Optimising care for patients with chronic Hepatitis B and C

This thesis, entitled “Optimising Care for Patients with Chronic Hepatitis B and C” evaluates how the care of patients with viral hepatitis B and C can be optimised. The most important findings include (1) viral HBV biomarkers HBcrAg, HBV RNA, HBsAg, and/or anti-HBc can be used to assess treatment response and the risk of off-treatment ALT flares in chronic hepatitis B patients (CHB) treated with one year of peginterferon-based therapy. Especially, the combination of viral biomarkers yields superior predictive power. (2) Nucleos(t)ide analogues can be ceased in a selected group of CHB patients after long-term viral suppression. A substantial part of the patients achieved HBsAg loss, but patients are also at risk to develop severe hepatic flares. (3) Retrieval of lost to follow-up hepatitis C patients is feasible and can contribute to (micro-) elimination, but is also time-consuming. (4) Adherence to the current clinical guidelines is suboptimal for hepatitis B screening among patients treated with rituximab, as well as the surveillance of viral hepatitis patients in general practice. Adherence to the current clinical guidelines was high among CHB patients treated in a high expect centre, especially when treated by a viral hepatitis specialist. (5) Finally, medical decision-making might be optimised by a guideline add-on, such as the TherapySelector

Differences of size and shape of active and inactive X-chromosome domains in human amniotic fluid cell nuclei

It is a widely held belief that the inactive X-chromosome (Xi) in female cell nuclei is strongly condensed as compared to the largely decondensed active X-chromosome (Xa). We have reconsidered this problem and painted X-chromosome domains in nuclei of subconfluent, female and male human amniotic fluid cell cultures (46, XX and 46, XY) by chromosomal in situ suppression (CISS) hybridization with biotinylated human X-chromosome specific library DNA. FITC-conjugated avidin was used for probe detection and nuclei were counterstained with propidium iodide (PI). The shape of these nuclei resembling flat ellipsoids or elliptical cylinders makes them suitable for both two-dimensional (2D) and three-dimensional (3D) analyses. 2D analyses of Xi- and Xa-domains were performed in 34 female cell nuclei by outlining of the painted domains using a camera lucida. Identification of the sex chromatin body in DAPI-stained nuclei prior to CISS-hybridization was confirmed by its colocalization with one of the two painted X-domains. In 31 of the 34 nuclei the area AXi for the inactive X-domain was smaller than the area AXa for the active domain (mean ratio AXa/AXi = 1.9 ± 0.8 SD, range 1.0-4.3). The signed rank test showed a highly significant (P r(Xi) demonstrating a generally more elongated structure of Xa. For 3D analysis a confocal scanning laser fluorescence microscope (CSLFM) was used. Ten to 20 light optical sections (PI-image, FITC-image) were registered with equal spacings (approx. 0.4 m). A thresholding procedure was applied to determine the PI-labeled nuclear and FITC-labeled X-domain areas in each section. Estimated slice volumes were used to compute total nuclear and X-domain volumes. In a series of 35 female nuclei most domains extended from the top to the bottom nuclear sections. The larger of the two X-chromosome domains comprised (3.7 ± 1.7 S.D.)% of the nuclear volume. A mean ratio of 1.2 ± 0.2 SD (range 1.1-2.3) was found for the volumes of the larger and the smaller X-domains in these female nuclei. In a series of 27 male amniotic fluid cell nuclei the relative X-chromosome domain volume comprised (4.0 ± 2.6 S.D.)%. These findings indicate that differences in the 3D expansion of active and inactive X-chromosome domains are less pronounced than previously thought. A current model suggests that chromosome domains consist of a compact core surrounded by loosely coiled outer chromatin fiber loops. The latter fraction may be considerably larger in Xa- as compared to Xi-domains. We suggest that the interactive outlining procedure used in the 2D analyses included the loosely structured domain periphery more accurately, while the threshold algorithm applied to light optical sections delineated the more compact core of the domains, leading to smaller and more similar volume estimates of Xa and Xi. Present limitations of nuclear and chromosome domain volume measurements using confocal laser scanning microscopy are discussed

Counting problems for number rings

In this thesis we look at three counting problems connected to orders in number fields. First we study the probability that for a random polynomial f in Z[X] the ring Z[X]/f is the maximal order in Q[X]/f. Connected to this is the probability that a random polynomial has a squarefree discriminant. The second counting problem counts the number of subrings within maximal orders. We know that the number of subrings of given index is finite. We determine bounds for the number of suborders in terms of the rank of the maximal order and the index of the suborder. Connected to this is a question from Manjul Bhargava on the number of suborders in quintic rings. The final problem deals with class groups. There are bounds known for the class number of a maximal order, and we use these bounds to bound the class number of general orders.UBL - phd migration 201

Production and characterization of monoclonal antibodies raised against recombinant human granzymes A and B and showing cross reactions with the natural proteins

The human serine proteases granzymes A and B are expressed in cytotoplasmic granules of activated cytotoxic T lymphocytes and natural killer cells. Recombinant granzyme A and granzyme B proteins were produced in bacteria, purified and then used to raise specific mouse monoclonal antibodies. Seven monoclonal antibodies (mAb) were raised against granzyme A, which all recognized the same or overlapping epitopes. They reacted specifically in an immunoblot of interleukin-2 (IL-2) stimulated PBMNC with a disulfide-linked homodimer of 43 kDa consisting of 28 kDa subunits. Seven mAb against granzyme B were obtained, which could be divided into two groups, each recognizing a different epitope. On an immunoblot, all mAb reacted with a monomer of 33 kDa protein. By immunohistochemistry, these mAb could be used to detect granzymes A and B expression in activated CTL and NK cells. The availability of these mAb may facilitate studies on the role of human cytotoxic cells in various immune reactions and may contribute to a better understanding of the role of granzmes A and B in the cytotoxic response in vivo

Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.MTT was supported by Engineering and Physical Sciences Research Council (EPSRC) Impact Acceleration Account (IAA) and Higher Education Innovation Funds (HEIF). MTT and HW was supported by British ConsulateGeneral Chongqing, the Innovation China UK (ICUK) Programme office and QM Innovation Ltd, Queen Mary University of London. HM, HD, XD, ZT, RL, KS, KZ, HC, HX, JW, QG and YZ were supported by the Guizhou Department of Education, Guizhou Science and Technology Department and Guizhou Medical University