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SAMMANFATTNING Crohns sjukdom/CD och ulcerös kolit/UC är de två mest kända sjukdomarna som lyder under samlingsnamnet inflammatoriska tarmsjukdomar/IBD. Sjukdomarna karaktäriseras av kroniska diarréer där blodiga diarréer är ett kardinal symtom vid UC. Uppkomstmekanismen för IBD är okänd men immunologiska processer spelar en betydande roll för patogenesen av sjukdomarna. Sjukdomarna kan uppstå på grund av en obalans mellan pro-inflammatoriska och anti-inflammatoriska cytokiner. Dessutom förekommer autoimmun reaktivitet riktade mot olika antigen t.ex. neutrofiler. Syftet med detta projekt var att sätta upp en metod för ELISA-analys av serumprover, för att kunna analysera om patienter med CD eller UC har ökade halter av neutraliserande antikroppar mot tumörnekrotisk faktor/TNFα i serum jämfört med friska kontroller. I studien analyserades 60 patientprover; 30 från patienter med CD, 30 från patienter med UC, för ökade halter av anti-TNFα antikroppar i serum jämfört med friska blodgivare med ELISA-teknik. De erhållna resultaten visade att det fanns ökad antikroppsreaktivitet mot TNFα framförallt hos UC patienter men även till viss del hos CD patienter. Vi kunde dock inte neutralisera dessa antikroppar med löslig rTNF. Med detta provmaterial kan man konstatera att ELISA-metoden har fungerat bra och det var också syftet med projektet. Man kan även konstatera att det är viktigt att säkerställa att det man mäter är specifikt för det man söker.       Nyckelord: IBD, CD, UC, TNFα, ELISA, autoantikroppar.

In this thesis focus has been to increase the knowledge and understanding of some of the mechanisms responsible for drug resistance in acute myeloid leukemia, as well as identify possibilities to predict drug resistance at diagnosis. We have studied the intracellular behavior of cytostatic drugs and their main metabolites (paper I) and the cellular response to cytostatic drugs (paper III). A new flow cytometry in vitro chemosensitivity assay was developed, to enable identification of viable myeloid cells and determination of drug sensitivity (paper II). Finally, possible new markers involved in drug resistance were investigated (paper IV). In conclusion we found that idarubicin and daunorubicin are equally toxic at the same intracellular concentrations. The contribution of the main metabolites to the cytotoxic effects of idarubicin and daunorubicin, in both drug sensitive and drug resistant human myeloid leukemia cells, is low. It is most likely the pharmacokinetic properties of idarubicin and daunorubicin that confer their main cytotoxic effect. With the new flow cytometry chemosensitivity assay we selectively identified viable CD13/CD33 expressing myeloid cells and found that the cytotoxicity results correlated to clinical parameters, such as secondary AML and resistant disease. Short-term exposure of leukemia cell lines with different levels of drug resistance to ara-C revealed that Pgp mRNA and protein ex-pression levels, as well as GSTπ mRNA levels, were rapidly up-regulated. Clinically, this up-regulation may be of importance for the sequential scheduling of daunorubicin and ara-C during the induction treatment of AML. CRIM1 has never been studied in the context of drug resistance before. We show for the first time that baseline expression of CRIM1 mRNA is much higher in drug resistant leukemia cells compared to drug sensitive cells. We also found a co-variance between CRIM1 and Pgp mRNA expression levels in leukemia cell lines with different levels of drug resistance, suggesting that CRIM1 may be useful as a marker of drug resistance.

Eating disorders and binge eating has repeatedly been shown to be common in surgical and behavioural weight loss treatments. Due to methodological variations and shortcomings in previous research, there is insufficient information about how eating disorders and binge eating are associated with outcome in weight loss treatments. There is therefore no consensus on how eating pathology should be adressed in weight loss treatments, which has led to large differences in the clinical practice. The main aim of this thesis was to address the issues of eating disorders and binge eating in weight loss treatments, and to investigate how binge eating is associated with long-term treatment outcome.