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Biomedical subjects

Gunnar Johansson

Publications and source records attributed to Gunnar Johansson.

32 records · Page 2Linked to original sources

Recent developments on cellulases and carbohydrate-binding modules with cellulose affinity.

This review concerns basic research on cellulases and cellulose-specific carbohydrate-binding modules (CBMs). As a background, glycosyl hydrolases are also briefly reviewed. The nomenclature of cellulases and CBMs is discussed. The main cellulase-producing organisms and their cellulases are described. Synergy, enantioseparation, cellulases in plants, cellulosomes, cellulases and CBMs as analytical tools and cellulase-like enzymes are also briefly reviewed.

Cellulases↗

Asthma treatment preference study: a conjoint analysis of preferred drug treatments.

OBJECTIVE: Assessment of patient preferences for attributes of asthma treatments. METHODS: Two hundred ninety-eight patients (age range, 18 to 60 years) from 15 centers in Sweden completed a questionnaire concerning their asthma, and ranked 18 alternative treatments using conjoint analysis. Patients were receiving treatment with either inhaled corticosteroids (ICS) and short-acting bronchodilator (n = 123) or ICS and long-acting bronchodilator (separate inhalers, n = 87; combination inhaler, n = 88). Attributes analyzed were maintenance treatment, additional reliever, time to onset and duration of reliever, number of symptom-free days (SFDs) per month, and out-of-pocket cost per month. RESULTS: Conjoint analysis showed that the most important aspect of treatment was SFD. Forty percent of the patients had <or= 15 SFDs per month. Eighty-five percent of the patients preferred another treatment over their current treatment. Treatment preferences were heterogeneous, and in 78% were not covered by current treatment guidelines. A total of 148 patients (50%) preferred a combination inhaler to separate inhalers, and 233 patients (78%) preferred a reliever that is both rapid and long acting. The most preferred treatment was a combination inhaler for maintenance and reliever use. On average, the patients were willing to pay an additional 328 Swedish krona [36 US dollars] per month for the change to the preferred treatment. CONCLUSION: SFDs were the most important attribute in asthma treatment. Patients were willing to pay for a switch to their preferred treatment. The most favored treatments were a reliever therapy that is both rapid and long acting and a combination inhaler for both maintenance and as-needed use.

Administration, Inhalation↗

Synergistic cellulose hydrolysis can be described in terms of fractal-like kinetics.

A fractal-like kinetics model was used to describe the synergistic hydrolysis of bacterial cellulose by Trichoderma reesei cellulases. The synergistic action of intact cellobiohydrolase Cel7A and endoglucanase Cel5A at low enzyme-to-substrate ratios showed an apparent substrate inhibition consistent with a case where two-dimensional (2-D) surface diffusion of the cellobiohydrolase is rate-limiting. The action of Cel7A core and Cel5A was instead consistent with a three-dimensional (3-D) diffusion-based mode of action. The synergistic action of intact Cel7A was far superior to that of the core at a high enzyme-to-substrate ratio, but this effect was gradually reduced at lower enzyme-to-substrate ratios. The apparent fractal kinetics exponent h obtained by nonlinear fit of hydrolysis data to the fractal-like kinetics analogue of a first-order reaction was a useful empirical parameter for assessing the rate retardation and its dependence on the reaction conditions.

Cellobiose↗

Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial.

BACKGROUND: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. OBJECTIVE: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. DESIGN: Randomized, controlled trial. SETTING: 600 office and clinical research sites. PATIENTS: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. INTERVENTION: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. MEASUREMENTS: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. RESULTS: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. CONCLUSIONS: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.

Anti-Inflammatory Agents, Non-Steroidal↗

Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis.

BACKGROUND: Previously we have reported that patients with rheumatoid arthritis (RA) obtained a significant reduction in disease activity by adopting a Mediterranean-type diet. The present study was carried out to investigate the antioxidant intake, the plasma levels of antioxidants and a marker of oxidative stress (malondialdehyde) during the study presented earlier. METHODS: RA patients randomized to either a Mediterranean type diet (MD group; n = 26) or a control diet (CD group; n = 25) were compared during a three month dietary intervention study. Their antioxidant intake was assessed by means of diet history interviews and their intake of antioxidant-rich foods by a self-administered questionnaire. The plasma levels of retinol, antioxidants (alpha- and gamma-tocopherol, beta-carotene, lycopene, vitamin C and uric acid) and urinary malondialdehyde (MDA), a marker for oxidative stress, were determined using high performance liquid chromatography. The Student's t-test for independent samples and paired samples were used to test differences between and within groups. For variables with skewed distributions Mann-Whitney U-test and Wilcoxon signed ranks test were performed. To evaluate associations between dietary intake of antioxidants, as well as between disease activity, MDA and antioxidants we used Pearson's product moment correlation or Spearman's rank correlation. RESULTS: The MD group had significantly higher intake frequencies of antioxidant-rich foods, and also higher intakes of vitamin C (p = 0.014), vitamin E (p = 0.007) and selenium (p = 0.004), and a lower intake of retinol (p = 0.049), compared to the CD group. However, the difference between the groups regarding vitamin C intake was not significant when under- and over-reporters were excluded (p = 0.066). There were no changes in urine MDA or in the plasma levels of antioxidants (after p-lipid adjustments of the tocopherol results), from baseline to the end of the study. The levels of retinol, vitamin C and uric acid were negatively correlated to disease activity variables. No correlation was found between antioxidant intake and the plasma levels of antioxidants. CONCLUSIONS: Despite an increase in reported consumption of antioxidant-rich foods during the Mediterranean diet intervention, the levels of plasma antioxidants and urine MDA did not change. However, the plasma levels of vitamin C, retinol and uric acid were inversely correlated to variables related to RA disease activity.

Clinical Trial↗

Migration time and peak area artifacts caused by systemic effects in voltage controlled capillary electrophoresis.

The effect of an artificial conductivity step on the migration time for rac-propranolol was investigated with the purpose to give a strict physical background to the intensively studied migration time and integration variations in voltage stabilized capillary electrophoresis. The experiments verified a theoretical derivation of migration time disturbances caused by the sometimes unavoidable conductivity variations in the system. The verified equation describing migration time variations was used for simulations of a number of relevant cases, such as variation in injected sample conductivity, post-injection diffusional broadening of the sample zone, and the physical effect of a selector zone in the partial filling mode. A similar theoretical and experimental treatment of the integration errors caused by non-uniform velocity was also included with special reference to enantiomer separation in the partial filling mode. The same experiments were also used to show that the standard migration time related method for integration correction fails if the velocity of a component is not constant throughout the experiment, such as the situation when a selector is employed in partial-filling mode.

Artifacts↗

Veganism as status passage: the process of becoming a vegan among youths in Sweden.

In a town in northern Sweden, 3.3% of the 15-year-old adolescents were vegans in 1996. This study describes the process of becoming a vegan among adolescents and interprets the informants' descriptions by constructing categories, which later on were related to relevant theories. Group interviews were conducted with three vegans and in-depth interviews were performed with three other vegan adolescents. The methodology was grounded theory and the adolescents' perceptions were analyzed in the framework of symbolic interactionism. Three types of vegans were identified: the Conformed Vegan, the Organized Vegan, and the Individualistic Vegan. The decision to become a vegan was reported to be influenced by perceived internal reasons such as ethics, health, distaste for meat, and preference for vegetarian food. In addition, friends, family, school, media, and music influenced the decision to become a vegan. The perceived consequences of becoming a vegan were positive as well as negative and differed between the three types of vegans. Veganism as a new type of status passage with specific characteristics was illustrated. No modifications or new properties were discovered that add to the theory of status passage which indicates that the general model is applicable also in a vegan context.

Adolescent↗

Use of a fluorescence labelled, carbohydrate-binding module from Phanerochaete chrysosporium Cel7D for studying wood cell wall ultrastructure.

UNLABELLED: The alpha-amino group of the carbohydrate-binding module (CBM) from Phanerochaete chrysosporium cellulase Cel7D was covalently labelled with fluorescein isothiocyanate. The fluorescein-labelled CBM was characterised regarding substrate binding, showing specificity only to cellulose and not to mannan and xylan. Conjugation of fluorescein isothiocyanate to CBM did not affect its binding to cellulose. The labelled CBM was successfully used as a probe for detecting cellulose in lignocellulose material such as never dried spruce and birch wood as well as pulp fibres. ABBREVIATIONS: Bmax, maximum binding capacity; BMCC, bacterial microcrystalline cellulose; CBH, cellobiohydrolase; CBM, carbohydrate-binding module; CBM-FITC, carbohydrate-binding module labelled with fluorescein isothiocyanate; CBM1, carbohydrate-binding module of family 1; FITC, fluorescein isothiocyanate; KD, dissociation constant; RP-HPLC, reversed phase HPLC; S1-S3, Secondary cell wall layers 1-3.

Betula↗

Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis.

Loss of axonal contact characterizes Schwann cells in benign and malignant peripheral nerve sheath tumors (MPNST) from neurofibromatosis type 1 (NF1) patients. Tumor Schwann cells demonstrate NF1 mutations, elevated Ras activity, and aberrant epidermal growth factor receptor (EGFR) expression. Using cDNA microarrays, we found that brain lipid binding protein (BLBP) is elevated in an EGFR-positive subpopulation of Nf1 mutant mouse Schwann cells (Nf1(-/-) TXF) that grows away from axons; BLBP expression was not affected by farnesyltransferase inhibitor, an inhibitor of H-Ras. BLBP was also detected in EGFR-positive cell lines derived from Nf1:p53 double mutant mice and human MPNST. BLBP expression was induced in normal Schwann cells following transfection with EGFR but not H-Ras12V. Furthermore, EGFR-mediated BLBP expression was not inhibited by dominant-negative H-Ras, indicating that BLBP expression is downstream of Ras-independent EGFR signaling. BLBP-blocking antibodies enabled process outgrowth from Nf1(-/-) TXF cells and restored interaction with axons, without affecting cell proliferation or migration. Following injury, BLBP expression was induced in normal sciatic nerves when nonmyelinating Schwann cells remodeled their processes. These data suggest that BLBP, stimulated by Ras-independent pathways, regulates Schwann cell-axon interactions in normal peripheral nerve and peripheral nerve tumors.

Animals↗

Cellobiose quinone oxidoreductase from the white rot fungus Phanerochaete chrysosporium is produced by intracellular proteolysis of cellobiose dehydrogenase.

The fungus Phanerochaete chrysosporium was grown in a 10-l automatic fermenter using cellobiose as carbon source to monitor the induction of cellobiose dehydrogenase (CDH) and cellobiose quinone oxidoreductase (CBQ) enzymes, and to search for tentative cbq and cdh genes and their transcriptional products. After 24 h of induction, CDH was detected in the culture supernatant and a protein was recognized by a specific anti-CDH polyclonal antibody in the sonicated biomass. Northern blot experiments performed with several fungal RNA samples showed, after 24 h of induction, only one single species of an mRNA transcript corresponding in size to the cdh gene (2.5 kb) The relative amount of this transcript decreased as a function of time. Southern blot experiments done with genomic DNA and database search in the recently available genome information also ruled out the presence in this strain of a separate cbq gene distinct from the cdh gene. Taken together, these results demonstrated that CBQ originates from the cdh gene. Furthermore, it is not produced by differential splicing but by a posttranslational, predominantly intracellular, proteolytic cleavage.

Alleles↗

A statistical experimental design to study factors affecting enantioseparation of propranolol by capillary electrophoresis with cellobiohydrolase (Cel7A) as chiral selector.

The capillary electrophoretic enantioseparation of rac-propranolol using cellobiohydrolase Tr Cel7A as selector was optimized by an unbiased statistical experimental design. A set of pre-experiments was performed in order to identify critical experimental factors. In the definitive chemometric design pH, ranging from 5 to 7, ionic strength ranging between 0.01 and 0.02 and organic solvent additive in concentration from 1 to 19% v/v were studied. The response surface plot revealed a separation optimum in the pH interval studied. When all parameters were taken into account, a background electrolyte consisting of 0.016 M bistris-acetate buffer with pH 6.5 and 17% v/v acetonitrile gave the optimum separation. The significance of the statistical design was confirmed by the generally good agreement obtained between predicted response and actual experimental data.

Buffers↗

Lifestyle-related characteristics of young low-meat consumers and omnivores in Sweden and Norway.

PURPOSE: To compare the lifestyle-related characteristics of low-meat consumer and omnivore adolescents in Sweden and Norway. METHODS: A total of 2041 students (578 from Umeå, Sweden; 504 from Stockholm, Sweden; and 959 from Bergen, Norway), with a mean age of 15.5 years, completed a questionnaire. Information was collected about physical characteristics, and health, family situation, social, exercise, alcohol, and tobacco habits. The response rate was 95% in Umeå, 91% in Stockholm, and 83% in Bergen. Statistical analyses included Chi-square and Mann-Whitney U tests. RESULTS: There was no reported difference between low-meat consumers and omnivores with respect to alcohol use, smoking, weight, or amount of exercise. Female low-meat consumers more frequently used smokeless tobacco, reported having more sick days during the last year, attached less importance to "being healthy," and had been depressed more often than female omnivores. Male low-meat consumers reported, to a greater extent than male omnivores, having been tired without reason, having often had headaches and having been depressed. Female low-meat consumers had parents with a higher average level of education than did female omnivores and more often spent time with friends after school. CONCLUSIONS: Vegetarianism or low-meat consumption is mainly a female phenomenon among adolescents in this study. The study indicates that the lifestyle of young low-meat consumers differs from the lifestyle found in previous studies of vegetarians with respect to the respondents' exercise habits, their perception of their own health, and their use of alcohol and tobacco. Contrary to findings from other studies, adherence to a low-meat diet may not correlate with other health promotion practices among adolescents in Sweden and Norway.

Adolescent↗

Dental analgesia produced by non-painful low-frequency stimulation is not influenced by stress or reversed by naloxone.

The dental pain threshold elevation produced by non-painful, low-frequency transcutaneous electrical nerve stimulation (TENS) in healthy humans was not reduced by the administration of 0.8 mg of naloxone i.v. Neither ACTH, prolactin nor growth hormone (GH) release were related to the pain threshold elevations. The present study indicates that the dental pain threshold elevation during non-painful, low-frequency TENS is not based on the same opioid-dependent mechanisms as the dental pain threshold elevation during acupuncture or the clinical analgesia during low-frequency TENS. Stress or other adenohypophyseal mechanisms involving ACTH, prolactin or GH do not explain the analgesia induced by non-painful, low-frequency TENS.

Adrenocorticotropic Hormone↗