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Biomedical subjects

Gunnar Johansson

Publications and source records attributed to Gunnar Johansson.

At least 19 recordsLinked to original sources

Interactions between model membranes and lignin-related compounds studied by immobilized liposome chromatography.

In order to elucidate the modes of interaction between lignin precursors and membranes, we have studied the influence of temperature, lipid composition and buffer composition on the partitioning of monolignol and dilignol model substances into phospholipid bilayers. The partitioning was determined by immobilized liposome chromatography, which is an established method for studies of pharmaceutical drugs but a new approach in studies of lignin synthesis. The temperature dependence of the retention and the effect of a high ammonium sulfate concentration in the mobile phase demonstrated that the interaction involved both hydrophobic effects and polar interactions. There was also a good correlation between the partitioning and the estimated hydrophobicity, in terms of octanol/water partitioning. The partitioning behavior of the model substances suggests that passive diffusion over the cell membrane is a possible transport route for lignin precursors. This conclusion is strengthened by comparison of the present results with the partitioning of pharmaceutical drugs that are known to pass cell membranes by diffusion.

Chromatography, Liquid↗

International Primary Care Respiratory Group (IPCRG) Guidelines: management of chronic obstructive pulmonary disease (COPD).

COPD is a common and under-diagnosed disease which is increasing in prevalence worldwide. A more aggressive and optimistic approach must be adopted towards its management in primary care. This IPCRG Guideline on the management of COPD in primary care is fully consistent with GOLD guidelines. It highlights the goals of COPD treatment and the need for spirometric testing to make the diagnosis. It covers the classification of the disease according to disease severity, non-pharmacologic therapy including smoking cessation, avoidance of risk factors, patient education, pharmacologic therapy including the use of oxygen treatment, the management of exacerbations, the role of pulmonary rehabilitation, and the need for monitoring and ongoing care for COPD patients.

Bronchodilator Agents↗

Effects on skeletal muscle glutathione status of ischemia and reperfusion following abdominal aortic aneurysm surgery.

Glutathione (GSH) is an important endogenous scavenger against reactive oxygen species. Elective abdominal surgery without ischemia and reperfusion leads to decreased muscle GSH concentrations 4-72 hr postoperatively without altering GSH redox status. In the present study, we investigated to what extent muscle GSH status was affected during and following elective abdominal aortic aneurysm repair. From patients (n = 10) undergoing abdominal aortic repair, thigh muscle specimens were taken preoperatively, at maximal ischemia, and at 10 min and 4, 24, and 48 hr of reperfusion. Specimens were analyzed for GSH, amino acids, and energy-rich compounds. At maximal ischemia, phosphocreatine decreased by 37% (p < 0.05) and lactate and creatine increased by 274% and 57% (p < 0.001 and 0.05), respectively, indicating ischemia during the clamping of aorta. Adenosine triphosphate, on the other hand, remained unaltered during the entire study period. Total GSH (tGSH) decreased by 46% at 24 hr and by 43% at 48 hr of reperfusion (p < 0.001), while reduced GSH decreased by 48% at 24 hr and by 44% at 48 hr (p < 0.001). The redox status (GSH/tGSH) of GSH and oxidized GSH remained unaltered. Among the constituent amino acids of GSH, glycine and cysteine remained unaltered while glutamine and glutamate decreased by 55% and 55%, respectively (p < 0.001). Abdominal aortic aneurysm repair induces metabolic alterations characteristic for ischemia. The antioxidative capacity in terms of muscle levels of GSH was decreased. However, the oxidative stress during reperfusion did not change GSH status more than what has been reported following abdominal surgery without ischemia and reperfusion. The results indicate that the oxidative stress elicited by elective abdominal aortic aneurysm repair is outbalanced by a compensated GSH metabolism not giving rise to an increased amount of oxidized GSH or an altered GSH redox status.

Aged↗

Quality of life after surgery for varicose veins and the impact of preoperative duplex: results based on a randomized trial.

In a prospective randomized study, we found that the addition of a preoperative duplex scan before varicose vein (VV) surgery reduced recurrences and reoperations after 2 years. The aim of the present study was to investigate whether this correlates with an improved quality of life (QoL). We studied 293 patients scheduled for VV surgery with or without preoperative duplex. QoL was assessed preoperatively at 1 month, 1 year, and 2 years with the Short Form-36 (SF-36). Scores were compared with matched reference groups from the Swedish population. The 237 complete responders (81%) had a mean age of 47 (range 22-73) years, 169 (71%) were women, and 43 (18%) had skin changes. Both groups of VV patients scored significantly worse than the reference group in the domain Bodily Pain preoperatively (p < 0.001) and better after 1 year (p = 0.04), with no difference found after 2 years. There was no significant difference in QoL between the duplex and control groups at any time. We conclude that preoperative duplex before VV surgery did not significantly improve QoL after 2 years in spite of improved surgical results. VV surgery per se improved QoL as measured with the SF-36.

Adult↗

Cost effectiveness of budesonide/formoterol for maintenance and reliever therapy versus salmeterol/fluticasone plus salbutamol in the treatment of asthma.

INTRODUCTION: Budesonide/formoterol (Symbicort) Maintenance And Reliever Therapy (SMART) is an effective and well tolerated treatment option for patients with asthma. We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate (Seretide) plus salbutamol (albuterol) as needed (Seretide) Fixed Combination [SFC]). STUDY DESIGN: A cost-effectiveness analysis was performed based on effectiveness and resource-utilisation data collected prospectively in a randomised, 12-month study performed in 2143 patients in 16 countries. Resource utilisation data were pooled and unit costs (euro, year 2003 values) from Italy, France, the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided. METHODS: Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1 second [FEV(1)] 73% predicted; mean inhaled corticosteroid [ICS] dose 884 microg/day) were randomised to SMART or SFC. The effectiveness measure used was the number of severe exacerbations per patient per year. Direct costs included medication use (budesonide/formoterol 160microg/4.5microg or salmeterol/fluticasone 50microg/100microg, 50microg/250microg or 50microg/500microg plus salbutamol) and nonmedication-related resource use, including days in hospital, emergency room visits, specialist or primary care physician visits and other healthcare provider contacts. Indirect costs, including the number of days when the patient or their carer was unable to attend to their normal daily activities, were also assessed. The study assumed a European societal perspective (i.e. including direct and indirect costs). RESULTS: Treatment with SMART resulted in significantly fewer severe exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per patient per year; p = 0.0025). Resource use was low in both groups. Medication costs accounted for the majority of the total costs. The increased effectiveness of SMART was achieved at a reduced or similar cost compared with SFC. SMART dominated when German unit costs were applied (i.e. there was a statistically significant reduction in both costs and number of exacerbations). In all other countries, the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided; however, this difference was not statistically significant. CONCLUSION: This analysis demonstrates that, compared with SFC, SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy, Germany, France and the UK. SMART provided a reduction in the number of severe exacerbations per patient per year, at no statistically significant increase in cost - or even at a lower cost - compared with SFC plus as-needed reliever salbutamol.

Adolescent↗

Allergy to pigeon tick (Argas reflexus) in Upper Silesia, Poland.

The pigeon tick Argas reflexus is avian ectoparasite that typically feeds on pigeons. When devoid of a natural host, the ticks can also attack humans. In Upper Silesia, southern Poland, people living in the vicinity of the birds' nesting sites are frequently bitten by A. reflexus. The bites can provoke serious allergic reactions, including fatal anaphylactic shock. In the present study, residents of 9 apartments invaded by pigeon ticks were invited to undergo medical examination, skin prick tests (SPT) and determination of specific IgE to A. reflexus. The test allergens were prepared of ticks collected on-site. Out of 18 residents living in the infested apartments, 15 accepted the invitation. In this group, 8 persons complained of tick-related health problems, positive SPT to A. reflexus were found in all of them, and specific IgE was detectable in 3 persons (range: 0.38-0.84 kUA/l; CAP class 1-2). Final clinical diagnoses were established of generalised urticaria with asthma in 1 person, generalised urticaria in another 1, and local allergic reactions to tick bites in the remaining 6. Among 7 symptom-free residents, all test results were negative. Besides the study group, the paper also describes the case of a person who developed hypersensitivity to A. reflexus as a child, after a few visits to an abandoned dovecote. 30 years later, positive SPT (++) and specific IgE (0.78 kUA/l; CAP class 2) were still present despite no further re-exposures. The article also discusses available pest control measures against A. reflexus.

Adolescent↗

The active component in the flax-retting system of the zygomycete Rhizopus oryzae sb is a family 28 polygalacturonase.

The zygomycete Rhizopus oryzae sb is a very efficient organism for retting of flax, the initial microbiological step in the process of making linen. An extracellular polygalacturonase, when isolated could perform retting, and therefore probably is the key component in the retting system of R. oryzae. This was purified and characterized. The purified enzyme has a molecular mass of 37,436 Da from mass spectrometric determination, an isoelectric point of 8.4, and has non-methylated polygalacturonic acid as its preferred substrate. Peptide sequences indicate that the enzyme belongs to family 28, in similarity with other polygalacturonases (EC. 3.2.1.15). It contains, however an N-terminal sequence absent in other fungal pectinases, but present in an enzyme from the phytopathogenic bacterium Ralstonia solanacearum. The biochemical background for the superior retting efficiency of R. oryzae sb is discussed.

Amino Acid Sequence↗

Fat intake and composition of fatty acids in serum phospholipids in a randomized, controlled, Mediterranean dietary intervention study on patients with rheumatoid arthritis.

BACKGROUND: We have previously reported that rheumatoid arthritis patients, who adopted a modified Cretan Mediterranean diet, obtained a reduction in disease activity and an improvement in physical function and vitality. This shift in diet is likely to result in an altered intake of fatty acids. Therefore, the objective of the present study was to examine the dietary intake of fatty acids, as well as the fatty acid profile in serum phospholipids, during the dietary intervention study presented earlier. RESULTS: From baseline to the end of the study, changes in the reported consumption of various food groups were observed in the Mediterranean diet group. The change in diet resulted in a number of differences between the Mediterranean diet group and the control diet group regarding the fatty acid intake. For instance, a lower ratio of n-6 to n-3 fatty acids was observed in the Mediterranean diet group, both assessed by diet history interviews (dietary intake) and measured in serum phospholipids. Moreover, the patients in the Mediterranean diet group that showed a moderate or better clinical improvement during the study (diet responders), had a higher reported intake of n-3 fatty acids and a lower ratio of n-6 to n-3 fatty acids compared to the patients with minor or no improvement. Also the fatty acid profile in serum phospholipids differed in part between the diet responders and the diet non-responders. CONCLUSION: The changes in the fatty acid profile, indicated both by dietary assessments and through fatty acids in s-phospholipids may, at least in part, explain the beneficial effects of the Cretan Mediterranean diet that we have presented earlier.

Journal Article↗

Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease.

Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.

Adrenal Cortex Hormones↗

Surface character of pulp fibres studied using endoglucanases.

The endoglucanase Cel5A from Trichoderma reesei and an endoglucanase from Aspergillus sp. (Novozym 476 from Novozyme A/S) were evaluated as probes for the surface properties of soft- and hardwood chemical pulp fibres. The hydrolysis time curves were in accordance with a two-phase degradation model described by a biexponential function. The kinetic parameters corresponding to the amount of fast and slow degraded parts of the substrate correlated to tensile index, relative bonded area and z-strength of the paper. All paper properties showing a correlation with enzyme kinetic parameters were related to fibre-fibre interactions. Fluorescence labelling of the reducing end groups in pulp fibres followed by enzyme treatment indicated that the fast substrate class corresponds to the population of "loose" cellulose chain ends not tightly associated with the bulk cellulose. The correlation between the parameters of enzyme kinetics and mechanical properties of the paper produced from the corresponding pulp found in this study should allow a rapid evaluation of the raw fibre material used in paper making process.

Aspergillus↗

Weight reduction is not a major reason for improvement in rheumatoid arthritis from lacto-vegetarian, vegan or Mediterranean diets.

OBJECTIVES: Several investigators have reported that clinical improvements of patients with rheumatoid arthritis (RA), from participating in therapeutic diet intervention studies, have been accompanied by loss of body weight. This has raised the question whether weight reduction per se can improve RA. In order to test this hypothesis, three previously conducted diet intervention studies, comprising 95 patients with RA, were pooled. Together with Age, Gender, and Disease Duration, change during the test period in body weight, characterised dichotomously as reduction or no reduction (dichoDeltaBody Weight), as well as Diet (dichotomously as ordinary diet or test diet), were the independent variables. Dependent variables were the difference (Delta) from baseline to conclusion of the study in five different disease outcome measures. DeltaESR and DeltaPain Score were both characterised numerically and dichotomously (improvement or no improvement). DeltaAcute Phase Response, DeltaPhysical Function, and DeltaTender Joint Count were characterised dichotomously only. Multiple logistic regression was used to analyse associations between the independent and the disease outcome variables. RESULTS: Statistically significant correlations were found between Diet and three disease outcome variables i.e. DeltaAcute-Phase Response, DeltaPain Score, and DeltaPhysical Function. Delta Body Weight was univariately only correlated to DeltaAcute-Phase Response but not significant when diet was taken into account. CONCLUSION: Body weight reduction did not significantly contribute to the improvement in rheumatoid arthritis when eating lacto-vegetarian, vegan or Mediterranean diets.

Activities of Daily Living↗

Organisation of asthma care in primary health care in Mid-Sweden.

AIM: To investigate the organisation of asthma care in 240 primary health care centres (PHCCs) in Mid-Sweden. METHODS: A cross-sectional study. Main outcomes were occurrence and structure of nurse-based asthma clinics according to nationally recommended criteria, and access and use of spirometers. RESULTS: 238 PHCCs (99%) responded. 16% reported a complete, and 37% an incomplete, asthma clinic. 47% of PHCCs had no asthma clinic. The incomplete asthma clinics usually lacked sufficient asthma nurse time, a scheduled nurse surgery and a responsible GP. 77% of the PHCCs had access to a spirometer and on average 19 spirometries/1000 inhabitants/year were performed. There was a large variation in the use of spirometers. CONCLUSION: Half of the PHCCs had an asthma clinic and a majority had access to a spirometer. More frequent use of spirometry and increased time provision for the asthma nurse would be likely to produce a substantial improvement in the standard of asthma care in primary health care.

Journal Article↗

Processive action of cellobiohydrolase Cel7A from Trichoderma reesei is revealed as 'burst' kinetics on fluorescent polymeric model substrates.

Reaction conditions for the reducing-end-specific derivatization of cellulose substrates with the fluorogenic compound, anthranilic acid, have been established. Hydrolysis of fluorescence-labelled celluloses by cellobiohydrolase Cel7A from Trichoderma reesei was consistent with the active-site titration kinetics (burst kinetics), which allowed the quantification of the processivity of the enzyme. The processivity values of 88+/-10, 42+/-10 and 34+/-2.0 cellobiose units were found for Cel7A acting on labelled bacterial cellulose, bacterial microcrystalline cellulose and endoglucanase-pretreated bacterial cellulose respectively. The anthranilic acid derivatization also provides an alternative means for estimating the average degree of polymerization of cellulose and, furthermore, allows the quantitative monitoring of the production of reducing end groups on solid cellulose on hydrolysis by cellulases. Hydrolysis of bacterial cellulose by cellulases from T. reesei revealed that, by contrast with endoglucanase Cel5A, neither cellobiohydrolases Cel7A nor Cel6A produced detectable amounts of new reducing end groups on residual cellulose.

Binding Sites↗

Changes in superficial and perforating vein reflux after varicose vein surgery.

OBJECTIVES: This prospective duplex study was conducted to study the effect of current surgical treatment for primary varicose veins on the development of venous insufficiency < or = 2 years after varicose vein surgery. METHODS: The patients were part of a randomized controlled study where surgery for primary varicose veins was planned from a clinical examination alone or with the addition of preoperative duplex scanning. Postoperative duplex scanning was done at 2 months and 2 years. RESULTS: Operations were done on 293 patients (343 legs), 74% of whom were women. The mean age was 47 years. In 126 legs, duplex scanning was done preoperatively, at 2 months and 2 years, and at 2 months and 2 years in 251 legs. Preoperative perforating vein incompetence (PVI) was present in 64 of 126 legs. Perforator ligation was not done on 42 of these; at 2 months, 23 of these legs (55%) had no PVI, and at 2 years, 25 legs (60%) had no PVI. Sixty-one legs had no PVI preoperatively, 5 (8%) had PVI at 2 months, and 11 (18%) had PVI at 2 years. In the group of 251 legs, reversal of PVI between 2 months and 2 years was found in 28 (41%) of 68 and was more common than new PVI, which occurred in 41 (22%) of 183 (P = .003). After 2 years, the number of legs without venous incompetence in which perforator surgery was not performed was 11 (26%) of 42 legs with preoperative PVI and 18 (30%) of 61 legs without preoperative PVI, (P = .713). After 2 years, new vessel formation was more common in the surgically obliterated saphenopopliteal junction (SPJ), 4 (40%) of 10, than in the saphenofemoral junction (SFJ), 17 (11%) of 151(P = .027), and new incompetence in a previously normal junction was more common in the SFJ, 11 (18%) of 63, than in the SPJ, 3 (1%) of 226 (P < .001). Reflux in the great saphenous vein (GSV) below the knee was abolished after stripping above the knee in 17 (34%) of 50 legs at 2 months and in 22 legs (44%) after 2 years. CONCLUSIONS: Varicose vein surgery induces changes in the remaining venous segments of the legs that continue for several months. In most patients, perforators and the GSV below the knee can be ignored at the primary surgery. A substantial number of recurrences in the SFJ and SPJ are unavoidable with present surgical knowledge because they stem from new vessel formation and progression of disease.

Female↗

Inhibition of the Trichoderma reesei cellulases by cellobiose is strongly dependent on the nature of the substrate.

The inhibition effect of cellobiose on the initial stage of hydrolysis when cellobiohydrolase Cel 7A and endoglucanases Cel 7B, Cel 5A, and Cel 12A from Trichoderma reesei were acting on bacterial cellulose and amorphous cellulose that were [(3)H]- labeled at the reducing end was quantified. The apparent competitive inhibition constant (K(i)) for Cel 7A on [(3)H]-bacterial cellulose was found to be 1.6 +/- 0.5 mM, 100-fold higher than that for Cel 7A acting on low-molecular-weight model substrates. The hydrolysis of [(3)H]-amorphous cellulose by endoglucanases was even less affected by cellobiose inhibition with apparent K(i) values of 11 +/- 3 mM and 34 +/- 6 mM for Cel 7B and Cel 5A, respectively. Contrary to the case for the other enzymes studied, the release of radioactive label by Cel 12A was stimulated by cellobiose, possibly due to a more pronounced transglycosylating activity. Theoretical analysis of the inhibition of Cel 7A by cellobiose predicted an inhibition analogous to that of mixed type with two limiting cases, competitive inhibition if the prevalent enzyme-substrate complex without inhibitor is productive and conventional mixed type when the prevalent enzyme-substrate complex is nonproductive.

Acetobacterium↗

Determination of dissociation constants by competitive binding in partial filling capillary electrophoresis.

The determination of dissociation constands (K(d)) by competitive ligand binding in partial filling capillary electrophoresis is demonstrated. Two different strategies were applied, one of which only uses a single reporter ligand and a more elaborated one which suppresses systemic disturbances by using a racemic mixture as reporter. The dissociation constants obtained by both alternatives were virtually identical and in good agreement with those previously reported.

Alprenolol↗

Determination of protein-ligand affinity constants from direct migration time in capillary electrophoresis.

A simple method to calculate dissociation constants for protein-ligand interactions by partial-filling capillary electrophoresis is demonstrated. The method uses raw migration time data for the ligand and needs only additional information about capillary inner radius and the absolute amount of protein loaded. A theoretical study supported by experimental data also demonstrates that the retention of analyte in affinity capillary electrophoresis (ACE) using the partial-filling technique depends linearly on the absolute amount of selector added but is independent of both selector zone length and selector mobility. Factors such as field strength and electroosmotic flow are also cancelled out if they are kept constant. The theory is confirmed and the usefulness of the method is demonstrated by enantioseparations using alpha-acid glycoprotein (AGP) and cellulase (Cel 7A) as chiral selectors.

Algorithms↗

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↗