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Biomedical subjects

A Gustafsson

Publications and source records attributed to A Gustafsson.

At least 19 recordsLinked to original sources

Cathodoluminescence studies of nanostructured semiconductors.

Spatially and spectrally resolved cathodoluminescence in the scanning electron microscope is a very powerful technique for studying the optical properties of semiconductor structures, especially low-dimensional structures (structures with nanometre-sized features). The technique is generally nondestructive and can be combined with the normal imaging capabilities and analysis possibilities of the scanning electron microscope. This article gives an introduction to the technique and a number of examples of the possibilities of the technique.

Journal Article↗

Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis.

OBJECTIVES: Stimulated mono- and polymorphonuclear cells from patients with periodontitis have shown increased release of interleukin-1beta (IL-1beta) and oxygen radicals, respectively. The aim was to study whether this hyper-reactivity could be found both in mono- and polymorphonuclear cells from the same patient, and whether there was a relation to the gene coding for IL-1beta (IL-1beta(+3953)). MATERIAL AND METHODS: Peripheral mononuclear cells from 14 non-smoking and well-treated patients and pair-matched controls were incubated with opsonized Staphylococcus aureus and lipopolysaccharide (LPS). Released IL-1beta and tumour necrosis factor (TNF)-alpha were determined with ELISA. Generation of oxygen radicals from the Fcgamma-receptor-stimulated neutrophils was measured with chemiluminescence and the polymorphism at IL-1beta(+3953) was measured with polymerase chainreaction. RESULTS: The mononuclear cells from the patients released more IL-1beta after incubation with LPS (p<0.001) and with bacteria (p<0.05). The release of TNF-alpha tended to be higher in the patient group. The peripheral neutrophils from the patients generated more oxygen radicals (p<0.06). We found no differences between the study groups regarding the IL-1beta(+3953) polymorphism. CONCLUSION: The similarity in systemic inflammation between patients and controls suggests that the increased release/generation of IL-1beta and oxygen radicals from peripheral leukocytes in periodontitis patients is of a constitutional nature and of pathogenic relevance.

Alleles↗

The short-term effects of low-level lasers as adjunct therapy in the treatment of periodontal inflammation.

OBJECTIVES: The aim of this split-mouth, double-blind controlled clinical trial was to study the effects of irradiation with low-level lasers as an adjunctive treatment of inflamed gingival tissue. MATERIALS AND METHODS: Seventeen patients with moderate periodontitis were included. After clinical examination, all teeth were scaled and root planed (SRP). One week after SRP, we took samples of gingival crevicular fluid (GCF) and subgingival plaque. The laser therapy was started 1 week later and continued once a week for 6 weeks. One side of the upper jaw was treated with active laser and the other with a placebo. The test side was treated with two low-level lasers having wavelengths of 635 and 830 nm. The patients then underwent another clinical examination with sampling of GCF and plaque. The GCF samples were analysed for elastase activity, interleukin-1beta (IL-1beta) and metalloproteinase-8 (MMP-8). We examined the subgingival plaque for 12 bacteria using DNA probes. RESULTS: The clinical variables i.e. probing pocket depth, plaque and gingival indices were reduced more on the laser side than on the placebo one (p<0.01). The decrease in GCF volume was also greater on the laser side, 0, 12 microl, than on the placebo side, 0.05 microl (p=0.01). The total amount of MMP-8 increased on the placebo side but was slightly lower on the laser side (p=0.052). Elastase activity, IL-1beta concentration and the microbiological analyses showed no significant differences between the laser and placebo sides. CONCLUSION: Additional treatment with low-level lasers reduced periodontal gingival inflammation.

Adult↗

Aberrant neutrophil reactions in periodontitis.

BACKGROUND: The aim of this study was to compare the activity of neutrophilic granulocytes in patients with severe periodontitis and patients with gingivitis alone. METHODS: The study population comprised 22 patients with gingivitis and 44 with periodontitis. Samples of gingival crevicular fluid (GCF) were collected from untreated patients with gingivitis and from shallow and deep pockets in untreated patients with periodontitis. GCF samples were analyzed for lactoferrin, elastase, matrix metalloproteinase-8 and -9, and collagenolytic activity. RESULTS: The free elastase activity and the neutrophil activity, estimated as the ratio between elastase and lactoferrin, were significantly higher in the samples from the periodontitis patients. These differences were also observed in shallow pockets in periodontitis patients compared to similar pockets in patients with gingivitis. CONCLUSION: This study shows higher levels of free elastase in untreated patients with periodontitis, relative to inflammation-matched controls, which may explain the tissue destruction seen in periodontitis.

Animals↗

The short-term effectiveness of non-surgical treatment in reducing protease activity in gingival crevicular fluid from chronic periodontitis patients.

OBJECTIVES: The aim of this study was to evaluate the short-term effect of non-surgical periodontal treatment on protease activity in gingival crevicular fluid (GCF) of patients with chronic periodontitis. MATERIAL AND METHODS: After clinical examination, in which pocket probing depth, probing attachment level, plaque and bleeding indices were recorded, gingival fluid samples from 21 chronic periodontitis patients were collected from gingivitis (GP) and periodontitis (PP) sites with an intracrevicular washing method. Samples were taken in the same way from a group of patients with gingivitis alone (GG). The periodontitis patients received non-surgical periodontal treatment and were re-evaluated 30 days later. We compared elastase and collagenase activities before and after treatment. The former activity was measured with a low-weight substrate (S-2484) and inhibited by alpha-1-antitrypsin. Matrix-metalloproteinase-8 (MMP-8) was measured with an ELISA and collagenolytic activity with fluorescein-conjugated collagen type I as substrate. RESULTS: All clinical parameters showed a significant improvement after treatment (p<0.05) which was accompanied by a significant reduction in the values of total elastase activity, free elastase, MPP-8 and collagenolytic activity in both GP and PP sites (p<0.05). However, the latter sites continued to have higher levels of MMP-8 and collagenolytic activity than the former ones after treatment. The free elastase activity and the proportion of free elastase in GP and PP samples after treatment remained higher than in untreated GG samples. CONCLUSION: This study shows that the clinical improvements after non-surgical treatment are accompanied by reductions in protease and neutrophil activities.

Adult↗

Subgingival plaque microbiota in Saudi Arabians after use of miswak chewing stick and toothbrush.

BACKGROUND: The chewing stick, the miswak, is used in many developing countries as the traditional means for oral hygiene. It is prepared from the roots, twigs and stem of Salvadora persica or other alternative local plants. OBJECTIVES: To compare the effects of the chewing stick miswak (from S. persica) and toothbrush on subgingival plaque microflora among Saudi Arabian individuals. Further, to investigate whether components extracted from S. persica may interfere with the subgingival plaque micro-organisms. MATERIAL AND METHODS: Fifteen healthy Saudi Arabian male volunteers aged 21-36 years were included in a single-blind, randomized cross-over study. The participants were taught how to use each device properly. Plaque sampling for DNA test was performed at the baseline, 1 week after professional tooth cleaning, and after 3 weeks of either miswak or toothbrush use. Identification and quantification of microbial species were performed by the checkerboard method, using whole genomic, digoxigenin-labelled DNA probes. Inhibition zones around miswak were examined on agar plates with Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was analyzed in a bioassay with macrophages+/-extracts of miswak. RESULTS: Miswak and toothbrushing had a similar influence on the levels of the subgingival microbiota. However, A. actinomycetemcomitans was significantly more reduced by miswak (p<0.05) than by toothbrushing. These results were supported by our in vitro results which, indicated that extracts from S. persica might interfere with the growth and leukotoxicity of A. actinomycetemcomitans. CONCLUSIONS: In contrast to toothbrush use, miswak use significantly reduced the amount of A. actinomycetemcomitans in the subgingival plaque.

Adult↗

Evaluation of various attenuation corrections in lung SPECT in healthy subjects.

The effect of increasingly more sophisticated attenuation correction methods on image homogeneity has been studied in seven healthy subjects. The subjects underwent computed tomography (CT), single photon emission computed tomography (SPECT) and transmission computed tomography (TCT) of the thorax region in the supine position. Density maps were obtained from the CT and TCT studies. Attenuation corrections were performed using five different methods: (1) uniform correction using only the body contour; (2) TCT based corrections using the average lung density; (3) TCT based corrections using the pixel density; (4) CT based corrections using average lung density; and (5) CT based corrections using the pixel density. The isolated attenuation effects were assessed on quotient images generated by the division of images obtained using various attenuation correction methods divided by the non-uniform attenuation correction based on CT pixel density (reference method). The homogeneity was calculated as the coefficient of variation of the quotient images (CV(att)), showing the isolated attenuation effects. Values of CV(att) were on average 12.8% without attenuation correction, 10.7% with the uniform correction, 8.1% using TCT map using the average lung density value and 4.8% using CT and average lung density corrections. There are considerable inhomogeneities in lung SPECT slices due to the attenuation effect. After attenuation correction the remaining inhomogeneity is considerable and cannot be explained by statistical noise and camera non-uniformity alone.

Adult↗

Clostridium difficile: prevalence in horses and environment, and antimicrobial susceptibility.

REASONS FOR PERFORMING STUDY: Clostridium difficile has been associated with acute colitis in mature horses. OBJECTIVES: To survey C. difficile colonisation of the alimentary tract with age, occurrence of diarrhoea and history of antibiotic therapy; and to study the occurrence and survival of C. difficile in the environment and antimicrobial susceptibility of isolated strains. METHODS: A total of 777 horses of different breeds, age and sex were studied. Further, 598 soil samples and 434 indoor surface samples were examined. Antimicrobial susceptibility of 52 strains was investigated by Etest for 10 antibiotics. RESULTS: In horses that developed acute colitis during antibiotic treatment, 18 of 43 (42%) were positive to C. difficile culture and 12 of these (28%) were positive in the cytotoxin B test. Furthermore, C. difficile was isolated from a small number of diarrhoeic mature horses (4 of 72 [6%]) with no history of antibiotic treatment, but not from 273 healthy mature horses examined or 65 horses with colic. An interesting new finding was that, in normal healthy foals age < 14 days, C. difficile was isolated from 1/3 of foals (16 of 56 [29%]). All older foals (170) except one were negative. Seven of 16 (44%) nondiarrhoeic foals treated with erythromycin or gentamicin in combination with rifampicin were also excretors of C. difficile. On studfarms, 14 of 132 (11%) outdoor soil samples were positive for C. difficile in culture, whereas only 2 of 220 (1%) soil samples from farms with mature horses were positive for C. difficile (P = < 0.001). By PCR, it was demonstrated that strains from the environment and healthy foals can serve as a potential reservoir of toxigenic C. difficile. The experimental study conducted here found that C. difficile survived in nature and indoors for at least 4 years in inoculated equine faeces. The susceptibility of 52 strains was investigated for 10 antibiotics and all were susceptible to metronidazole (MIC < or = 4 mg/l) and vancomycin (MIC < or = 2 mg/l). CONCLUSIONS: C. difficile is associated with acute colitis in mature horses, following antibiotic treatment. Furthermore, C. difficile was isolated from 1 in 3 normal healthy foals age < 14 days. POTENTIAL RELEVANCE: Strains from healthy foals and the environment can serve as a potential reservoir of toxigenic C. difficile.

Acute Disease↗

Oral health and cardiovascular disease in Sweden.

OBJECTIVE: The purpose of the present study was to assess the relation between dental health and cardiovascular disease in an adult Swedish population. MATERIAL AND METHOD: A questionnaire was sent to 4811 randomly selected Swedes. It contained 52 questions about dental care habits, oral health, cardiovascular disease and their socio-economic situation. Odd ratios for all cardiovascular diseases (CVD) and the subgroup myocardial infarction, stroke and high blood pressure were calculated with a logistic regression model adjusted for age, gender, smoking, income, civil status and education. These ratios were calculated for subjects > or =41 years since few people suffer from CVD before this. RESULTS: The national questionnaire was answered by 2839 (59%) people between 20-84 years of age and, of them, 1577 were 41 years of age or more. We found a significant association between self-reported bleeding gums (odds ratio 1.60, p=0.0017), presence of dentures (odds ratio 1.57, p=0.0076) and known CVD, which has also been reported in international studies. However, no association between loose teeth, deep pockets and known CVD was detected. CONCLUSION: The results indicate that oral health and, especially gingival inflammation is associated with CVD.

Adult↗

Quantitative assessment of apoptotic and proliferative gingival keratinocytes in oral and sulcular epithelium in patients with gingivitis and periodontitis.

BACKGROUND: Periodontal disease is caused by a chronic infection inducing an inflammatory reaction that leads to a breakdown of tooth-supporting tissue. The maintenance of an equilibrium between the host defence and microorganisms in the sulcus is essential to preserve health. All multicellular organisms have mechanisms for killing their own cells, and use physiological cell death for defence, development, homeostasis and ageing. Apoptosis and proliferation are very important phenomena in regulating this and a disturbance is often associated with disease e.g. cancer, AIDS, Alzheimer's disease, rheumatoid arthritis. OBJECTIVE: The aim of this study was to determine whether the number of apoptotic and proliferative gingival keratinocytes differed between patients with gingivitis and those with periodontitis. MATERIAL AND METHODS: The distribution of neutrophil elastase, PCNA/cyclin, DNA fragmentation (apoptosis) and p53 was determined with immunocytochemical techniques. We used paraffin-embedded sections from gingival biopsies and did quantitative analyses. RESULTS AND CONCLUSION: These showed that 5-12% of the keratinocytes in the basal layers of the epithelium proliferated in the two groups. Fewer apoptotic cells were seen in the oral epithelium than in the sulcus in all subjects in both groups. Only in the most apical part of the sulcus, close to the junctional epithelium, did the number of apoptotic keratinocytes exceed the proliferative ones in patients with periodontitis.

Adult↗

Role of the glutamyl alpha-carboxylate of the substrate glutathione in the catalytic mechanism of human glutathione transferase A1-1.

The Glu alpha-carboxylate of glutathione contributes to the catalytic function of the glutathione transferases. The catalytic efficiency of human glutathione transferase A1-1 (GST A1-1) in the conjugation reaction with 1-chloro-2,4-dinitrobenzene is reduced 15 000-fold if the decarboxylated analogue of glutathione, dGSH (GABA-Cys-Gly), is used as an alternative thiol substrate. The decrease is partially due to an inability of the enzyme to promote ionization of dGSH. The pK(a) value of the thiol group of the natural substrate glutathione decreases from 9.2 to 6.7 upon binding to GST A1-1. However, the lack of the Glu alpha-carboxylate in dGSH raised the pK(a) value of the thiol in the enzymatic reaction to that of the nonenzymatic reaction. Furthermore, K(M)(dGSH) was 100-fold higher than K(M)(GSH). The active-site residue Thr68 forms a hydrogen bond to the Glu alpha-carboxylate of glutathione. Introduction of a carboxylate into GST A1-1 by a T68E mutation increased the catalytic efficiency with dGSH 10-fold and reduced the pK(a) value of the active site bound dGSH by approximately 1 pH unit. The altered pK(a) value is consistent with a catalytic mechanism where the carboxylate contributes to ionization of the glutathione thiol group. With Delta(5)-androstene-3,17-dione as substrate the efficiency of the enzyme is decreased 24 000-fold while with 4-nitrocinnamaldehyde (NCA) the decrease is less than 150-fold. In the latter reaction NCA accepts a proton and, unlike the other reactions studied, may not be dependent on the Glu alpha-carboxylate for deprotonation of the thiol group. An additional function of the Glu alpha-carboxylate may be productive orientation of glutathione within the active site.

Binding Sites↗

Quantitative analysis of inhomogeneity in ventilation SPET.

The aim of this study was to evaluate a method for quantification of inhomogeneity in ventilation single-photon emission tomography (SPET). Nine emphysematous patients, nine life-long non-smokers and nine smokers were included in the study. The SPET investigation was performed after 50 MBq (99m)Tc-Technegas had been inhaled by each subject in the supine position. A single-head gamma camera, equipped with a general-purpose parallel-hole collimator using 64 projections (20 s each) over 360 degrees, was used. Data were acquired in 128x128 matrices. Attenuation correction was applied based upon computed tomography (CT) density maps. Lung regions of interest were delineated manually on CT images and then positioned on SPET images. Several attenuation-corrected transaxial SPET slices (thickness 1 cm, spacing 3.5 cm) were reconstructed. Each SPET slice was divided into several 2x2x1 cm(3) elements. Inhomogeneity was assessed by the coefficient of variation (CV) of the pixel counts within these elements (micro-level) and the CV of the total counts of the elements (macro-level). Micro-level CVs in non-smokers varied between 1% and 41%, whereas they were dispersed over a wide range (1%-600%) in emphysematous patients. In seven smokers, the frequency distribution of micro-level CVs was within the normal range, whereas in the other two smokers the values were between the normal range and the range in emphysematous patients. The pooled mean values of micro-level CVs and macro-level CVs in each subject clearly separated the patients from the others. Parametric images of micro-level CV indicated the localisation and severity of ventilation inhomogeneity. We conclude that the present method enables quantification and localisation of regional inhomogeneity in ventilation SPET images.

Adult↗

Human glutathione transferase A1-1 demonstrates both half-of-the-sites and all-of-the-sites reactivity.

A study of the kinetics of a heterodimeric variant of glutathione transferase (GST) A1-1 has led to the conclusion that, although the wild-type enzyme displays all-of-the-sites reactivity in nucleophilic aromatic substitution reactions, it demonstrates half-of-the-sites reactivity in addition reactions. The heterodimer, designed to be essentially catalytically inactive in one subunit due to a single point mutation (D101K), and the two parental homodimers were analyzed with seven different substrates, exemplifying three types of reactions catalyzed by glutathione transferases (nucleophilic aromatic substitution, addition, and double-bond isomerization reactions). Stopped-flow kinetic results suggested that the wild-type GST A1-1 behaved with half-of-the-sites reactivity in a nucleophilic aromatic substitution reaction, but steady-state kinetic analyses of the GST A1-D101K heterodimer revealed that this was presumably due to changes to the extinction coefficient of the enzyme-bound product. In contrast, steady-state kinetic analysis of the heterodimer with three different substrates of addition reactions provided evidence that the wild-type enzyme displayed half-of-the-sites reactivity in association with these reactions. The half-of-the-sites reactivity was shown not to be dependent on substrate size, the level of saturation of the enzyme with glutathione, or relative catalytic rate.

Base Sequence↗

Can dose-response models predict reliable normal tissue complication probabilities in radical radiotherapy of urinary bladder cancer? The impact of alternative radiation tolerance models and parameters.

PURPOSE: To analyze the consequences of selecting alternative normal tissue complication probability (NTCP) models and parameters for evaluation of radiotherapy of urinary bladder cancer. METHODS AND MATERIALS: Treatment plans of 24 bladder cancer patients referred to radical 4-field conformal radiotherapy were analyzed. Small intestinal and rectal NTCPs were determined using both the probit and relative seriality models with several sets of published radiation tolerance parameters. Various combinations of NTCP models and parameters were applied to find the prescription dose in individual patients as well as to estimate the benefit of the conformal radiotherapy setup. RESULTS: Different risk estimates were predicted from the two NTCP models, even when the same clinical radiation tolerance doses were fitted into the two models. The demonstrated variability translated into significant deviations (7-10 Gy) in the recommended prescription doses. Even if it was possible to discriminate between a 2-field plan and the 4-field conformal setup using a given complication model and set of tolerance parameters, the estimated benefit of the conformal treatment in terms of permitted dose escalation varied with as much as 10-12 Gy between the different NTCP models/parameters used. CONCLUSION: Different NTCP models and tolerance parameters might propose different answers to important clinical questions in radiotherapy treatment of bladder cancer, such as dose prescription and scoring of rival treatment plans. We therefore recommend that the variability caused by tolerance parameter uncertainty and model selection should be taken into account in dose-response modeling of radiotherapy treatment.

Aged↗

Partially wedged beams improve radiotherapy treatment of urinary bladder cancer.

BACKGROUND AND PURPOSE: Partially wedged beams (PWBs) having wedge in one part of the field only, can be shaped using dynamic jaw intensity modulation. The possible clinical benefit of PWBs was tested in treatment plans for muscle-infiltrating bladder cancer. MATERIAL AND METHODS: Three-dimensional treatment plans for 25 bladder cancer patients were analyzed. The originally prescribed standard conformal four-field box technique, which includes the use of lateral ordinary wedge beams, was compared to a modified conformal treatment using customized lateral PWBs. In these modified treatment plans, only the anterior parts of the two lateral beams had a wedge. To analyze the potential clinical benefit of treatment with PWBs, treatment plans were scored and compared using both physical parameters and biological dose response models. One tumour control probability model and two normal tissue complication probability (NTCP) models were applied. Different parameters for normal tissue radiation tolerance presented in the literature were used. RESULTS: By PWBs the dose homogeneity throughout the target volume was improved for all patients, reducing the average relative standard deviation of the target dose distribution from 2.3 to 1.8%. A consistent reduction in the maximum doses to surrounding normal tissue volumes was also found. The most notable improvement was demonstrated in the rectum where the volume receiving more than the prescribed tumour dose was halved. Treatment with PWBs would permit a target dose escalation of 2-6 Gy in several of the patients analyzed, without increasing the overall risk for complications. The number of patients suitable for dose escalation ranged from 3 to 15, depending on whether support from all or only one of the five applied NTCP model/parameter combinations were required in each case to recommend dose escalation. CONCLUSION: PWBs represent a simple dose conformation tool that may allow radiation dose escalation in the treatment of muscle-infiltrating urinary bladder tumours.

Adult↗

Neutrophil-related host response in hidradenitis suppurativa: a pilot study in patients with inactive disease.

Host-defence defects in hidradenitis suppurativa patients have been suspected, but not proven. Activated neutrophils can destroy the surrounding tissues by a release of reactive oxygen species and active proteases. Peripheral neutrophils from 15 female patients (mean age 46, range 27-57 years) in an inactive state of their hidradenitis suppurativa, were studied and compared with 15 age-matched healthy female controls. There were no significant differences between patients and controls in the assessments of intracellular elastase activity, total content of antigenic elastase or release of elastase. Furthermore, no differences were found in total content and membrane expression of the receptors measured. The generation of free oxygen radicals, after stimulation with the protein kinase C activator phorbol myristate acetate, was significantly higher in the patients than in the controls, while there was no difference after Fc-receptor-mediated stimulation. Dysfunctional neutrophils might be involved in the pathogenesis of hidradenitis suppurativa, but the findings should be interpreted with caution because of the small number of observed cases.

Adult↗

Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes.

We assessed the prevalence of families with both type 1 and type 2 diabetes in Finland; and we studied, in patients with type 2 diabetes, the association between a family history of type 1 diabetes, glutamic acid decarboxylase (GAD) antibodies (GADab), and type 1 diabetes-associated human leukocyte antigen (HLA) DQB1-genotypes. Further, in mixed type 1/type 2 diabetes families, we investigated whether sharing an HLA haplotype with a family member with type 1 diabetes influenced the manifestation of type 2 diabetes. Among 695 families ascertained through the presence of more than 1 patient with type 2 diabetes, 100 (14%) also had members with type 1 diabetes. Type 2 diabetic patients from the mixed families had, more often, GADab (18% vs. 8%, P < 0.0001) and DQB1*0302/X genotype (25% vs. 12%, P = 0.005) than patients from families with only type 2 diabetes; but they had a lower frequency of DQB1*02/0302 genotype, compared with adult-onset type 1 patients (4% vs. 27%, P < 0.0001). In the mixed families, the insulin response to oral glucose load was impaired in patients who had HLA class II risk haplotypes, either DR3(17)-DQA1*0501-DQB1*02 or DR4*0401/4-DQA1*0301-DQB1*0302, compared with patients without such haplotypes (P = 0.016). This finding was independent of the presence of GADab. We conclude that type 1 and type 2 diabetes cluster in the same families. A shared genetic background with a patient with type 1 diabetes predisposes type 2 diabetic patients both to autoantibody positivity and, irrespective of antibody positivity, to impaired insulin secretion. The findings support a possible genetic interaction between type 1 and type 2 diabetes mediated by the HLA locus.

Autoantibodies↗