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Biomedical subjects

B Svensson

Publications and source records attributed to B Svensson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Costochondral grafts to replace mandibular condyles in juvenile chronic arthritis patients: long-term effects on facial growth.

Long-term facial growth and clinical outcome after replacement of arthritic mandibular condyles by costochondral grafts and postoperative orthodontic guidance of the occlusion were studied until completion of facial growth in patients (n = 12) with juvenile chronic arthritis (JCA) affecting their temporo-mandibular joints (TMJs). The patients were between 10.1 and 16.7 years of age at surgery. Clinical records and radiographs for cephalometric measurements were taken preoperatively, 6-8 weeks after surgery and after completion of facial growth. A considerable potential for growth of the costochondral graft/mandible unit was demonstrated in all patients. The results also indicated a considerable risk of asymmetrical mandibular overgrowth (n = 8), which could not be correctly assessed until after skeletal maturation was complete. Without any active orthodontic treatment, compensatory growth of the alveolar processes closed the lateral open bites, which were created during surgery. The functional results of the reconstructed temporo-mandibular joints were good and the morbidity rate was low. Costochondral grafting is a versatile treatment when the TMJs are severely affected by JCA, but requires supervision of patients until skeletal maturation, to monitor possible mandibular overgrowth. Advantages of this method were re-established mandibular growth, good mandibular function, a low morbidity rate and early aesthetic improvement.

Adolescent↗
PubMed1998

A RAPD-PCR method for large-scale typing of Bacillus cereus.

A robust RAPD-PCR procedure for large-scale typing of Bacillus cereus was developed. It is based on a simple DNA preparation, involving only freezing and boiling of cells in water with active carbon. By using a computerized system for data collection and processing, an efficient system for handling RAPD patterns for large-scale investigations was achieved. The procedure was highly discriminatory for Bacillus cereus strains and was found to give reproducible classification of RAPD fingerprints for five reference strains.

Animals↗
PubMed1998

Bone scan and serum markers of bone and cartilage in patients with knee pain and osteoarthritis.

OBJECTIVE: To study the relations between knee joint abnormalities, reflected by bone scintigraphy and serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP). DESIGN: In a group of 38 individuals aged 37-54 years with chronic knee pain for more than four years, both knees were investigated with bone scan. The bone scans were graded for the extent of abnormalities. Radiographs of both knees were graded for tibiofemoral and patellofemoral osteoarthritis (OA). Serum levels of COMP and BSP were measured by immunoassays. RESULTS: Bone scan abnormalities were detected in 26/38 individuals and radiographic OA in 23/38 individuals. The serum concentrations of COMP and BSP were significantly higher in the individuals with bone scan abnormalities (P = 0.02 and P = 0.004, respectively). In addition, the serum levels of COMP correlated positively with the extent of bone scan abnormalities (N = 38), r = 0.56, P = 0.002. Serum BSP did not correlate to the extent of scan abnormalities. CONCLUSIONS: In individuals with knee pain, serum levels of COMP and BSP differ between those with or without bone scan abnormalities in the knee joints. This suggests that measurements of the serum levels of these markers have potential as means for evaluation of tissue changes in individuals with long standing knee pain in relation to early stages of OA.

Adult↗
PubMed1998

Joint-space width in the axial view of the patello-femoral joint. Definitions and comparison with MR imaging.

PURPOSE: To validate a bony landmark on the dorsal aspect of the patella for measurement of the interbone distance in the axial radiogram of the patello-femoral joint (PFJ); to assess the reproducibility of this radiogram and the minimal joint-space (MJS) width measurements in the medial and lateral compartments of the PFJ in this view; and to relate the MJS of the PFJ to MR-detected cartilage defects in the same joint. MATERIAL AND METHODS: Fifty-seven individuals with chronic knee pain (aged 41-58 years, mean 50 years) were examined with an axial view of the PFJ in the standing position. The MJS was measured with a mm-graded ruler. On the same day, an MR examination was performed with proton density- and T2-weighted turbo spin-echo sequences on a 1.0 T imager. We noted the cartilage defects in the PFJ in axial and sagittal MR images, and the shape of the subchondral cortex of the medial and lateral articular surfaces of the patella in sagittal MR images. RESULTS AND CONCLUSION: The bony landmark was found on all articular surfaces. The axial view of the PFJ and the MJS measurements were reproducible. An MJS of <5 mm showed high specificity for MR-detected cartilage defects. Thus an MJS of 5 mm proved to be a limit in the diagnosis of joint-space narrowing in the PFJ in middle-aged individuals with chronic knee pain.

Adult↗
PubMed1998

CPH-82 (Reumacon) versus auranofin (Ridaura): a 36-week study of their respective onset of action rates in RA.

The onset of action rate of CPH-82 (Reumacon), was compared with that of auranofin (AUR; Ridaura) in a 36-week randomised, double-blind, multicentre study of 60 patients with rheumatoid arthritis (RA). As compared with respective baseline values, the CPH-82 group manifested significant improvement in grip strength, Ritchie's articular index (RAI), pain ratings, and HAQ (health assessment questionnaire) scores after 8, 12, 24, and 36 weeks of treatment, with the exception of the 24-week HAQ score. The AUR group manifested corresponding improvement in RAI after 8, 12, 24, and 36 weeks. Significant differences in changes from baseline values in favour of the CPH-82 group were found for grip strength at 12 and 24 weeks, RAI score at 8 weeks, VAS score at 8 and 12 weeks, and HAQ score at 8 weeks. The findings suggest CPH-82 to manifest a more rapid onset of action than AUR. The two drugs were similar in tolerance and safety.

Adult↗
PubMed1998

Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint.

Serum concentrations of two extracellular matrix molecules were determined over a 3 yr period in individuals with chronic knee pain to investigate whether sequential serum measurements of cartilage- and bone-derived molecular fragments reflect early stages of osteoarthritis (OA) of the knee joints. Thirty-eight individuals with chronic knee pain (> 3 months at inclusion) with or without radiographic evidence of knee joint OA at the 3 yr follow-up radiographic examination were studied. Serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) increased significantly (P < 0.001) in the 23 individuals with radiographic OA at follow-up, while remaining unchanged in the 15 individuals with normal radiographs at follow-up. The baseline concentrations of the two variables did not differ between the groups. These findings suggest that pathological processes in cartilage and subchondral bone coincide in OA, and appear to be reflected by circulating levels of macromolecules released from cartilage and bone. Changes in serum levels of COMP and BSP are potential tools in studies of knee joint OA in subjects with chronic knee pain.

Adult↗
PubMed1998

Epoetin beta in the treatment of anemia in patients with advanced gastrointestinal cancer.

PURPOSE: The possibility that epoetin beta (EPO) could increase hemoglobin (B-Hb) levels and improve quality of life (QoL) in patients with advanced gastrointestinal cancers was investigated. PATIENTS AND METHODS: One hundred patients with gastric, pancreatic, biliary, or colorectal cancers and subnormal B-Hb levels were included in a randomized study to test low-dose EPO (2,000 U subcutaneously thrice weekly [2,000 group]) against a higher dose (10,000 U times three [10,000 group]). Eighty-four patients were treated with chemotherapy. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 instrument. RESULTS: At baseline, mean B-Hb was 108 g/L with no difference between the groups. In the 10,000 group, an increase in B-Hb (>10 g/L) was seen in 30 (73%) patients treated with chemotherapy, after a median of 4 weeks, whereas a corresponding increase in the 2,000 group was seen in 15 (30%) patients after a median of 10 weeks (P < .001). A difference in the proportion of responders (five of eight v one of eight) was also seen in the group of patients not treated with chemotherapy. The proportion of responders was independent of baseline endogenous serum EPO level or observed/predicted log10 serum (S)-EPO levels. Patients who demonstrated improved B-Hb levels also showed improvements in QoL parameters. Tumor response was usually also associated with QoL improvements. CONCLUSION: Treatment with EPO at a dose of 10,000 U thrice weekly can rapidly and safely increase B-Hb levels in a high proportion of patients with advanced gastrointestinal cancers. QoL is influenced by the B-Hb increase, but also by the course of the underlying malignancy. It is therefore difficult to define clearly the clinical relevance of the B-Hb increase as such.

Adult↗
PubMed1998

Superoxide dismutase isoenzymes in the human eye.

PURPOSE: The authors determined the levels of the secreted, interstitially located extracellular superoxide dismutase (EC-SOD), the cytosolic copper- and zinc-containing SOD (CuZn-SOD), and the mitochondrial manganese-containing SOD (Mn-SOD) in tears, cornea, sclera, aqueous humor, lens, vitreous body, and retina of the human eye. METHODS: SOD enzymatic activity was determined by the direct spectrophotometric method using KO2. The amounts of EC-SOD and CuZn-SOD protein were also determined using enzyme-linked immunosorbent assay. RESULTS: Tears, aqueous humor, and vitreous body contained little SOD activity. Here ascorbate is the major scavenger of superoxide radicals. Of the ocular tissues studied, the lens contained the least SOD activity, 15-fold less than that of the average human tissue. The majority came from CuZn-SOD, but the lens also contained considerable amounts of inactive enzyme. There was some Mn-SOD, but the EC-SOD content was negligible. The cornea and sclera contained several times more SOD activity than the lens, and the EC-SOD contents were equal to or larger than those of CuZn-SOD. The retina contained much CuZn-SOD activity, but the EC-SOD and Mn-SOD activities were low. CONCLUSIONS: Ocular tissues and fluids, except for those in the retina, are less protected against superoxide radicals than extraocular tissues and fluids. The large amounts of EC-SOD in the sclera and cornea may be related to the risk for photochemical production of superoxide in these tissues. If inflammatory reactions occur, ocular tissues are at risk for damage induced by superoxide radicals and peroxynitrite, the reaction product with nitric oxide.

Adult↗
PubMed1997

Some details of the reaction mechanism of glucoamylase from Aspergillus niger--kinetic and structural studies on Trp52-->Phe and Trp317-->Phe mutants.

Presteady and steady-state kinetic results on the interactions of a wild-type, and the mutant glucoamylases Trp52-->Phe and Trp317-->Phe, from Aspergillus niger with maltose, maltotriose and maltotetraose have been obtained and analyzed. The results are compared with previous ones on the mutants, Trp120-->Phe and Glu180-->Gln, and with results obtained from structure energy minimization calculations based on known three-dimensional structural data. All results are in accordance with a three-step reaction model involving two steps in the substrate binding and a rate-determining catalytic step. Trp317 and Glu180 belong to different subsites, but are placed on the same flank of the active site (beta-flank). The Trp317-->Phe and the Glu180-->Gln mutants show almost identical kinetic results: weakening of the substrate binding, mainly caused by changes in the second reaction step, and practically no change of the catalytic rate. Structure energy minimization calculations show that the same loss of Arg305 and Glu180 hydrogen bonds to the substrate occurs in the Michaelis complexes of each of these mutants. These results indicate that important interactions of the active site may be better understood from a consideration of its flanks rather than of its subsites. The results further indicate differences in the substrate binding mode of maltose and of longer substrates. Trp52 and Trp120 each interact with the catalytic acid, Glu179, and are placed on the flank (alpha-flank) of the active site opposite to Trp317, Arg305 and Glu180. Also the Trp52-->Phe and Trp120-->Phe mutants show kinetic results similar to each other. The catalytic rates are strongly reduced and the substrates are bound more strongly, mainly as a result of the formation of a more stable complex in the second reaction step. All together, the substrate binding mechanism seems to involve an initial enzyme-substrate complex, in which the beta-flank plays a minor role, except for maltose binding; this is followed by a conformational change, in which hydrogen bonds to Arg305 and Glu180 of the beta-flank are established and the correct alignment on the alpha-flank of Glu179, the general acid catalyst, governed by its flexible interactions with Trp52 and Trp120, occurs.

Aspergillus niger↗
PubMed1997

Improved activity and modulated action pattern obtained by random mutagenesis at the fourth beta-alpha loop involved in substrate binding to the catalytic (beta/alpha)8-barrel domain of barley alpha-amylase 1.

The functionality of the sequence Arg183-Gly184-Tyr185 of the substrate binding fourth beta-alpha loop in the (beta/alpha)8-barrel of barley alpha-amylase isozyme 1 (AMY1) was studied by random mutagenesis. A motif of polar Gly184 hydrophobic residues was present in active mutants, selected by starch plate screening of yeast transformants. Gly184 was important, probably due to the carbonyl group binding to Ca2+ and the spatial proximity of Phe181. Mutation of both flanking residues as in Ser183-Gly184-Met185 (SGM-) and TGL-AMY1 decreased the Ca2+ affinity. SGM-AMY1 has 2-fold increased activity for amylose but reduced activity on maltooligosaccharides, whereas KGY-AMY1 has up to 3-fold elevated activity toward the oligosaccharides. TGL-AMY1 has modest activity on all substrates. Shifted action pattern on maltooligosaccharides for NGY-, SGM-, and TGL-AMY1 support that Arg183 in wild type is located at subsites +1 and +2, accommodating two sugar rings toward the reducing end from the site of cleavage. In the crystal structure of barley alpha-amylase 2 (AMY2), Lys182 (equivalent to AMY1 Arg183) is hydrogen-bonded with sugar OH-3 in subsite +2. Higher Ki app for acarbose inhibition of KGY-AMY1 and parent AMY1 compared with the other mutants suggests favorable substrate interactions for Arg/Lys183. KGY-AMY1 was not inhibited by the AMY2-specific proteinaceous barley alpha-amylase/subtilisin inhibitor, although Lys182 of AMY2 is salt-linked to the inhibitor.

Blotting, Western↗
PubMed1997

Overexpression and characterization of Aspergillus awamori wild-type and mutant glucoamylase secreted by the methylotrophic yeast Pichia pastoris: comparison with wild-type recombinant glucoamylase produced using Saccharomyces cerevisiae and Aspergillus niger as hosts.

Glucoamylase from Aspergillus niger (identical to Aspergillus awamori glucoamylase) is an industrially important, multidomain N- and O-glycosylated starch-hydrolase. To produce protein-engineered glucoamylase, heterologous expression is established in the methylotrophic yeast Pichia pastoris. Using the vector pHIL-D2, the cDNA encoding A. awamori glucoamylase is inserted in the yeast genome downstream of the 5' AOX1 promoter to replace the AOX1 gene. Induction by 0.75% methanol for 48 h led to synthesis of secreted glucoamylase to give around 0.4 g/liter, as directed by the A. awamori signal sequence. Recombinant glucoamylase produced in P. pastoris, Saccharomyces cerevisiae, or A. niger displayed similar catalytic properties, thiol content, and isoelectric point. Glucoamylase from P. pastoris, however, has higher thermostability than the enzymes from S. cerevisiae, A. niger, or a commercial preparation of A. niger glucoamylase. The average Mr determined by matrix-assisted laser desorption ionization mass spectrometry of these enzymes is thus 82,327, 83,869, 82,839, and 80,370, respectively, and neutral sugar analysis shows the differences to be due to variation in the extent of glycosylation. Compared to wild-type, single-residue mutation generally reduced the amount of secreted glucoamylase in S. cerevisiae and A. niger. In P. pastoris, however, the Cys320 --> Ala/Glu400 --> Cys double mutant is produced at 0.3 g/liter, or 75% of wild-type glucoamylase, while the corresponding single mutants have been produced at l and 20% of the wild-type level in S. cerevisiae and A. niger, respectively.

Aspergillus niger↗
PubMed1997

Domain evolution in the alpha-amylase family.

The available amino acid sequences of the alpha-amylase family (glycosyl hydrolase family 13) were searched to identify their domain B, a distinct domain that protrudes from the regular catalytic (beta/alpha)8-barrel between the strand beta3 and the helix alpha3. The isolated domain B sequences were inspected visually and also analyzed by Hydrophobic Cluster Analysis (HCA) to find common features. Sequence analyses and inspection of the few available three-dimensional structures suggest that the secondary structure of domain B varies with the enzyme specificity. Domain B in these different forms, however, may still have evolved from a common ancestor. The largest number of different specificities was found in the group with structural similarity to domain B from Bacillus cereus oligo-1,6-glucosidase that contains an alpha-helix succeeded by a three-stranded antiparallel beta-sheet. These enzymes are alpha-glucosidase, cyclomaltodextrinase, dextran glucosidase, trehalose-6-phosphate hydrolase, neopullulanase, and a few alpha-amylases. Domain B of this type was observed also in some mammalian proteins involved in the transport of amino acids. These proteins show remarkable similarity with (beta/alpha)8-barrel elements throughout the entire sequence of enzymes from the oligo-1, 6-glucosidase group. The transport proteins, in turn, resemble the animal 4F2 heavy-chain cell surface antigens, for which the sequences either lack domain B or contain only parts thereof. The similarities are compiled to indicate a possible route of domain evolution in the alpha-amylase family.

Amino Acid Sequence↗
PubMed1997

Postero-anterior radiogram of the knee in weight-bearing and semiflexion. Comparison with MR imaging.

PURPOSE: The purpose was four-fold: to assess the reproducibility of p.a. weight-bearing radiograms of the knee and the minimal joint-space (MJS) width measurements in these radiograms; to compare the MJS with MR-detected cartilage defects; to evaluate the location of these cartilage defects; and to estimate the relation between meniscal abnormalities and joint-space narrowing. MATERIAL AND METHODS: Fifty-nine individuals, aged 41-58 years (mean 50), with chronic knee pain were examined by means of p.a. weight-bearing radiograms in semiflexion with fluoroscopic guidance of the knee joint. The MJS was measured with a standard ruler. On the same day MR imaging was performed with proton-density- and T2-weighted turbo spin-echo on a 1.0 T imager. Meniscal abnormalities and cartilage defects in the tibiofemoral joint (TFJ) were noted. RESULTS AND CONCLUSION: The p.a. view of the knee and the MJS measurements were reproducible. MJS of 3 mm is a limit in diagnosing joint-space narrowing in knees with MR-detected cartilage defects. There was a high proportion (p < 0.001) of meniscal abnormality within the narrowed compartments in comparison with those that were not narrowed. A larger number of the cartilage defects (p < 0.05) was found in the medial femoral condyle than in any of the other condyles of the TFJ. The defects had a dorsal location (p < 0.001) as shown in the weight-bearing radiograms of the knee in semiflexion.

Adult↗
PubMed1997

Glucoamylase mutants in the conserved active-site segment Trp170-Tyr175 located at a distance from the site of catalysis.

To mimic the structure of the 1.8-fold more active (k(cat)) Rhizopus oryzae glucoamylase (GA), Aspergillus niger GA was subjected to site-directed mutagenesis in the Trp170-Tyr175 segment of the third of the six well-conserved alpha-->alpha connecting loops of the catalytic (alpha/alpha)6-barrel. While the Trp170-->Phe, Gln172-->Asn and Tyr175-->Phe mutants showed an up to 1.7-fold increased k(cat) and Gly174-->Cys GA and approximately 2-fold reduced k(cat) towards maltotriose and longer substrates, Asn171-->Ser, Thr173-->Gly and A.niger wild-type GA had very similar kcat and K(m) values for the hydrolysis of isomaltose and the malto-oligosaccharides of DP 2-7. Crystal structures of pseudotetrasaccharide inhibitor complexes of Aspergillus awamori var. X100 GA, which is 94% identical to A.niger GA, indicate that Tyr175 is located at binding subsite 4, while the preceding target residues and the high-mannose type unit on Asn171 are at a larger distance from the site of catalysis. The mutations had a modest effect on thermostability; the temperature for 50% inactivation, Tm, was thus unchanged for Tyr175 -->Phe GA and reduced by 0.2-2.9 degrees C for the other mutants. The deletion of the N-linked high-mannose unit-in Asn171 -->Ser and Thr173-->Gly GAs-appeared to be of minor importance for enzyme activity and thermostability, and did not increase the sensitivity to proteolysis.

Amino Acid Sequence↗
PubMed1997

Detection of joint pathology by magnetic resonance imaging in patients with early rheumatoid arthritis.

Magnetic resonance imaging (MRI) permits the visualization of anatomical structures not appreciated by conventional radiographic imaging, and may assess inflammatory disease and its progression with greater sensitivity than conventional radiography. In this study of 30 patients with early rheumatoid arthritis (RA), which could be considered as a pilot study because of the relatively small number of patients, we compare MRI of the knee and the fifth metatarsophalangeal joint with clinical and radiographic findings. A parallel study of 10 healthy individuals served as a reference group. In all but one of the 30 patients, MRI revealed some kind of joint abnormality, whereas conventional radiography was normal in 14 patients. The present study thus suggests that MRI may detect inflammatory and/or destructive joint changes in patients with early RA, and that these changes may occur in the absence of clinical symptoms or signs and/or radiographic signs in the examined joint. If these data prove to be confirmed in further controlled studies, MRI may be of importance both for the assessment of prognosis and for the decision to treat in the early critical stages of RA.

Adult↗
PubMed1997

Cartilage markers in synovial fluid in symptomatic knee osteoarthritis.

OBJECTIVE: To investigate if the relative content of aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid lavage samples differs between individuals with knee pain with or without evidence of radiological knee osteoarthritis (joint space narrowing). METHODS: In a community based cohort of 204 individuals aged 35-54 years with chronic (> 3 months duration) knee pain, a subgroup of 45 subjects with radiographic osteoarthritis, grade I according to the Ahlbäck classification, was randomly chosen; 45 individuals, age and sex matched from the same cohort with chronic knee pain but with normal radiographs, served as controls, Knee joint fluid was obtained by a standardised lavage procedure. The concentrations of aggrecan core protein epitopes and a cartilage matrix protein (COMP) were determined by immunoassays and the aggrecan/COMP concentration ratio was calculated. RESULTS: The aggrecan/COMP ratio was higher (P < 0.001) in the group with radiographic osteoarthritis than in the control group. CONCLUSIONS: The higher aggrecan/COMP ratios in osteoarthritis could reflect increased cartilage matrix turnover in osteoarthritis with predominant release of aggrecan fragments. Synovial fluid analysis of cartilage markers holds promise as a useful means of monitoring changes in the cartilage turnover in studies of pathogenic mechanisms in osteoarthritis.

Adult↗