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In the present thesis molecular genetic methods were used to address different biological and clinical aspects of Philadelphia (Ph) chromosome-positive leukemias and the BCR and ABL genes. In the first study, children with Ph-positive chronic myeloid leukemia (CML) were found to have essentially the same breakpoint locations in BCR as adults, a pattern which differs from the one seen in Ph-positiv
Popular Abstract in Swedish Pyrimidiner är DNA-byggstenar som är essentiella för cellens överlevnad och delning. I mänskliga celler finns pyrimidiner att tillgå antingen genom återupptag eller genom biosyntes (nysyntes). Biosyntesen av pyrimidiner sker i flera steg och i ett av dem spelar enzymet Dihydroorotat dehydrogenas (DHODH) en avgörande roll genom att katalysera en oxidationsreaktion. När cIn the first part of the PhD work, small chemical entities (fragments) found to inhibit human dihydroorotate dehydrogenase (DHODH), were chemically optimized. As part of an ample program at Active Biotech to find new drugs against autoimmune diseases, expanded fragments were repeatedly designed, synthesized and evaluated in a human DHODH assay. Potent inhibitors were identified within three classe
Popular Abstract in Swedish Atmosfäriskt nedfall är den största källan till miljögiftet PCB i sötvatten. I flertalet vattendrag, exempelvis Emån, fungererar också sediment som en källa. Ett pappersbruk i anslutning till Emån hade använt returpapper som innehöll PCB som råvara. PCB följde med utsläppen till ån och lagrades in i sedimenten. Miljögiftet läckte sedan ut långsamt till vattnet. Största Atmospheric deposition is one source of persistent pollutants such as polychlorinated biphenyls (PCB) in aquatic environments. Other point sources can also contribute to the PCB loadings in the water. In the Emån River, in southeast Sweden, contaminated sediment was a source of PCB, the largest deposits of it being found in a small lake connected with the river, Lake Järnsjön, the sediment of it c
Popular Abstract in Swedish Vi har studerat hur man kan använda immunsystemet för att behandla råttor med hjärntumör (maligna gliom). Eftersom råttor väldigt sällan utvecklar hjärntumörer, så måste vi injicera tumörceller i hjärnan själva. Om djuren inte får någon behandling dör de vanligen inom ca. 24 dagar. Får de däremot en injektion i buken eller under huden på benet med genmanipulerade tumörcMalignant glioma is, with rare exceptions in younger adults, an uncurable brain tumor, as very few survive more than 1-2 years after diagnosis. Despite advances in recent years, current treatments such as surgery, radiotherapy and chemotherapy only prolongs the life of the patients. Because of the poor prognosis, several additional therapies have been investigated and are under development, such a
Given the increasing interest in the association between exposure to air pollution and adverse health outcomes, the development of models that provide accurate spatio-temporal predictions of air pollution concentrations at small spatial scales is of great importance when assessing potential health effects of air pollution. The methodology presented here has been developed as part of the Multi-Ethn
An initial model in the crystallographic structure determination process, usually contains many errors. To produce an accurate model, one must carry out several cycles of crystallographic refinement. Because of the limited resolution typically obtained for biomolecules, the experimental data are usually supplemented by some sort of chemical information, typically in the form of a molecular-mechani
Popular Abstract in Swedish POPULÄRVETENSKAPLIG SAMMANFATTNING PÅ SVENSKA I blodet finns en mängd olika celltyper som alla har sin specifika funktion. De röda blodkropparna (erytrocyterna), transporterar livsnödvändigt syre till kroppens alla vävnader. De vita blodkropparna (leukocyterna), vilka inkluderar lymfocyter, monocyter och granulocyter, deltar i kroppens immunförsvar och skyddar kroppen Hematopoiesis is a highly complex process by which a range of specialized blood cells are generated from a small pool of multipotent stem cells in the bone marrow. The survival, proliferation, and differentiation of hematopoietic stem cells are tightly regulated by both soluble and membrane-bound cytokines produced within the bone marrow microenvironment. Kit Ligand (KL) and Flt3 Ligand (FL) are t
Popular Abstract in Swedish Förmågan att ha tillgång till energi oberoende av ett varierande födointag är livsavgörande. Kroppen har därför på ett högst effektivt sätt löst detta genom att lagra energi i form av fett i fettceller, vilka finns i fettväven. Dessa fettdepåer, vilka utgörs av triglycerider (en triglycerid består av ett glycerol med tre påkopplade fettsyror), byggs upp då födointaget äTriglycerides in the adipocyte are hydrolysed by means of three consecutive reactions through the combined action of two lipases: hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL). HSL catalyses the first and rate-limiting step, i.e. the hydrolysis of triglycerides to diglycerides, and the subsequent hydrolysis of diglycerides and monoglycerides. However, MGL is needed to assure comple
Popular Abstract in Swedish Utveckling av blodbildande celler sker i benmärgens mikromiljö, som består av cytokiner och tillväxtfaktorer, stromaceller samt extracellulära matrixmolekyler. Extracellulära matrixproteiner och stromaceller i benmärgen utgör en strukturell miljö för hematopoietiska celler, men adhesiva cell-cell och cell-matrix interaktioner påverkar också direkt hematopoietiska cellerDevelopment of hematopoietic cells in bone marrow takes place in association with the hematopoietic microenvironment. Extracellular matrix (ECM) molecules and stromal cells in bone marrow provide a structural environment for hematopoietic cells, but they also directly influence proliferation, differentiation and migration of cells by signal transduction mediated by ligand binding to cell surface a
The subject of this thesis is the clinical use of the oesophageal electrode in electrocardiology. The three areas covered are oesophageal electro- cardiography, the biophysics of transoesophageal atrial stimulation (TAS) and the clinical utility of TAS. The literature is reviewed with respect to these areas. TAS was performed in 64 patients with documented supraventricular tachycardia (SVT) or a
Popular Abstract in Swedish FN:s barnkonvention formulerar barns och ungas behov i termer av mänskliga rättigheter. Sverige ratificerade konventionen efter ett beslut i riksdagen den 21 juni 1990, utan att reservera sig på någon punkt. Konventionens budskap kan sammanfattas i tre ord: Barn skall respekteras. Vuxna skall se barnet, sträva efter att förstå det och vidta åtgärder som bedöms vara tillThe main purpose was to investigate children's participation in the decision-making processes in health care. Twenty-four children (0-18 år)admitted to hospital, their parents, and the staff present were observed during totally 135 hours in order to (i) identify the children's needs, (ii) their participation in the decision-making processes, and (iii) their parents' participation. Twenty-six child
Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure disorder in which pure red blood cell aplasia is associated with physical malformations and a predisposition to cancer. Twentyfive percent of patients with DBA have mutations in a gene encoding ribosomal protein S19 (RPS19). Our previous proof-of-concept studies demonstrated that DBA phenotype could be successfully treated using len
UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo a
Understanding atmospheric response to radiative forcing, including the intensity and distribution of wind patterns is critical as this might have important implications in the coming decades. Long-term episodes of reduced solar activity (i.e. Grand Solar Minima, GSM) have triggered rapid climate change in the past, recorded in proxy-based records, including varved sediments from Meerfelder Maar, G
Land biosphere processes are of central importance to the climate system. Specifically, ecosystems interact with the atmosphere through a variety of feedback loops that modulate energy, water, and CO2 fluxes between the land surface and the atmosphere across a wide range of temporal and spatial scales. Human land use and land cover modification add a further level of complexity to land-atmosphere
Social media facilitates the sharing of ideas, thoughts and information about older people and later life through online networks and communities in contemporary society. Social media content about older people has become important for understanding media representations of older people, but it has not been sufficiently studied. Recent studies suggest that older people are predominantly represente
Soil microorganisms regulate the decomposition of organic matter. However, microbial activities can also be rate-limited by the resource in lowest supply. Arctic ecosystems are being exposed to pronounced climate warming, with arctic greening, treeline advance and shrubification resulting in increased plant-derived carbon (C) inputs to soils, and faster rates of decomposition releasing mineral nut
