| 1. |
- Vessby, Johan, 1972-
(author)
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Studies of ulcerative colitis with concomitant primary sclerosing cholangitis : Beyond the clinical phenotype
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Inflammatory bowel disease (IBD) is a group of chronically relapsing immune-related disorders, engaging the gastrointestinal tract. Symptoms vary depending on inflammatory phenotype, but may include diarrhoea, bowel pain and weight loss. The two most common entities are Crohn's disease and ulcerative colitis (UC). A minority of IBD patients, particularly UC, is concomitantly affected by primary sclerosing cholangitis (PSC) – an inflammatory bile duct disease with dismal prognosis. IBD with associated PSC has distinct clinical features, and is regarded a unique IBD phenotype (PSC-IBD or PSC-UC). These features include higher rates of pancolitis, a milder clinical course, and an unexplained increased risk of colorectal neoplasia.This thesis aimed to compare immunological conditions in PSC-UC and UC, but also to search for molecular differences, potentially facilitating PSC-UC diagnosis.In paper I and II, we compared eosinophil and lymphocyte activation and regulation. PSC-UC had down-regulated mucosal eosinophil activity, during both flare and remission. Compared with UC, PSC-UC had a dampened, and less Th2 dominated mucosal immune response. This was evident by a low quote of CRTH2/CXCR3 CD4+ cells and a cytokine milieu with no upregulated Th2 cytokines. In contrast, PSC-UC had highly up-regulated cytokines in peripheral blood. Among these, sCD40 stood out as being most important for inter-group separation according to multivariate analysis.In paper III, we gave a detailed description of colonic tissue factor (TF) expression. We found discrepancies in TF depending on UC subtype and inflammatory status, where inflammation- associated TF up-regulation was detected in UC only. Also, we identified stromal TF deposition as a sensitive indicator of acute colitis.In paper IV, PSC-UC and UC intestinal proteomes were compared using LC-MS/MS. After detecting more than 7200 unique proteins in the discovery step, the top-five most distinctive findings were chosen for verification. Of these, AGPAT1 was verified, being significantly higher in PSC-UC. Despite phenotypical differences, the overall colonic proteome comparison showed high degree of concordance.In summary, this thesis demonstrates distinct immunological and molecular properties in PSC-UC, implying phenotypical features beyond clinical observations. Moreover, serum sCD40 and colonic AGPAT1 are suggested possible PSC-UC biomarkers.
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| 2. |
- Kämpe, Mary, 1956-
(author)
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Eosinophil Inflammation in Allergic Disease : Clinical and experimental studies in allergic asthma and allergic rhinitis
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Allergic diseases are chronic inflammatory conditions, characterised by eosinophil inflammation systemically and in target organs, where cytotoxic granule proteins are responsible for tissue injury. Allergic rhinitis is known to be a risk factor for the development of asthma, yet not all with rhinitis develop asthma. The overall aim was to investigate the involvement of eosinophils in allergic rhinitis and allergic asthma in vivo and in experimental settings, with a focus on differences between rhinitis and asthma. Birch pollen allergy was used as a model and patients were studied during pollen season and after nasal and bronchial allergen challenge. During pollen season and at baseline, allergic rhinitis and allergic asthma had the same degree of systemic eosinophil inflammation. Despite this, impairment in lung function during season and increased bronchial responsiveness at baseline were more common in the asthmatics. Systemic inflammation was more pronounced after seasonal exposure than after experimental challenge. Allergic rhinitis and allergic asthma had the same degree of eosinophil airway inflammation after bronchial challenge, but only the asthmatics had increased bronchial responsiveness measured as PD20 for birch allergen. Allergen primed eosinophils were investigated in vitro for C3b-induced degranulation after seasonal and experimental challenge. The released amount of eosinophil granule proteins was within the same range for all three allergen challenge models with just minor differences in propensity for degranulation between rhinitics and asthmatics. Signalling through PI3K for degranulation was studied with the specific inhibitor Wortmannin. PI3K signalling for eosinophil degranulation was clearly involved in allergic rhinitis and allergic asthma irrespective of the model for allergen exposure. Asthmatics demonstrated less inhibition of degranulation through PI3K during pollen season, indicating that other pathways contribute to eosinophil degranulation in allergic asthmatics. Conclusion: Allergic rhinitis and allergic asthma present with the same degree of systemic and local eosinophil inflammation. The eosinophils are primed for degranulation equally and follow the same pathway through PI3K for degranulation. Our data indicates that eosinophil inflammation per se is not sufficient for the development of asthma.
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| 3. |
- Ahlgren, Katrin, 1970-
(author)
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Narrativa identiteter och levande metaforer i ett andraspråksperspektiv
- 2014
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Doctoral thesis (other academic/artistic)abstract
- This thesis consists of two separate yet connected studies which investigate how some adult second language speakers of Swedish with various backgrounds reflect on their experiences of language use. The studies are based on the same empirical data, which consists of questionnaires, diaries, essays and observations, but primarily of conversations conducted with a time interval of six years. This data is analysed from a theoretical framework based on Paul Ricœur’s ideas of interpretation, narrative analysis and identity creation, which recur as a leitmotif throughout the thesis.In the first study, data from three second language speakers are analysed by means of the concept of narrative identity, shedding light on the interplay between a static and a dynamic identity. The result is presented in the form of life narratives, which are commented on in relation to those strategies the participants express in relation to their second language use. The analysis shows a development over time moving from defiance to acceptance, from avoidance to flexibility and from planning to simplification. Adult language learning stands out as an arduous and time-consuming process with major consequences for the learner’s ego, a conclusion confirmed and clarified in the metaphor analysis of the second study in which language learning is related to hard work, a constant struggle and a long and strenuous journey. Here it also becomes evident that the participants equate language learning and language use to physical exertion and challenge as well as to individual achievement. This becomes particularly clear in the linked chains of metaphors in which language use is compared with skiing down the steepest slopes or appearing on stage.The participants in both studies are quoted by means of an ethnopoetic method which aims to bring out the creative aspects of their language use and to give second language speakers a voice – a voice which does not need to be corrected and gives the narratives a new dimension.
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| 4. |
- Lampinen, Maria, et al.
(author)
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High Serum sCD40 and a Distinct Colonic T Cell Profile in Ulcerative Colitis Associated With Primary Sclerosing Cholangitis
- 2019
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 13:3, s. 341-350
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Journal article (peer-reviewed)abstract
- Background and Aims: There is a strong association between primary sclerosing cholangitis [PSC] and ulcerative colitis [UC], but the immunological link between the two diseases is obscure. We compared serum cytokine profiles of patients with PSC-UC and UC, and investigated a number of selected cytokines in colonic biopsy samples. We also assessed the presence and activation of T cells in peripheral blood and colonic mucosa.Methods: Serum samples from 22 patients with PSC-UC, 28 patients with UC, and 19 controls were analysed by a proximity extension assay including 92 inflammatory cytokines. Biopsies from caecum, sigmoid colon, and rectum were collected from the same patients. Quantitative analysis for IFN-, IL-2, IL-4, IL-5, IL-13, IL-17A/ E/F, IL-21, IL-22, IL-23, and IL-27 was carried out on tissue homogenates. T cell phenotype was evaluated by flow cytometry.Results: By multivariate analysis we identified a cluster of serum cytokines with higher levels in PSC-UC, and sCD40 in particular was strongly associated with this patient group. In contrast, colonic cytokines were only modestly increased in PSC-UC, whereas several Th1-, Th2-, and Th17-associated cytokines were increased in UC. Patients with PSC-UC had increased colonic levels of CXCR3-positive CD8(+) T cells but fewer CD25-positive CD4(+) T cells. An increased CRTH2/CXCR3-quote indicated a predominance of Th-2 type CD4(+) T cells in UC patients.Conclusions: Our study reveals different cytokine profiles and T cell profiles in PSC-UC and UC, with higher systemic levels of cytokines in PSC-UC, and a more pronounced colonic inflammation in UC. Serum sCD40 could potentially be investigated as a marker for PSC in UC.
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| 5. |
- Sarstrand Marekovic, Anna-Maria, 1976-
(author)
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Från invandrarbyrå till flyktingmottagning : Fyrtio års arbete med invandrare och flyktingar på kommunal nivå
- 2011
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Doctoral thesis (other academic/artistic)abstract
- The dissertation investigates what happened when a new field – the incorporation of immigrants and refugees – was to be organized at the local level in Sweden. The result shows that the public authorities during the 40 year period that the study covers struggled with several questions, such as: how they should organize this, who should carry out the work, what should be done in practice, and towards which groups should it be directed? It is around these questions that the municipal work with immigrants and refugees revolved, without finding any clear and permanent answers. I analyze this in terms of four themes: responsibility, personnel and competence structure, direction of the work, and target group, which together constitute what I call the organizations’ ‘practices of incorporation’. The main aim with the dissertation is to illuminate and analyze how these practices have developed and changed from the mid 1960’s and approximately 40 years on. To accomplish this I have conducted a historical and comparative study of eight municipalities. The material comprises several different sources, from interviews with civil servants and participant observation, to archive material and secondary literature. My theoretical perspective is mainly drawn from the sociology of organizations, with a focus on the history of organizations.The analysis defines two roughly defined periods, the period of immigrant service bureaus (1965-1985) and the period of refugee reception centers (1985-2008). My study of the history of the organizations shows both the change of practice that has occurred and the stability that remains at the same time. It also shows that the transition to refugee reception centers made it necessary to redefine and renegotiate the practices of incorporation. During the first 20 years covered in this dissertation, the immigrant service bureaus developed into independent administrative agencies; they became institutionalized as organizations. The break occurred as soon as the new system for refugee reception was initiated in the mid-1980s, when the role of the social welfare offices increased considerably. In recent years there are signs that labor market units in the municipalities are strengthening their role in relation to the reception centers, but also that the social welfare offices ‘working under cover’ continue to have the main responsibility for reception centers. Criticism against the role of the social welfare offices is mostly based on the accusation that they tend to make immigrants and refugees into clients, dependent on subsidies and remaining outside the labour market. In sum, the introduction of municipal refugee reception centers ultimately led to the closing of practically all immigrant service bureaus during the 1990s. In some individual cases they have lived on, or had some of their functions included in the praxis of the refugee reception centers, but on the whole they became increasingly marginalized, and finally disappeared.
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| 6. |
- Stenberg, Marie, et al.
(author)
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Collaboration between first year undergraduate nursing students : A focused ethnographic study
- 2022
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In: Nurse Education in Practice. - : Elsevier. - 1471-5953 .- 1873-5223. ; 64
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Journal article (peer-reviewed)abstract
- AIM: The aim was to explore collaboration between first year undergraduate nursing students in a three-year bachelor program during clinical skills lab practices.BACKGROUND: The ability to collaborate is important in the nursing profession to ensure patient safety. Thus, efforts supporting nursing students with learning activities emphasizing this ability is crucial in nurse education as a preparation for the requirements of the nursing profession. Collaborative learning models are described as ways that support the students' interaction during education. However, collaboration between students has shown to have challenges such as negative competition and confrontations. This stresses the need to explore the collaboration between students to find ways to support the interaction.DESIGN: The study was conducted with a focused ethnographic approach.METHOD: Data were generated by participant observations during one semester, involving 70 h observation of 87 first year nursing students for 6 months and 24 training sessions in clinical skills lab practices. Two focus group discussions were used to elaborate students' views of collaboration and to provide an opportunity for follow up questions and interpretations from the observations. Field notes and focus group discussions were interpreted as one unit of analysis conducted with thematic network analysis. A global theme were synthesized from organizational and additional basic themes presenting the overall metaphor of the students' collaboration.RESULT: The global theme, Between adaptation and non-conformity, revealed a field of tension in the nursing students' collaboration. One the one hand, the global theme involved the students' ability to adopt to new knowledge and to being a nursing student in a clinical skills lab and to others' perspective. On the other hand, non-conformity creates a collaboration with less reflection between the students and non-synchronized and time-consuming laboratory work.CONCLUSION: Collaborative activities in nurse education fosters and challenges nursing students' collaboration required for clinical practices and later in the nursing profession. By the presented scaffolding efforts, nurse educators can arrange a learning environment that can support the collaboration between students and facilitate the transition into the profession.
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| 7. |
- Stenberg, Marie, et al.
(author)
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Supporting each other towards independence : A narrative analysis of first‐year nursing students' collaborative process
- 2024
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In: Nursing Inquiry. - : John Wiley & Sons. - 1320-7881 .- 1440-1800. ; 31:3
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Journal article (peer-reviewed)abstract
- Collaboration for nursing is a core competence and therefore educational interventions are essentials for collaborative skills. To identify such interventions, we carried out a study to understand nursing students' collaborative process. A narrative inquiry method was used to explore the collaborative process of first-year undergraduate nursing students. The analysis was conducted on field notes from 70 h of observation of 87 nursing students' collaboration during skills lab activities. It also included transcriptions of four focus group discussions with 11 students. The results are presented as a sequential process of (1) navigating in unfamiliar territory, (2) navigating together to cope, and (3) navigating together towards independency and the future nursing profession. We identified a transition from teacher-led assistance and guidance to student interdependency and reciprocal learning, ending with student-led assistance supporting independency. In line with Vygotsky's theory of zone of proximal development, different scaffolding interventions are needed depending on where the students are in the collaborative process.
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| 8. |
- Vessby, Johan, 1972-, et al.
(author)
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A two-step proteomic approach identifies candidate biomarker in ulcerative colitis with concomitant primary sclerosing cholangitis.
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Other publication (other academic/artistic)abstract
- Introduction: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC-UC or PSC-IBD) is today considered a unique IBD entity, including a more malignant disease course compared with classical UC. Biomarkers for identifying UC patients at risk of developing PSC is lacking, which may delay the onset of endoscopy surveillance. Mass spectrometric development has enabled the use of formalin-fixed paraffin embedded tissue (FFPE) for high resolution proteome analysis. In this study, we search for PSC-IBD proteomic fingerprints in FFPE by utilizing mass spectrometry.Methods: Protein was extracted out of FFPE colon archival samples from PSC-IBD (n=9), UC (n=7), and healthy controls (n=7). IBD-patients were all in clinical remission, without biologics or steroids, and all UC patients had a history of pancolitis. Samples were processed by the Multienzyme Digestion FASP and were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Proteins were quantified using the Total Protein Approach. Data was analysed using linear regression and in a multiple manner using random forest algorithms. Candidate findings were validated in a second cohort (n: PSC-IBD=16 UC=21) using the same proteomic technique. To make an over-all proteome comparison, we performed principal component analysis, as well as a meta-analysis for the most prominent findings.Results: In the exploratory proteomic step, 7279 unique proteins were detected. After statistical analysis including multiple testing, the top-5 proteins (CD47, LSM7, NDUFAF4, AGPAT1 and THEM192) were selected as candidate proteins. When validating these findings in a confirmatory cohort, AGPAT1 was verified (p=0.009). According to meta-analysis, AGPAT1 was also found to be the most distinctive protein between PSC-IBD and UC. The overall proteomic profiles in step 1 and step 2 (7706 proteins) confirmed small biologic variations between the IBD-groups.Conclusions: In this two-step proteomic study on remissive IBD, we were able to verify AGPAT1 as a colonic PSC-IBD biomarker. We found high overall proteome resemblance, in contrast to the phenotypical differences existing between PSC-IBD and UC. Our findings have possible implication in future PSC-IBD diagnostics, and adds further knowledge to the evasive PSC-IBD phenotype.
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| 9. |
- Vessby, Johan, 1972-, et al.
(author)
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AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis
- 2022
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In: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 13:5
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue.METHODS: Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry.RESULTS: In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC.DISCUSSION: We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance.
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| 10. |
- Vessby, Johan, 1972-, et al.
(author)
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Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis
- 2019
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In: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:4, s. 238-245
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Journal article (peer-reviewed)abstract
- Background: Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal cancer prognostication. Here we evaluate TF expression in an inflammatory bowel disease (IBD) cohort, with special focus on differences between UC and PSC-UC patients.Materials and methods: Colonic biopsies from UC (n = 23), PSC (n = 24), and healthy controls (n = 11) were stained for TF by immunohistochemistry. Mononuclear cell contribution to TF expression was verified using flow cytometry.Results: TF was distributed at three distinct colonic locations: in subepithelial pericryptal sheath cells, in mononuclear cells, and in the intestinal stroma. In contrast to UC-where inflammation was accompanied with TF up-regulation-PSC-UC activity remained low during inflammation. Stromal TF positivity was found exclusively in ongoing inflammation.Conclusion: Our study provides additional support for a divergent pathogenesis in PSC-UC, with an inflammatory environment that differs from classical UC. Stromal TF emerges as a new marker of colonic inflammation.
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