI-TOF MS of tryptic fragments. The number of hexose units within each glycan chain was found to vary from 8 to 18 as calculated from the masses of glycosylated peptide fragments. Temperature stability measurements in the absence of substrate showed that the T(50) of glycosylated rABA and its endoglycosidase H-deglycosylated form was 76 degrees C while that of ABA purified from Bacillus was 89 degrees C thus demonstrating that the original temperature stability of ABA was not retained by rABA. The relative thermoperformance, i.e., the activity at 80 degrees C relative to that at 37 degrees C was 0.9 +/- 0.3 for rABA. Removal of all seven N-linked glycans by endoglycosidase H increased the relative thermoperformance to 2.4 +/- 0.6, compared to the value of 3.5 +/- 1.1 for ABA. Thus, removal of the N-linked glycans did not improve the thermostability of rABA but modified its thermoperformance to approach that of the original Bacillus enzyme. rABA had the highest activity around pH 6. Treatment of rABA with endoglycosidase H shifted the pH activity profile in a more alkaline direction approaching the pH activity profile of ABA.

Amino Acid Sequence↗