Although early studies on HCR provided valuable information for its characterization, the functions of HCR remain unclear. / In addition, we also isolated HCR partners in keratinocyte using a yeast two-hybrid screening. Two novel HCR partners, keratin 17 and nm23-H2, were identified. Since the expression of keratin 17 in epidermis has been recognized as a hallmark of psoriatic plaques, our findings support HCR as a candidate gene for psoriasis susceptibility. We speculate that nm23-H2 is involved in endocytosis together with HCR because nm23 also participated in endocytotic pathways. / In this study, we attempted to relate the function of HCR gene to its role in the pathogenesis of psoriasis. We first examined the subcellular localization of HCR. From a series of co-localization experiments, we eventually localized HCR in early endosomes because almost completely overlapped with active Rab4 which regulates vesicle traffic from early endosomes to perinuclear recycling endosomes and to the plasma membrane indicating that HCR may regulate sorting of internalized cargo from early endosomes to the recycling endosomes or back to the cytoplasm. / Psoriasis is a common chronic skin disorder affecting approximately 1-2% of the Caucasian population. A genetic basis for psoriasis susceptibility has been determined, however, the genetic influence of psoriasis is complex. Several genetic linkage studies have been identified. PSORS1 at 6p21.3 which has been narrowed down to a few hundred kilobase intervals around the HLA-C is the most consistently observed susceptibility locus for psoriasis in both linkage analyses and genome wide scans. HCR is a candidate gene lying within the HLA region which was previously named PG8 for 'putative gene 8' and is now more commonly called HCR for 'alpha-helix coiled-coil rod homolog'. The HCR gene is highly polymorphic. SNP association analysis showed that one SNP haplotype, named HCR*WWCC (corresponding to SNPs at nucleotides 307, 325, 1723, 2327, and involving amino acids 103, 109, 575 and 776, respectively), was associated with psoriasis. Early studies showed that the protein was confined to basal keratinocytes in healthy and non-lesional skin, whereas, it was expressed above the tips of basal and suprabasal dermal papillae in psoriatic lesional skin. / Li, Chunman. / "November 2005." / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0810. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 137-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "December 2000." Typescript. Vita. Includes bibliographical references (leaves 177-206). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 237-245).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 89-105).

Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are the most prevalent pathogens to induce mastitis. The pathogenesis of infections induced by E. coli is sophisticatedly modulated by lipopolysaccharide (LPS), LPS binding protein, membrane CD14 (mCD14), and soluble CD14 (sCD14). In the first study, administration of recombinant bovine sCD14 (rbosCDl4) significantly reduced the fatality of LPS challenged mice and the severity of mouse mastitis in terms of clinical signs, bacterial load, and TNF-alpha production. Before investigating the potential of this strategy in dairy cows, endogenous sCD14 in milk was characterized. Based on the data of 396 quarters, the milk concentration of sCD14 was 6.67 +/- 0.44 mug/ml. The stages of lactation affected the concentration of sCD14 in milk, which was higher in transitional milk (0--4 days postpartum). Milk sCD14 also increased during an intramammary LPS challenge, which paralleled with SCC increase. The protective effect of sCD14 on bovine E. coli mastitis was then investigated. It was shown that rbosCDl4 sensitized the mammary gland to recruit leukocytes in response to LPS. To prove that the early recruitment of leukocytes plays a role in preventing intramammary E. coli infections, E. coli mastitis was induced in 9 dairy cows with or without 100 mug rbosCD14. Quarters challenged with E. coli plus rbosCD14 had a more rapid recruitment of neutrophils, a faster clearance of bacteria, reduced concentrations of TNF-alpha and IL-8 in milk, and reduced clinical symptoms than quarters injected with saline. / For S. aureus mastitis, a newly designed trivalent whole-cell vaccine being composed of the most dominant serotypes (T5, T8, and T336) was evaluated. The vaccine was immunized with or without either one of the two adjuvants, aluminum hydroxide (ALUM) and Freund's incomplete adjuvant (FICA). The vaccine, with or without the presence of adjuvants, increased antigen-specific IgG1, IgG2, but not IgM, in serum. However, all formulations only had limited effects on lymphocyte subsets, interferon (IFN)-gamma mRNA expression, and neutrophil phagocytosis in comparison with the control. / Taken together, the results indicated that increasing the concentration of sCD14 in milk might be a potential strategy to prevent or reduce severity of E. coli mastitis. On the other hand, both ALUM and FICA did not augment the immune responses when formulated with trivalent vaccine. A more immunostimulatory adjuvant will be required to improve the efficacy of the novel trivalent vaccine against S. aureus mastitis.

Centrosomes are major microtubule organizing centres that set up an internal microtubule (MT) network contributing to cell shape and to the formation of the mitotic spindle during cell division. Rearrangement of this MT array can be dictated by the centrosome and occurs during cell adhesion, polarization and migration. However, little is known about what regulates centrosome assembly and maintenance. beta1-integrins are common cell surface receptors and we show that beta1-integrin signalling is necessary for modulation of centrosome dynamics. In an attempt to identify the downstream components of beta1-integrin signalling involved, we also discovered that the activation of focal adhesion kinase or integrin linked kinase are not required in maintaining centrosome integrity. This would indicate that a non-canonical signalling beta1-integrin pathway might be involved in controlling centrosomal dynamics. This gives us greater insight into the mechanisms that control centrosomal stability and may lead to the better understanding of diseases like cancer and diseases, i.e. lissencephaly, which involve defects in cell polarization and asymmetric cell division, where the centrosome seems to have an important role.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 3 uppsatser.