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Biomedical subjects

J Olsson

Publications and source records attributed to J Olsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study.

AIMS/HYPOTHESIS: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin. METHODS: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion. RESULTS: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively. CONCLUSION/INTERPRETATION: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.

Blood Glucose↗
PubMed2000

Analysis of rat plasma proteins desorbed from gold and methyl- and hydroxyl-terminated alkane thiols on gold surfaces.

It is believed that adsorbed blood or plasma components, such as water, peptides, carbohydrates and proteins, determine key events in the concomitant inflammatory tissue response close to implants. The aim of the present study was to develop a procedure for the collection and analysis of minor amounts of proteins bound to solid metal implant surfaces. The combination of a sodium dodecyl sulfate washing method coupled with a polyacylamide gel electrophoretic protein separation technique (SDS-PAGE), Western blot and image analysis enabled the desorption, identification and semiquantification of specific proteins. The analyzed proteins were albumin, immunoglobulin G, fibrinogen and fibronectin. Concentration procedures of proteins were not required with this method despite the small area of the test surfaces. The plasma proteins were adsorbed to pure gold and hydroxylated and methylated gold surfaces, which elicit different tissue responses in vivo and plasma protein adsorption patterns in vitro. The image analysis revealed that the pure gold surfaces adsorbed the largest amount of total and specific proteins. This is in accordance with previous ellipsometry/antibody experiments in vitro. Further, the principles described for the protein analysis can be applied on implant surfaces ex vivo.

Journal Article↗
PubMed2000

Sex-determining region Y-related protein SOX13 is a diabetes autoantigen expressed in pancreatic islets.

The SOX (sex-determining region [SRY]-type high mobility group [HMG] box) family of transcription factors play key roles in determining cell fate during organ development. In this study, we have identified a new human SOX gene, SOX13, as encoding the type 1 diabetes autoantigen, islet cell antigen 12 (ICA12). Sequence analysis showed that SOX13 belongs to the class D subgroup of SOX transcription factors, which contain a leucine zipper motif and a region rich in glutamine. SOX13 autoantibodies occurred at a significantly higher frequency among 188 people with type 1 diabetes (18%) than among 88 with type 2 diabetes (6%) or 175 healthy control subjects (4%). Deletion mapping of the antibody epitopes showed that the autoantibodies were primarily directed against an epitope requiring the majority of the protein. SOX13 RNA was detected in most human tissues, with the highest levels in the pancreas, placenta, and kidney. Immunohistochemistry on sections of human pancreas identified SOX13 in the islets of Langerhans, where staining was mostly cytoplasmic. In mouse pancreas, Sox13 was present in the nucleus and cytoplasm of beta-cells as well as other islet cell types. Recombinant SOX13 protein bound to the SOX consensus DNA motif AACAAT, and binding was inhibited by homodimer formation. These observations-along with the known molecular interactions of the closely related protein, rainbow trout Sox23-suggest that SOX13 may be activated for nuclear import and DNA binding through heterodimer formation. In conclusion, we have identified ICA12 as the putative transcription factor SOX13 and demonstrated an increased frequency of autoantibody reactivity in sera from type 1 diabetic subjects compared with type 2 diabetic and healthy control subjects.

Amino Acid Sequence↗
PubMed1999

HIV-1 exposed dendritic cells show increased pro-inflammatory cytokine production but reduced IL-1ra following lipopolysaccharide stimulation.

OBJECTIVES: Dendritic cells (DC) are potential first target cells in sexually transmitted HIV-1 infection. They are also considered to be central in the activation of naive T cells, which thereupon can become permissive for HIV-1. In addition, activated DC express effector molecules, which likely contribute to the direction of T helper (Th1/Th2)-specific immune responses. METHODS: The capacity of cytokine and chemokine production in in vitro DC infected and uninfected with HIV-1 was assessed by enzyme-linked immunosorbent assay (ELISA) and by in situ immunocytochemical detection at the single cell level. Fluorescent in situ 5'-nuclease assay (FISNA) was used for quantitative evaluation of HIV-1 gag-positive cells. RESULTS: Macrophage-tropic HIV-1 effectively infected 20-40% of in vitro cultured DC. However, this activity alone did not induce detectable cytokine or chemokine protein expression in DC. In contrast, lipopolysaccharide (LPS) stimulation of these HIV-1-infected DC resulted in a significantly increased level of cells producing tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 1beta but reduced frequencies of cells producing IL-1 receptor antagonist (IL-1ra) compared with the LPS-stimulated but uninfected DC cultures (P < 0.05). Furthermore, an extensive production of the beta-chemokines [RANTES, macrophage inflammatory proteins (MIP) 1alpha and 1beta] was detected in DC in response to both LPS and HIV-1 plus LPS. CONCLUSIONS: These findings indicate that HIV-1 infected DC may have an increased proinflammatory activity. Elevated production of cytokines such as TNF-alpha and IL-1beta and reduced IL-1ra may contribute to enhanced replication of HIV-1 in bystander T cells. Gram-negative bacterial infection and gut-associated bacterial translocation in HIV-1-infected individuals may also result in endotoxin-mediated reactivation of HIV-1 in bystander CD4 CD45RO T cells caused by the increased production of proinflammatory cytokines in DC.

Cells, Cultured↗
PubMed1999

Dietary iron overload inhibits carbon tetrachloride-induced promotion in chemical hepatocarcinogenesis: effects on cell proliferation, apoptosis, and antioxidation.

BACKGROUND/AIMS: The aim of this study was to investigate if feeding with carbonyl iron would facilitate the development of preneoplastic lesions initiated by diethylnitrosamine (DEN) and promoted by CCl4-induced liver cirrhosis. METHODS: Male Wistar rats were fed a diet with 1.25%-2.5% carbonyl iron for 23 weeks and received intragastric injections of CCl4 (1.0 or 2.0 ml/kg per week) for 13 weeks, followed by one i.p. injection of DEN (200 mg/kg), after which CCl4 was administered for 8 additional weeks. Animals were killed 48 h after the first CCl4 injection to evaluate liver necrosis, 8 weeks later to evaluate fibrosis, and 9 weeks after DEN to determine formation of glutathione S-transferase 7,7 (GST-7,7) positive foci. RESULTS: Treatment with iron counteracted the increased serum alanine aminotransferase levels and liver necrosis following CCl4 administration. Hepatic levels of reduced Q9 and alpha-tocopherol were elevated in rats treated with CCl4 and decreased in rats treated with iron compared to the controls. Fibrogenesis was not altered by iron treatment. Nine weeks after DEN initiation, the number and volume density of GST-7,7-positive foci in rats treated with CCl4 were significantly increased as compared with controls, but co-treatment with iron inhibited this increase. Apoptotic index was increased in iron-loaded livers, and labelling index (the fraction of S-phase hepatocytes) was decreased by co-treatment with iron in livers exposed to CCl4. CONCLUSION: Carbonyl iron depleted hepatic levels of antioxidants, it decreased CCl4-induced necrosis and cell proliferation, it enhanced apoptosis and did not facilitate fibrogenesis. These effects together may explain the suppression of CCl4-induced promotion after DEN initiation exerted by carbonyl iron in the present study.

Animals↗
PubMed1999

Glycine toxicity after high-dose i.v. infusion of 1.5% glycine in the mouse.

Glycine 1.5% is the most widely used irrigating fluid during endoscopic procedures. To investigate if glycine toxicity is a mechanism promoting a fatal outcome when the solution is absorbed, we administered glycine 200 or 300 ml kg-1 dissolved in sterile water or normal saline, and also normal saline alone, over 60 min by i.v. infusion to 100 mice under methoxyflurane anaesthesia. Survival rates were 29% after 1.5% glycine, 21% after 1.5% glycine in normal saline, 67% after normal saline and 100% in controls. Both solutions containing glycine induced bradycardia and prolongation of the PQ interval and QRS duration, while only 1.5% glycine increased the water content of the myocardium. These results suggest that glycine promotes bradycardia and death, regardless of whether hyponatraemia or hypo-osmolality is present. We conclude that glycine toxicity is an important factor that increases the risk of administration of an irrigating fluid.

Animals↗
PubMed1999

Stability of the interstitial matrix after crystalloid fluid loading studied by volume kinetic analysis.

To investigate if fluid therapy changes the prerequisites for the development of oedema, four i.v. infusions of Ringer's solution 25 ml kg-1 were given over 15 or 30 min in a randomized crossover study to 10 healthy male volunteers, aged 28-40 (mean 31) yr. Blood haemoglobin concentration, measured every 5 min for 90 min, and urinary excretion were used as input data for volume kinetic analysis. The results showed that the elimination rate constant (kr) was higher when another infusion had been given earlier on the same day (208 vs 140 ml min-1; P < 0.002) and the size of V1 was larger during the 15-min infusions (4.7 vs 3.2 litre; P < 0.02). However, the size of V2 and the rate constant for the exchange of fluid between V1 and V2 were similar during all infusions. We conclude that a fluid challenge makes elimination of further infused fluid more effective but does not change compliance with volume expansion in healthy volunteers.

Adult↗
PubMed1998

Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study.

Results from a previous longitudinal study indicated that a combination of high CD8 and low CD4 percentages and poor T cell proliferation in peripheral blood lymphocytes was associated with higher mortality in a subgroup of a sample of very old Swedish individuals. The present study examined whether those results could be confirmed at a subsequent 2-year time interval by investigating if additional individuals from the same original sample had developed the immune profile associated with higher mortality. Subgroups were formed by cluster analysis and similar to our previous results, this follow-up study identified a subgroup of subjects (n = 18) with an immune profile which again included high CD8, low CD4 percentages and poor mitogen response and was associated with higher mortality. Over the 2-year period 12 additional individuals: (1) Developed this immune profile; and (2) Could be identified by changes in their CD4:CD8 ratios which progressively decreased over the study period. These results confirm our original study and indicate that in this very old sample, over a subsequent 2 year period, additional individuals moved into the cluster at risk for higher mortality.

Aged↗
PubMed1998

Determination of malondialdehyde in rat brain by capillary zone electrophoresis.

A method for determination of malondialdehyde with capillary electrophoresis using UV detection at 267 nm has been developed. The buffer system consisted of 10 mM borax and 0.5 mM CTAB at pH 9.3. Malondialdehyde migrated as the first peak in the electropherogram at 2.6 min. Limit of detection was 1.2 microM corresponding to 7.8 pg. Malondialdehyde was determined before and after stimulating lipid peroxidation with the addition of ferrous ammonium sulphate to homogenates of rat brain tissue. Proteins were precipitated by boiling and removed from the brain homogenates with centrifugation. No further pretreatment was made before injecting the homogenates on the CE system. Non-precipitated homogenates could also be analyzed, but this required washing of the capillary with 0.1 M NaOH before introduction of the next sample.

Animals↗
PubMed1998

Man-made superantigens: Tumor-selective agents for T-cell-based therapy.

Superantigens (SAgs) are a collection of bacterial and viral proteins with potent immunostimulatory properties. SAgs bind to Major Histocompatibility Complex Class II (MHC II) molecules of antigen presenting cells (APCs) and activate a high frequency of T lymphocytes. To target a T-cell attack against tumor cells we genetically linked tumor-specific antibody Fab fragments to the SAg Staphylococcal enterotoxin A (SEA). Fab-SEA fusion protein efficiently targeted to solid tumors and induced a T-cell-mediated eradication of established metastases in animal models. Successful therapy was T-cell-dependent and required tumor specificity of the Fab moiety of the Fab-SEA fusion protein. Due to the high affinity of SAg for MHC II, a limitation of this approach was retention of Fab-SEA proteins in normal tissues expressing MHC II, which caused systemic immune activation and dose limiting toxicity. We recently solved the structure of SEA and applied structure-based drug design to develop a novel generation of 'man-made' SAg with improved pharmacological and pharmacokinetic properties. Mutation of the major MHC II binding site of SEA substantially reduced retention in MHC II(+) tissues and systemic toxicity, while local immune activation at targeted tumor sites was retained. The Fab-SEA mutants display a 10000-fold higher affinity for tumor tissue compared to normal tissue and the therapeutic window was improved >100-fold compared to native Fab-SEA protein. Thus protein engineering can be applied to convert harmful bacterial toxins into tolerable tumor-specific agents.

Journal Article↗
PubMed1998

Concentrated bovine colostral whey proteins from Streptococcus mutans/Strep. sobrinus immunized cows inhibit the adherence of Strep. mutans and promote the aggregation of mutans streptococci.

The aim of this study was to examine the effect of bovine colostral whey proteins from cows immunized with Streptococcus mutans/Strep. sobrinus on the adherence and aggregation of caries-inducing bacteria, i.e., mutants streptococci. Both adherence and aggregation are important phenomena in the bacterial colonization of the human oral cavity. In all adherence experiments there was a significant difference between treatments by immune product (IP; from immunized cows) and a control product (CP; a similar product from non-immunized cows). The adherence of 35S-labelled Strep. mutans cells (serotype c) to parotid saliva-coated hydroxyapatite (SHA) was dose-dependently inhibited by both IP and CP if SHA was coated with either product before exposure to bacteria, but markedly lower concentrations of IP than CP were effective. When instead of SHA the bacterial cells were pretreated with IP or CP, only IP strongly and dose-dependently inhibited streptococcal adherence. When bacteria, IP or CP, and SHA were incubated simultaneously, a significant difference between IP and CP treatments was again found. Further, IP effectively aggregated both Strep. mutans and Strep. sobrinus cells, whereas hardly any effect was seen with CP. Both IP and CP aggregated the control bacterium Strep. sanguis, which affected the adherence of the pretreated bacteria.

Animals↗
PubMed1998

Evaluation of a new threshold visual field strategy, SITA, in normal subjects. Swedish Interactive Thresholding Algorithm.

PURPOSE: We developed a new family of test algorithms. This is an evaluation in normal subjects. METHODS: One eye in each of twenty normal subjects, with a mean age of 37 years (range 26 to 59), was tested twice with each of the SITA, Full Threshold and Fastpac strategies of the Humphrey perimeter at 3 separate visits. Actual test times and number of stimulus exposures were compared. Test-retest variability and levels of threshold estimates were also calculated and compared between strategies. RESULTS: In all subjects test times were shortest with SITA, 6.14 minutes in average, which was 50% as compared to Full Threshold (p<0.001) with an average of 12.27 minutes, and a reduction of 16% as compared to Fastpac (mean 7.28 minutes, p<0.0001). SITA required 287 stimulus exposures on the average, significantly fewer (p<0.0001) than corresponding numbers with Full Threshold (mean of 404), and significantly more (p<0.0001) than with Fastpac (average 240). SITA results showed significantly lower test-retest variability than results obtained with Fastpac (p=0.0002), and just as low as those of the Full Threshold strategy (p=0.0979). Threshold values obtained with SITA were slightly higher than those produced by the other two strategies. CONCLUSIONS: The results confirm those of previously reported simulated tests, that improved test algorithms using advanced visual field models and mathematical analyses performed in real time may effectively shorten computerized perimetry tests, while achieving the same or better test quality than today's standard methods.

Adult↗
PubMed1998

Functional conservation of the effector protein translocators PopB/YopB and PopD/YopD of Pseudomonas aeruginosa and Yersinia pseudotuberculosis.

Virulent Yersinia species cause systemic infections in rodents, and Y. pestis is highly pathogenic for humans. Pseudomonas aeruginosa, on the other hand, is an opportunistic pathogen, which normally infects only compromised individuals. Surprisingly, these pathogens both encode highly related contact-dependent secretion systems for the targeting of toxins into eukaryotic cells. In Yersinia, YopB and YopD direct the translocation of the secreted Yop effectors across the target cell membrane. In this study, we have analysed the function of the YopB and YopD homologues, PopB and PopD, encoded by P. aeruginosa. Expression of the pcrGVHpopBD operon in defined translocation-deficient mutants (yopB/yopD) of Yersinia resulted in complete complementation of the cell contact-dependent, YopE-induced cytotoxicity of Y. pseudotuberculosis on HeLa cells. We demonstrated that the complementation fully restored the ability of Y. pseudotuberculosis to translocate the effector molecules YopE and YopH into the HeLa cells. Similar to YopB, PopB induced a lytic effect on infected erythrocytes. The lytic activity induced by PopB could be prevented if the erythrocytes were infected in the presence of sugars larger than 3 nm in diameter, indicating that PopB induced a pore of similar size compared with that induced by YopB. Our findings show that the contact-dependent toxin-targeting mechanisms of Y. pseudotuberculosis and P. aeruginosa are conserved at the molecular level and that the translocator proteins are functionally interchangeable. Based on these similarities, we suggest that the translocation of toxins such as ExoS, ExoT and ExoU by P. aeruginosa across the eukaryotic cell membrane occurs via a pore induced by PopB.

Amino Acid Sequence↗
PubMed1998

Composition of pellicles formed in vivo on tooth surfaces in different parts of the dentition, and in vitro on hydroxyapatite.

Saliva from the major salivary glands dominates different areas of the mouth. The parotid (PS) and submandibular/sublingual (SMS) saliva differ in their protein composition, and thus, the composition of pellicles formed in various parts of the dentition might vary. In this study, proteins incorporated in 60-min pellicles from the premolar and front regions of the mouths of 4 subjects were examined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting using antibodies to amylase, albumin, IgA, parotid saliva agglutinin, low molecular weight SMS mucin (MG2) and proline-rich proteins. Pellicles formed in vitro on hydroxyapatite using PS, SMS and whole saliva from the subjects were examined in a similar manner. The pellicles formed in vitro and in vivo showed a major difference in the appearance of albumin. Bands of albumin were clearly stained in the samples of in vivo pellicles but were not observed or hardly visible in Western blots from the experimental, in vitro pellicles. The sites in the dentition from which a specific protein was recovered could differ between the 4 individuals. The overall protein pattern of the pellicles showed, however, characteristics typical of the saliva which may prevail in the part of the mouth where the pellicles were formed. Thus, parotid saliva agglutinin, a receptor for Streptococcus mutans, was primarily found in the premolar part of the dentition. The mucin MG2, which may mediate the adherence of Streptococcus sanguis and Streptococcus oralis, was in no case clearly seen in pellicles from the premolar region of the upper jaw. The observed variations might be important to the establishment of microflora and tooth-related disease patterns in various parts of the dentition.

Agglutinins↗
PubMed1998

Agglutinin and acidic proline-rich protein receptor patterns may modulate bacterial adherence and colonization on tooth surfaces.

Bacterial binding to salivary proteins may in part account for individual differences in the colonization of tooth surfaces. High-molecular-weight glycoproteins, agglutinins, mediate S. mutans adherence, whereas acidic proline-rich proteins mediate adherence of other early-colonizing streptococci and Actinomyces. The aim of the present study was to examine the composition of adherence-related salivary proteins and dental plaque micro-organisms in three individuals with a low, moderate, and high capacity to mediate S. mutans adherence. The S. mutans (strain Ingbritt) binding activity resided with a 300-kDa agglutinin which was six-fold more prevalent in the high S. mutans binding saliva compared with the low one. Binding to all three salivas was completely blocked by a monoclonal anti-agglutinin antibody. The moderate S. mutans binding saliva was found to contain adherence-inhibiting components. Furthermore, the low and moderate S. mutans binding salivas mediated binding of A. naeslundii strain LY7 to a greater extent than the saliva with high S. mutans binding. The A. naeslundii binding activity resided with the acidic proline-rich proteins (APRPs) and paralleled the relative content of 106- and 150-residue APRPs. Low A. naeslundii binding coincided with an almost two-fold higher ratio of 106/150 APRPs compared with the high A. naeslundii binding saliva. During conventional gel filtration, a degradation of the acidic, basic, and glycosylated proline-rich proteins was evident in the saliva with high S. mutans and low A. naeslundii binding. This saliva donor had a comparably high rate of dental plaque formation, high counts of S. mutans, and low counts of other streptococci and Actinomyces.

Actinomyces↗
PubMed1997

Studies on genotoxic effects of iron overload and alcohol in an animal model of hepatocarcinogenesis.

BACKGROUND/AIMS: In order to examine whether iron and alcohol act synergistically during tumor initiation in vivo, we investigated the effects of dietary iron overload and a liquid ethanol-containing diet on the initiation phase of the Solt & Farber model of chemical hepatocarcinogenesis. METHODS: Following dietary supplementation with carbonyl iron for 8 weeks and ethanol pair-feeding according to Lieber deCarli for 5 weeks, animals were subjected to partial hepatectomy in order to induce regenerative cell proliferation and thereby "fix" putative DNA lesions. Levels of malondialdehyde, reduced and oxidized ubiquinone-9, alpha-tocopherol and 8-oxo-2'-deoxyguanosine were analyzed in liver tissue removed at the time of partial hepatectomy, and blood was collected for determination of alanine amino-transferase activities. Following a 2-week recovery period, promotion was achieved with 0.02% dietary 2-acetylaminofluorene and carbon tetrachloride. Two weeks after the completion of promotion, animals were sacrificed and the number of preneoplastic, glutathione S-transferase 7,7-positive lesions counted. Animals initiated with diethylnitrosamine served as a positive control group. RESULTS: Serum aminotransferase activities were significantly increased, and hepatic contents of ubiquinol-9 (reduced ubiquinone-9) were significantly decreased in animals exposed to the combination of iron and ethanol in comparison to the other groups. Livers from iron-treated animals had decreased levels of alpha-tocopherol and increased contents of malondialdehyde, whereas treatment with ethanol did not further enhance these alterations. Levels of 8-oxo-2'-deoxyguanosine were not significantly different in animals treated with iron, ethanol or iron + ethanol as compared with controls. The number of preneoplastic foci at the time of sacrifice was not increased in livers exposed to iron and/or ethanol as compared with those from control animals. As expected, the number of foci was significantly increased in positive controls which were initiated with diethylnitrosamine. CONCLUSIONS: Iron potentiated the cytotoxic effects of ethanol, resulting in increased serum aminotransferase activities and decreased hepatic contents of ubiquinol. However, the combination of iron and ethanol did not exert genotoxic effects detectable as enhanced hepatic levels of 8-oxo-2'-deoxyguanosine, or increased formation of preneoplastic, glutathione S-transferase 7,7-positive lesions in the Solt & Farber model of chemical hepatocarcinogenesis.

Alanine Transaminase↗
PubMed1997

An improved method to estimate frequency of false positive answers in computerized perimetry.

Reliability of patient performance in static computerized perimetry is important for evaluation of results. False positive answers tend to falsely increase measured threshold sensitivity. The frequency of false positive responses is traditionally measured by adding extra questions, catch trials, to the test. Catch trials are few and limited because of time constraints, leading to inexact estimates. We developed an improved method for estimation of false positive answers by using information already available in current ordinary computerized visual field testing, without increasing test time. We here describe the method and evaluate it in a prospectively collected material of 49 glaucoma eyes of 49 patients. The results show that the new method reduces measurement errors considerably and significantly as compared with the traditional catch trials method. Test-retest change was only half with the new method as compared to the traditional method of catch trials. Furthermore, it can reduce test time by eliminating the need to use catch trials to estimate the frequency of false positive responses.

Adult↗