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Visar resultat 1 - 5 av 23 avhandlingar som matchar ovanstående sökkriterier.

  1. 1. Mutational Analysis and Redesign of Alpha-class Glutathione Transferases for Enhanced Azathioprine Activity

    Författare :Olof Modén; Bengt Mannervik; Mikael Widersten; Kenneth Tew; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; TEKNIK OCH TEKNOLOGIER; ENGINEERING AND TECHNOLOGY; allelic variants; azathioprine; bioactivation; chimeric mutagenesis; directed evolution; DNA shuffling; enzyme engineering; glutathione transferase; GST; lysate screening; molecular docking; multiple alignment; multivariate analysis; polymorphism; principal component analysis; prodrug; prodrug activation; protein engineering; protein redesign; reduced amino acid alphabet; saturation mutagenesis; semi-rational enzyme engineering; site-directed mutagenesis; structure-activity relationship; structure-based redesign; Biokemi; Biochemistry;

    Sammanfattning : Glutathione transferase (GST) A2-2 is the human enzyme most efficient in catalyzing azathioprine activation. Structure-function relationships were sought explaining the higher catalytic efficiency compared to other alpha class GSTs. LÄS MER

  2. 2. Experimental modulation and suppression of anti-allograft immune response

    Författare :Öyvind Östraat; Malmö Institutionen för kliniska vetenskaper; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; linomide; leflunomide; cyclophosphamide; mycophenolate mofetil; azathioprine; thalidomide; cyclosporin A; ciprofloxacin; flow cytometry; production; IL-2; Rat cardiac transplantation; allograft; Immunology; serology; transplantation; Immunologi; serologi;

    Sammanfattning : Abstract The objective of this investigation was to characterise the immunomodulatory or immunosuppressive effects of single drug treatment and the potential synergistic or additive effects of combined treatment with the focus on ciprofloxacin, thalidomide, mycophenolate mofetil, azathioprine, cyclophosphamide or leflunomide added to cyclosporin A (CyA). A rat cardiac transplant model was used to study graft survival and the influence on lymphocytes was evaluated by in vitro tests. LÄS MER

  3. 3. Liquid Chromatography Coupled to Mass Spectrometry : Implementation of Chemometric Optimization and Selected Applications

    Författare :My Moberg; Jonas Bergquist; Karin E. Markides; Dan Bylund; Douglas B. Kell; Uppsala universitet; []
    Nyckelord :Analytical chemistry; liquid chromatography; mass spectrometry; tandem mass spectrometry; electrospray ionization; inductively coupled plasma; chemometrics; optimization; multivariate data analysis; design of experiments; response surface model; siderophore; azathioprine; peptide; Analytisk kemi;

    Sammanfattning : Liquid chromatography (LC) coupled to mass spectrometry (MS) offers highly selective and sensitive analysis of a wide variety of compounds. However, the use of hyphenated experimental set-ups implies that many parameters may have an effect on the studied response. LÄS MER

  4. 4. Directed Evolution of Glutathione Transferases with Altered Substrate Selectivity Profiles : A Laboratory Evolution Study Shedding Light on the Multidimensional Nature of Epistasis

    Författare :Wei Zhang; Bengt Mannervik; Bengt-Harald Jonsson; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; glutathione transferase; azathioprine; directed evolution; semi-rational design; catalytic mechanism; saturation mutagenesis; reduced amino acid alphabets; molecular docking; protein evolution; multivariate data analysis; epistasis; fitness landscape; evolutionary trajectories; Biochemistry; Biokemi; Biokemi; Biochemistry;

    Sammanfattning : Directed evolution is generally regarded as a useful approach in protein engineering. By subjecting members of a mutant library to the power of Darwinian evolution, desired protein properties are obtained. Numerous reports have appeared in the literature showing the success of tailoring proteins for various applications by this method. LÄS MER

  5. 5. Clinical studies of thiopurine metabolism in inflammatory bowel disease

    Författare :Ulf Hindorf; Lund Medicin; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Gastroenterologi; Gastro-enterology; thiopurine methyltransferase; 6-mercaptopurine; azathioprine; Inflammatory bowel disease; thiopurines; adverse events; methylated metabolites; thioguanine nucleotides;

    Sammanfattning : Inflammatory bowel disease (IBD, i.e. primarily Crohn's disease and ulcerative colitis) is characterised by a chronic or relapsing inflammation of the digestive tract. LÄS MER