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1.
  • Schmidt, Manuela (författare)
  • Persons who frequently use psychiatric emergency services : perspectives on who they are, what their needs are and howthey are encountered by healthcare professionals
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The overall objective of the thesis was to describe who persons that frequently use psychiatric emergency services (PES) in Sweden are, to explore what needs they experience as well as how healthcare professionals working at PES view the needs of those persons and experience encounters with them.This thesis includes both quantitative (I, II) and qualitative (II, III, IV) research designs and applies a broad range of data collection methods, such as use of register data (I), use of survey data (II), individual interviews and focus group interviews (III, IV). Data were analysed with statistical tests (I, II) and with qualitative content analysis (II, III, IV).Study I is based on visits to PES during 2013–2015. A total of 27,282 persons made 67,031 visits. Of those 27,282 persons, 8.1% could be identified as frequent PES users, accounting for nearly two fifths of all visits. In Study II, 81 persons who frequently visited PES participated. The participants in Studies III and IV were healthcare professionals working at PES, such as assistant nurses, nurses with specialised education in psychiatry, and physicians. Nineteen healthcare professionals participated in individual interviews in both Study III and Study IV, and each of the studies was complemented with a focus group interview involving five and six professionals respectively.The findings of this thesis were as follows: persons who frequently use PES in Sweden are a small, yet highly heterogeneous group who make a disproportionately high number of visits and differ significantly from other PES visitors; persons who frequently use PES and healthcare professionals at PES are in agreement about the complex and intertwined need patterns of the patients that originate from problems in everyday living, acute psychiatric suffering, and insufficient care possibilities, and thus were found to suffer from illness, unfavourable life circumstances and inadequate care; healthcare professionals at PES experienced the encounter as consisting of caring, professional, and humane processes where persons who frequently use PES were seen as fellow human beings and as unique, and were treated with as much respect, kindness, humility, confirmation, and empowerment as possible; and that in order to have caring encounters with persons who frequently use PES, the healthcare professionals also needed to nurture the relationship with oneself and with colleagues. Those results were interpreted by means of person-centredness and in light of a recovery-oriented care approach. Even though the latter has received more acknowledgement and acceptance within psychiatric care in the last decade, it needs to be developed and implemented further in the Swedish psychiatric care context. 
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2.
  • Bruce, Barbro (författare)
  • Problems of language and communication in children; Identification and intervention
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis addresses identification and intervention of language and communication problems in children. The issue of identification is addressed in study I by investigating communicative ability in 18-month-old children, and in study II by exploring the prevalence of language and communication problems in children with complex problems, such as attention deficit hyperactivity disorder (ADHD). The issue of intervention is addressed in studies III and IV by analysing verbal interaction in conversations, in which one of the participants is a child with specific language impairment (SLI). Study III explores how dialogues between children with SLI and typically developing peers (TLD) representing the same age (age peers), and the same language level (language peers) respectively, differ with respect to responsiveness, assertiveness and reciprocity. Study IV investigates interactional style and elicitation strategies of speech/language pathologists (SLP) during intervention, and how these factors influence the child with SLI. The results from study I show that receptive skills and symbolic play at 18 months of age are significantly associated with language ability three years later. Study II, in which language skills in children with ADHD were explored, indicates that language ability plays an important role for all other aspects of children's development and behaviour, with the exception of motor skills. Use of language and language comprehension caused these children many more problems than structural aspects of language production. Furthermore, reading and writing problems were found to be very frequent. Study III shows that dialogues between children with SLI and TLD age peers are characterized by more responsiveness and topic coherence than dialogues between children with SLI and TLD language peers. However, the children with SLI were more assertive, i.e., introduced more topics, in dialogues with language peers. Study IV indicates that the children with SLI talked more and had a higher mean length of utterance (MLU) in the free conversational context, whereas the individually selected grammatical targets occurred more often in the training context. In the conversational context the SLPs linked, i.e., attended, more to the child's focus and gave more feedback, while in the training context the individually selected grammatical targets occurred more often and the children were more frequently asked to follow instructions. The results have important clinical implications. First; screening procedures at Child Health Care (CHC) centres should be recommended to focus on receptive language skills and play behaviour, and not only on size of vocabulary at 18 months of age. Second; language skills, in particular language comprehension, language use and literacy skills were found to cause children with ADHD problems, and should therefore be assessed. Third; it is of great value for children with SLI to be in mixed groups with peers representing different ages and language levels, and to avoid the risk of not being selected as playmates. Fourth; increased awareness of how interactional style and elicitation strategies influence the developing language skills in children with SLI can be used in intervention planning, depending on the goals of the specific intervention procedures for the individual child.
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3.
  • Deyhle Jr, Richard (författare)
  • Cross-modal Imaging in Lung Research: From µCT dosimetry to synchrotron phase contrast microtomography biomechanical insights in preclinical lung injury models
  • 2024
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Lung diseases continue to present a large burden to public health, especially in industrialized countries. For abetter understanding of the underlying patho-mechanisms in lung related diseases as well as for testing theefficacy of novel therapies, preclinical studies in animal models are indispensable. The significance of preclinical X-ray based micro-computed tomography (µCT) research lies in its ability to provide high-resolution, non-invasive lung imaging of small animals as the air inside the lung acts as a natural contrast and to image the lung parenchyma longitudinally to assess functional and morphological alterations and test efficacy of therapeutic interventions. This often requires requires imaging protocols that balance between sufficient image quality and clinically relevant radiation absorbed doses. A reproducible method for evaluation of absorbed radiation absorbed doses is desirable. Absorbed radiation absorbed doses were measured in a polymethyl methacrylate (PMMA) phantom using standard TLD and a novel type of OSLD made form household salt. Four imaging protocols from MILabs “xUHR-µCT” scanner were tested. A large discrepancy was observed from results compared to vendor-provided values. The results indicate a need for thorough empirical dose measurements prior to performing longitudinal studies. Four-dimensional imaging, allows for investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. It is of significant interest to have direct visualization and quantification of interstitial lung diseases at spatial resolutions beyond the capabilities of clinical and conventional absorption-based only CT. Thus far, the high intensity of synchrotron X-ray light sources offer a tool to investigate dynamic morphological and mechanistic features, enabling dynamic in-vivo microscopy. This investigation elucidates the direct effects of interventions targeting the pathophysiology of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) on the terminal airways and alveolar microstructure within intact lungs. In such conditions, the relationship between microscopic strain within the mechanics of the alveolar structure and the broader mechanical characteristics and viscoelastic properties of the lungs remains poorly understood. A time-resolved synchrotron phase-contrast micro-computed tomography imaging acquisition protocol based on the synchronization between the mechanical ventilation and the cardiac activity was used to resolve the lung parenchyma motion with an effective isotropic voxel size of 6 µm. Quantitative maps of microscopic local lung tissue strain within aerated lung alveolar tissue under protective mechanical ventilation in anesthetized rats were obtained. This approach was used to assess the effect of alterations in lung tissue biomechanics induced by lung injury at 7 days after single-dose, intratracheal bleomycin instillation in combination with short-term high-tidal volume (VT) mechanical ventilation. Overall, this work address the aspects of radiation exposure to in experimental imaging of small animals and lays a foundation for a more nuanced understanding of lung injury and mechanical ventilation. In the future, it may result in a more effective and less injurious respiratory support for patients with acute lung injury or chronic lung diseases.
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4.
  • Skog, Malin (författare)
  • Experiences of Screening for Postpartum Depression in Non-Native-Speaking Immigrant Mothers in the Swedish Child Health Services. Nurses’ and Mothers’ Perspectives.
  • 2018
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Postpartum depression (PPD) är ett globalt folkhälsoproblem. Mödrar som migrerar till ett annat land har en ökad risk att drabbas av PPD. Före-komsten av PPD bland utlandsfödda mödrar beräknas vara så hög som 20 procent, vilket nästan är dubbelt så hög som bland inhemsk västerländsk befolkning. Asylsökande och flyktingar är särskilt sårbara grupper som löper en ännu högre risk att drabbas, speciellt de som migrerat inom 10 år. Likaså de mödrar som inte talar språket i sitt nya hemland. PPD uppstår vanligtvis fyra till sex veckor efter förlossningen och kan ha långvariga traumatiska effekter inte bara på moderns egen hälsa utan även på hennes partners och framförallt på barnets hälsa och utveckling. Mot bakgrund av detta rekommenderar Socialstyrelsen att screening av nyblivna mödrar för PPD regelmässigt genomförs av sjuksköterskan i barnhälsovården (BHV) sex till åtta veckor efter förlossningen. Screeningen genomförs med hjälp av Edinburgh Postnatal Depression Scale (EPDS), som är en skala översatt och validerad till många olika språk. Skalan består av tio olika påståenden speciellt utvecklade för screening för PPD. Skalan används i kombination med ett samtal för att bedöma moderns psykiska mående. Vid screening av icke-svenskspråkiga mödrar instrueras sjuksköterskorna att använda ett översatt validerat formulär, ta hänsyn till moderns läs- och skrivkunnighet, tolkens arbete samt hur olika kulturella tolkningar av påståendena i skalan kan påverka resultatet. Screening av utlandsfödda mödrar har visat sig vara en utmanande arbetsuppgift för sjuksköterskorna. Tidigare forskning pekar på att dessa mödrar inte erbjuds delta i screening i samma omfattning som den inhemska befolkningen. Statistik visar också att invandrarmödrar i större utsträckning väljer att tacka nej till att delta i screening och likaså att bland de som deltar är det inte så många som förväntat som screenas ut i förhållande till den höga förekomsten av PPD i gruppen. Det övergripande syftet med studierna var att öka kunskapen om screening för PPD av icke-svenskspråkiga invandrarmödrar genom att belysa deras och BHV-sjuksköterskors erfarenheter. Ett ändamålsenligt urval användes vilket innebar att deltagare med erfaren¬¬heter av ämnet erbjöds delta i individuella intervjuer. Det insamlade text¬materialet analyserades med latent innehållsanalys med induktiv ansats. Det är en deskriptiv kvalitativ metod som syftar till att förutsättningslöst skapa kategorier och teman i avsikt att beskriva fenomenet för att öka förståelsen och kunskapen. Vid latent innehållsanalys tolkas även det underliggande budskapet i texten. Med syftet att belysa hur BHV-sjuksköterskor identifierar tecken på PPD hos icke-svenskspråkiga invandrarmödrar genomfördes 13 individuella inter-vjuer. Resultatet visade att en förutsättning för att kunna tolka den moderns sinnesstämning var etablerandet av en trans-kulturell vårdrelation som fördjupades. Sjuksköterskorna använde sig av kulturell kunskap för att uppfatta och tolka tecken på PPD i interaktionen med modern och i observationer av samspelet mellan mamma och barn, med tolken och anhöriga. Samtidigt orsakade bristande kulturell kompetens frustration hos sjuksköterskorna när de försökte anpassa screeningen efter de givna förutsättningarna och även när de försökte få mamman att öppna sig eller ta emot extern hjälp. Sjuksköterskorna förlitade sig även på sin intuition när de tolkade mammans sinnesstämning. För att få kunskap om hur icke-svenskspråkiga invandrarmödrar upplever att delta i screening för PPD i BHV intervjuades 13 med albanska, arabiska eller badinani som modersmål. Andra tolkar än de som användes i intervjusituationen lyssnade på ljudinspelningarna och validerade det utskrivna materialet. Resultatet visade att deltagandet i screeningen påminde mödrarna om deras brist på stöd i sin nuvarande livssituation, men sågs även som en möjlighet att erfara andra sätt att tänka kring psykisk ohälsa och nya källor till stöd. Kvalitén på relationen med sjuksköterskan var av betydelse för om modern valde att delta i screening och uppleva den som meningsfull. Innebörden av PPD var i allmänhet oklar, men möjligheten att delta i screening och därigenom bli behandlad som alla andra mödrar uppskattades. Kulturella föreställningar om psykisk ohälsa, negativa förväntningar kopplade till sitt upplevda värde som kvinna, skam över att inte vara tillräckligt tacksam för sitt nya liv och negativa upplevelser av interaktionen i samband med screeningen gjorde det utmanade för dem att tala om sitt mående. Studierna visar att screening för PPD av icke-svenskspråkiga invandrarmödrar kan underlättas av upprepad information om PPD både muntligt med hjälp av tolk, men även genom översatt material, ett förtroendefullt samtal med assistans av kvinnlig auktoriserad kontakttolk samt kunskap hos BHV-sjuksköterskor om olika utmaningar hos dessa mödrar för att kunna tala om psykiskt mående. Den förtrogenhetskunskap som erfarna BHV-sjuksköterskor besitter och använder sig av för att tolka icke-svenskspråkiga mödrars mående behöver ytterligare studeras. Det är också av intresse att undersöka om utbildning av BHV-sjuksköterskorna i kulturkänslig screening kan göra att screeningen av denna sårbara grupp av mödrar mer effektiv.
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5.
  • Lamei, Sepideh (författare)
  • The effect of honeybee-­specific lactic acid bacteria on american foulbrood disease of honeybees
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The honeybee, Apis mellifera, is one of the most economically important pollinators and highly valued for its honey and wax production. Managed honeybees occupy an increasingly critical role in agricultural productivity and food security. American foulbrood (AFB) is a highly contagious and destructive bacterial honeybee brood disease caused by Paenibacillus larvae that affects beekeeping worldwide. However, only a minority of bacteria associated with honeybees are harmful. Honeybee-specific Lactic Acid Bacteria (hbs-LAB), a defined group of beneficial bacteria inhabiting the honey crop, have strong antimicrobial properties important for honey production and honeybee health that could be exploited for combating diseases such as AFB. The aim of this thesis was to investigate the effect of hbs-LAB on P. larvae and AFB, both in culture, in individual larval bioassays, and at colony level. First we showed that the laboratory cultivation of the 13 distinct hbs-LAB was significantly improved by the addition of L-cysteine and fructose to the medium and optimized a culture-independent molecular technique for the detection and identification of the individual hbs-LAB species. Secondly the effect of the cell free supernatant, the secretome, from a culture mix of the 13 hbs-LAB species was investigated on P. larvae growth and associated larval mortality. The results showed that this secretome strongly inhibited the multiplication of P. larvae vegetative cells but that spore germination appeared to be unaffected, and that it decreased the mortality of P. larvae infected larvae. Finally it was shown that oral administration of hbs-LAB supplement to honeybee colonies had no influence on colony-level P. larvae spore levels or colony strength. Furthermore, the results showed that although the antibiotic tylosin decreased AFB symptoms in colonies, it had no effect on P. larvae spore levels. In conclusion, the colony-level results do not contradict the antagonistic effects observed in individual larvae in laboratory studies, but rather suggest that supplementary administration of live bacteria may not be the most effective way to harness such effects in a useful application.
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6.
  • Nilsson, Kerstin (författare)
  • To work or not to work in an extended working life? Factors in working and retirement decisions
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In most of the industrialised world, the proportion of older and retired people in the population is continuously increasing. This will have budgetary implications for maintaining the welfare state, because the active working section of the population must fund the non-active and old population. Aim: The overall aim of this thesis was to obtain knowledge about older workers’ work and life situation in association with their planning and decision to retire from working life. Method: The thesis includes one qualitative and three quantitative studies conducted in Sweden. Result: Self-rated health was found to be a better measure than diagnosed disease of whether older workers believed they could work until 65 years or beyond. Health seems not to be a general impediment to working in old age if older workers are satisfied with their work situation and have enough time and opportunities to recover from fatigue. In one of Sweden’s most hazardous work environments, older workers were not injured significantly more often than younger workers. Good mental and physical work environment, moderate working pace and working time, and the right competence and possibility for skills development were factors determining whether older workers believed they can extend their working life. Attitude to older workers in the organisation, motivation and work satisfaction were factors determining whether older workers want to extend working life. Health, personal economic incentives, family/leisure pursuits and attitude to pension in society affected both whether people believed they can and wanted to extend their working life. In their final retirement decision, older workers considered: i) their possibility to balance and adapt functional ageing and health to a sustainable work situation; ii) their economic situation; iii) possibilities for social inclusion and coherence; and iv) possibilities for meaningful activities. Whether these requirements were best fulfilled in or outside working life determined the decision to continue working or to retire. Conclusion: If it is desirable for society that people will to extend their working life, both the “can work” and the “want to work” factors need to be met. It is important to provide a good fit inside working life. This requires a focus not only on older workers, but also on organisations and managers in order to provide incentives that keep older workers in the work force.
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7.
  • Hosseini Maaf, Bahram (författare)
  • Genetic Characterisation of Human ABO Blood Group Variants with a Focus on Subgroups and Hybrid Alleles
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • ABO is the most important blood group system in transfusion medicine and transplantation immunology. The ABO blood groups differ by the presence or absence of antigens on RBCs and antibodies in plasma. Accurate determination of ABO status is critical. Genomic typing can increase the precision of blood group determination in complicated cases, e.g. when variant expression of A or B antigen is encountered. The overall aim of this study was to compare the molecular diversity of ABO alleles with various phenotypes, and to contribute to our knowledge of the ABO gene and encoded glycosyltransferases. Novel alleles (six Aweak, eleven Bweak, seven O) were identified containing single-point mutations. Structure/function studies explained the weakening of some B subgroup glycosyltransferases. Two new hybrid Ax alleles were characterised. Analysis of introns 2-5 revealed 44 previously unknown, allele-related polymorphisms that proved valuable allelic markers. These findings enabled localisation of cross-over regions in two other new hybrids: 1) an O1v allele fused with an A2 allele, 2) the novel O1bantu-A2 combination that explained the Abantu phenotype. Phylogenetic and population analyses indicated that O1bantu is a unique and distinct evolutionary lineage so far only found among individuals of African descent. Of clinical importance, a new approach to ABO genotyping was developed that identifies all common alleles, most null and weak A/B subgroups as well as hybrid alleles resulting from recombinational crossing-over events. In summary, 30 novel alleles were identified and characterized, representing 30% of all alleles reported since the start of this study in 2001.
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8.
  • Qian, Hong (författare)
  • Regulation of Hematopoietic Stem and Progenitor Cells by Bone Marrow Niche Components
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Throughout the lifespan of an individual, enormous numbers of mature blood cells are generated by hematopoietic stem cells (HSCs) in the bone marrow (BM). The HSC is a cell that can self-renew to maintain the HSC pool and differentiate into all types of mature blood cells. HSCs can also be mobilized out of the BM into blood and can be isolated from different sources including mobilized blood, umbilical cord blood, BM and fetal liver for clinical and experimental purposes. HSCs are widely used as an effective therapy for treatment of hematopoietic and some non-hematopoietic diseases. HSCs reside and develop in the BM in specialized microenvironments, termed niches. However, specific niche components and the molecular mechanisms underlying the regulation of HSC self-renewal, differentiation and migration by the niche remain poorly defined. In the present thesis, we have analysed the interactions of hematopoietic stem and progenitor cells (HSPCs) with niche components and their role in the regulation of HSC migration, self-renewal and differentiation. Specifically, the functional role of integrin receptors in HSPC migration and the role of the blood cell growth factor thrombopoietin (THPO) in HSC maintenance during hematopoietic cell development and after transplantation have been studied. By using both function-blocking antibodies and integrin alpha6 gene-deleted embryos in a mouse transplantation model, we have found that integrin alpha6 receptor, highly expressed on HSPCs, is important for homing of adult HSCs and HPCs to BM in vivo. Furthermore, we have shown that integrin alpha6 receptor is not involved in fetal liver HSC homing and engraftment, whereas it plays a role in fetal liver HPC homing. Importantly, alpha4 was found to be essential for both adult BM and fetal liver HSC and HPC homing. By using functional assays and phenotypic HSC analysis of Thpo-/- mice, we demonstrated that THPO is critically involved in postnatal and post-transplantation HSC maintenance. The distinct role of THPO in postnatal HSC maintenance was accompanied by accelerated HSC cell cycle kinetics in Thpo-/- mice and reduced expression of cyclin-dependent kinases p57Kip2 and p19INK4D. Taken together, we have for the first time provided the evidence that integrin alpha6 functions as a homing receptor for BM HSPCs and fetal liver HPCs, and that THPO regulates the maintenance of postnatal quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion. Notably, our studies on functions of integrin alpha6 and THPO in HSCs emphasize ontogeny related differences in HSC regulation.
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9.
  • Borg, Christel (författare)
  • LIVSTILLFREDSSTÄLLELSE HOS ÄLDRE, SÄRSKILT MED NEDSATT FUNKTIONSFÖRMÅGA SAMT INFORMELLA VÅRDARE I relation till hälsa, självkänsla, sociala och ekonomiska resurser i ett svenskt och europeiskt perspektiv
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • I relation till hälsa, självkänsla, sociala och ekonomiska resurser i ett svenskt och europeiskt perspektiv. Knowledge of factors contributing to life satisfaction among older people is needed, both in the context of those with reduced self-care capacity and among healthy older people and those providing help to others. Such knowledge may be helpful in developing primary and secondary interventions. The overall aim of this thesis was to investigate life satisfaction and its relation to factors such as physical and mental health and social and financial resources among people (60?89 years old) with and without reduced self-care capacity in six European countries, and among informal caregivers (50?89 years old) in Sweden. The aim was further to investigate the extent, need and type of support provided or desired among informal caregivers. This is part of the cross-national European Study of Adults? Wellbeing (ESAW) including six European countries N=12 478 (the Netherlands, Luxemburg, Italy, Austria, UK and Sweden). The Older Americans? Resources Schedule (OARS), Life Satisfaction Index Z (LSIZ) and Rosenberg self-esteem scale were used. Study I comprised 522 people (65?89 years old) with reduced self-care capacity, study II comprised 151 informal caregivers with a high caregiving extent, 392 with a low caregiving extent and 1258 non-caregivers from the Swedish sample. In study III 2195 people with reduced self-care countries. The data were analysed by descriptive and inferential statistics using non-parametric statistics, logistic and linear regression. Low life satisfaction (LSIZ) was related to higher age, being a woman, high degree of reduced self-care capacity, living in special accommodations, feeling lonely and poor financial resources. Feeling lonely, reduced self-care capacity, feeling worried, poor health and poor financial resources in relation to needs predicted low life satisfaction (Paper I). Frequent caregivers with a high extent of caregiving had lower LSIZ than those with less frequent caregiving and noncaregivers, while no differences were found between less frequent caregivers and non-care caregivers in LSIZ. Lower LSIZ was associated with not being employed, low social resources, not refreshed after a night's sleep, poor health, and frequent caregiving (Paper II). In paper III it was found that there were differences as well as similarities in factors predicting LSIZ in that self-esteem and overall health were important in all countries among older people with reduced self-care capacity and reduced self care capacity in three of six countries, whilst in paper IV four factors were found to be common in all ESAW countries. The factors were social resources, financial resources, feeling greatly hindered by health problems and low self-esteem. Factors of importance for life satisfaction thus seem to differ depending on the personal situation and social and political system. These differences should be taken into account when outlining and providing preventive, rehabilitative and support for these groups.
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10.
  • Buza-Vidas, Natalija (författare)
  • Cytokine Regulation of Hematopoietic Stem Cells and Lymphopoiesis
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Large numbers of blood cells need to be continuously replaced in order to sustain the crucial functions of the immune system, oxygen transport and blood clotting. The large diversity of cell types required to maintain the integrity of the blood system are all produced from blood forming or hematopoietic stem cells (HSCs). HSCs have the unique property of self renewal, ensuring life-long replenishment of all the blood cell types. Hematopoietic growth factors, so called cytokines, have previously been demonstrated to be important for the survival and proliferation of committed progenitor cells and development of different blood cell lineages. However, their potential role in regulating HSCs remains to a large degree unresolved. Herein, we provide data that establish the adaptor protein LNK as an important negative regulator of postnatal HSC expansion, acting as an inhibitor of the cytokine Thrombopoietin, known to be important for HSC maintenance and/or expansion. Furthermore, whereas previous studies demonstrated that another cytokine, fms-like tyrosine kinase receptor 3 (FLT3) ligand (FL), is an important regulator of B cell progenitors but has a redundant role in steady state maintenance of mature B cells, we here demonstrate that FL plays a crucial role in the regeneration of not only B cell progenitors but also mature B cells after bone marrow (BM) transplantation and chemotherapy. In addition, through studies of FL-deficient mice we show that FL plays an important role in maintaining conventional B cells with age, but is redundant in maintaining a normal compartment of fetally/postnatally derived B1 and marginal zone B cells. It has been disputed whether FL also is important in HSC regulation. Our present findings establish that FL is not important for regulating HSC maintenance or expansion neither during fetal development or in adult steady state hematopoiesis, nor following BM transplantation or chemotherapy-induced BM ablation. Finally, through identification of a multipotent progenitor in adult BM, with sustained granulocyte-monocyte and lymphocyte potential, but little or no megakaryocyte and erythroid potential, we provide evidence for a strict separation of myelopoiesis and lymphopoiesis, not being the first lineage commitment step of HSCs.
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