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- Lindqvist, Maria, et al.
(författare)
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Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.
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| 3. |
- Lindqvist, Johan, 1985-
(författare)
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Cellular and Molecular Mechanisms Underlying Congenital Myopathy-related Weakness
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Congenital myopathies are a rare and heterogeneous group of diseases. They are primarily characterised by skeletal muscle weakness and disease-specific pathological features. They harshly limit ordinary life and in severe cases, these myopathies are associated with early death of the affected individuals. The congenital myopathies investigated in this thesis are nemaline myopathy and myofibrillar myopathy. These diseases are usually caused by missense mutations in genes encoding myofibrillar proteins, but the exact mechanisms by which the point mutations in these proteins cause the overall weakness remain mysterious. Hence, in this thesis two different nemaline myopathy-causing actin mutations and one myofibrillar myopathy-causing myosin-mutation found in both human patients and mouse models were used to investigate the cascades of molecular and cellular events leading to weakness.I performed a broad range of functional and structural experiments including skinned muscle fibre mechanics, small-angle X-ray scattering as well as immunoblotting and histochemical techniques. Interestingly, according to my results, point mutations in myosin and actin differently modify myosin binding to actin, cross-bridge formation and muscle fibre force production revealing divergent mechanisms, that is, gain versus loss of function (papers I, II and IV). In addition, one point mutation in actin appears to have muscle-specific effects. The presence of that mutant protein in respiratory muscles, i.e. diaphragm, has indeed more damaging consequences on myofibrillar structure than in limb muscles complexifying the pathophysiological mechanisms (paper II).As numerous atrophic muscle fibres can be seen in congenital myopathies, I also considered this phenomenon as a contributing factor to weakness and characterised the underlying causes in presence of one actin mutation. My results highlighted a direct muscle-specific up-regulation of the ubiquitin-proteasome system (paper III).All together, my research work demonstrates that mutation- and muscle-specific mechanisms trigger the muscle weakness in congenital myopathies. This gives important insights into the pathophysiology of congenital myopathies and will undoubtedly help in designing future therapies.
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| 4. |
- Lindqvist, Ulla, et al.
(författare)
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[11C]Hyaluronan uptake with positron emission tomography in liver disease
- 2000
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 30:7, s. 600-607
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundA hyaluronan-loading test has been developed for assessment of hyaluronan kinetics and applied in patients with liver and joint diseases. This test describes the metabolic process of hyaluronan but cannot define the specific contribution of different organs. A method for labelling of hyaluronan with the short-lived positron-emitting radionuclide 11C has been published and in this study applied in healthy subjects and liver diseases.Materials and methodsPositron emission tomography (PET) was used for the regional assessment and quantification of [11C]hyaluronan uptake in three healthy subjects, four patients with alcoholic liver cirrhosis, one with alcoholic hepatitis and one with liver steatosis. After intravenous administration of 60 MBq of 11C-labelled hyaluronan, a 55-min PET scan was performed over the liver and plasma radioactivity was analysed. Rate constants describing the transport of the [11C]hyaluronan tracer from plasma to the liver were calculated.ResultsHigh uptake was observed in the liver combined with a rapid elimination of tracer from plasma. The liver uptake rate (k1) was significantly lower in patients (0.018 min−1) than in healthy subjects (0.043 min−1, P = 0.002). The rate constants seem to be related to the severity of the disease as defined by the Child–Pugh score.ConclusionsThe study suggests that PET with [11C]hyaluronan could be an accurate method by which to assess liver dysfunction, in conditions where endothelial cell function is impaired. The possibility of quantification over extended portions of the body also opens up possibilities to explore regional differences in liver function and to assess other elimination routes of hyaluronan.
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| 6. |
- Gustafsson, Ulf, 1976-, et al.
(författare)
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The effect of acute myocardial ischemia on the rotation axis of the left ventricle
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: We have developed a method to assess the axis around which the left ventricle (LV) rotates. The aim was to assess the effect of acute regional ischemia on the otation axis. Method: Mid‐LAD occlusion was induced in six anesthetised pigs and echocardiographic images were recorded at baseline and after LAD occlusion. The rotation axis was calculated at three different levels of the LV throughout the cardiac cycle. Results: The direction of the rotation axis was significantly changed (p<0.01) after LAD occlusion, being directed towards the ischemic area. AV‐plane displacement was significantly reduced (p<0.05) during ischemia. No significant difference in twist or otation amplitudes was found. Conclusion: This new method of assessing rotational function seems as sensitive as AV‐plane displacement and superior to traditional rotation and twist parameters in detecting dysfunction in acute ischemic myocardium. The rotation axis method has the advantage of potentially identifying areas with dysfunction.
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| 7. |
- Gustafsson, Ulf, 1976-, et al.
(författare)
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The rotation axis of the left ventricle : a new concept derived from ultrasound data in healthy individuals
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The axis around which the left ventricle (LV) rotates has never previously been described. The aim was to develop a method to calculate the spatial motion of the rotation axis throughout the cardiac cycle. Method: By constructing a model of the LV, based on dimensions and rotation values at the basal, mid ventricular and apical levels, a rotation axis could be calculated at each level in 39 healthy subjects. The transition plane, defined as the level without rotation, where basal and apical rotation meet was also calculated. Results: The rotation axis was not congruent to the longitudinal axis of the LV at any time point. A significant and specific mean direction for each of the rotation axes for the majority of the tested time points displayed a physiological pattern. Conclusion: This new method introduces a new concept in cardiac function and provides further insight into the complexity of LV mechanics.
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| 8. |
- Gustafsson, Ulf, 1976-
(författare)
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Ventricular rotation and the rotation axis : a new concept in cardiac function
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.
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| 9. |
- Hossain, Akter, 1967-
(författare)
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Studies on Redox-proteins and Cytokines in inflammation and Cancer
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The redox state in the cell plays a major role in determining vital functions and its major imbalance can lead to severe cell injury or death. Redox active proteins and cytokines involved in this process includes thioredoxin (Trx), protein disulfide isomerase (PDI), and tumor necrosis factor (TNF) superfamilies. Trx is a multipotent protein and key regulator of cellular redox balance operating in synergy with Trx reductase and NADPH (the Trx system). Trx has gene regulatory activity of several transcription factors. It also controls in a fascinating way redox-sensitive “on-off” decisions for apoptotic or hypertrophic pathways. Trx protects against H2O2 and TNFmediated cytotoxicity, a pathway in which TNF receptor-binding generates ROS. TNF is an autocrine growth factor and survival factor in vitro and in vivo for B-type of chronic lymphocytic leukemia (B-CLL) cells. The overall aim of this study was to investigate the importance of redox active proteins and cytokines in inflammation and cancer. We focused on: i) the role of Trx, TrxR, and selenium in carcinogenesis and in resistant cancer cells. ii) the importance of Trx in cancer cells and the redox regulation of TNF and its receptors TNFR1 and TNFR2. iii) the potential role of Trx as a key regulator in cellular redox balance, in the pathogenesis of cardiac dysfunction; its relationship to stress response parameters. iv) whether unmutated CLL (UCLL) responses to PKC and ROS pathways were different from mutated CLL (M-CLL) responses.Our results demonstrate pronounced selective selenium-mediated apoptosis in therapy resistant cells and suggest that redox regulation through the Trx system is an important target for cancer therapy. Trx was strikingly elevated in heart failure cases compared with controls signifying an adaptive stress response that is higher the more severe the disease. TNF autocrine release was redox modulated and the TNF receptors interacted at the cell surface membrane with the redox-active PDI, which excerted a stringent redox-control of the TNFR signaling. The proliferative response as well as increase of autocrine TNF and Trx were higher in U-CLL than in M-CLL.The overall conclusion of the four papers included in this thesis is that redox-active proteins and cytokines plays an important role in control and regulation of cancer and inflammation. Furthermore, redox regulation via thioredoxin by selenium, may offer novel treatment possibilities for resistant tumors disease.
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| 10. |
- Koldestam, Maria, 1968-
(författare)
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MILO - A Conceptual Learning Model Grounded in a Hermeneutical and a Caritative Caring Perspective : Development and Evaluation
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overall aim was to develop and evaluate a conceptual learning model grounded in a caritative caring perspective aimed to facilitate undergraduate nursing students’ learning during clinical practice.Methods: This thesis comprises four studies with a descriptive explorative design overall. In the inductively applied research, different designs using both qualitative and quantitative methods, were used. Studies I–III used qualitative methods; data for study I were collected using the Delphi method and analysed using qualitative data analysis. In study II, data were collected using focus group interviews and analysed using latent content analysis. In study III, data were collected using individual interviews and analysed using a phenomenographic approach. Study IV used quantitative methods and data were collected using a questionnaire and analysed using statistical methods.Results: Study I resulted in a conceptual learning model grounded in hermeneutics and a caritative caring perspective. The Model for Improvement in Learning Outcomes (MILO) encompasses eight concepts: four intrapersonal, i.e. the students’ own characteristics, reflecting understanding, and four contextual concepts, i.e. environmental concepts, reflecting structure. Study II showed that students’ learning is facilitated as a result of natural actions and elements that occur in daily life, integrating natural caring with professional caring. Studies III and IV showed that students’ learning was a gain in knowledge and understanding of supportive elements for learning and the perspective of the patients, and a gain in engagement and dedication. Study IV also showed that the intrapersonal concepts were valued more than the contextual concepts in the three different semesters studied. The use of the applications was valued more at the start of the students’ education. Some of the concepts and their applications had not been used in accordance with MILO’s implementation in the region involved.Conclusions: The fundamentals needed to become a professional caring nurse include having compassion and competence. Undergraduate nursing students’ learning during clinical practice needs to be facilitated by a theoretical foundation establishing an ethical bearing, by knowledge and understanding of one self and of the patient as a whole, and by challenged learning using a diversity of tools to achieve the intended outcome of better health and well-being for the patient.
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