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Chen, Yu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 75-78). / Abstracts in English and Chinese. / Isolation and Identification of Differentially Expressed Protein in Serum of Patients with Sleep Disorders --- p.I / Abstract --- p.IV / 論文摘要 --- p.VII / Acknowledgements --- p.IX / Table of Contents --- p.X / List of Figures --- p.XII / List of Tables --- p.XII / List of Abbreviations --- p.XIII / Chapter Chapter 1: --- Introduction --- p.2 / Chapter 1.1 --- Definition of narcolepsy --- p.2 / Chapter 1.2 --- Symptoms of narcolepsy --- p.2 / Chapter 1.2.1 --- Excessive Daytime Sleepiness (EDS) --- p.2 / Chapter 1.2.2 --- Cataplexy --- p.2 / Chapter 1.2.3 --- Associated features --- p.3 / Chapter 1.3 --- Prevalence of narcolepsy --- p.4 / Chapter 1.4 --- Pathophysiology and molecular genetics of narcolepsy --- p.7 / Chapter 1.4.1 --- Pathophysiology of narcolepsy --- p.7 / Chapter 1.4.2 --- Molecular genetics research --- p.8 / Chapter 1.5 --- Diagnostic criteria for narcolepsy --- p.12 / Chapter 1.6 --- Treatment of narcolepsy --- p.16 / Chapter 1.7 --- The Burden of narcolepsy --- p.18 / Chapter 1.8 --- Human blood serum/plasma --- p.19 / Chapter 1.9 --- Cerebrospinal fluid (CSF) --- p.23 / Chapter 1.10 --- Aims of study --- p.26 / Chapter Chapter 2: --- Materials and Methods --- p.28 / Chapter 2.1 --- Participants and measurements --- p.28 / Chapter 2.1.1 --- Participants --- p.28 / Chapter 2.1.2 --- Diagnosis measurements --- p.28 / Chapter 2.2 --- "Serum extraction, albumin and IgG depletion" --- p.30 / Chapter 2.2.1 --- Albumin and IgG Depletion Kit --- p.30 / Chapter 2.2.2 --- Chemicals and reagents --- p.30 / Chapter 2.2.3 --- Preparation of solutions --- p.30 / Chapter 2.2.4 --- Procedure --- p.30 / Chapter 2.3 --- Reversed Phase High Performance Liquid Chromatography (RP-HPLC) --- p.32 / Chapter 2.3.1 --- RP-HPLC method --- p.32 / Chapter 2.3.2 --- Chemicals and reagents --- p.33 / Chapter 2.3.3 --- Preparation of mobile phases --- p.33 / Chapter 2.3.4 --- Procedure --- p.33 / Chapter 2.4 --- MALDI-TOF/TOF Mass Spectrometry --- p.35 / Chapter 2.4.1 --- Chemicals and reagents --- p.35 / Chapter 2.4.2 --- Preparation of solutions --- p.35 / Chapter 2.4.3 --- Procedure --- p.35 / Chapter 2.5 --- SDS-PAGE and double staining --- p.37 / Chapter 2.5.1 --- Chemicals and reagents --- p.37 / Chapter 2.5.2 --- Preparation of solutions --- p.37 / Chapter 2.5.3 --- Procedure --- p.39 / Chapter 2.6 --- N-terminal amino acid analysis --- p.42 / Chapter 2.6.1 --- Procedure --- p.42 / Chapter 2.6.2 --- Sequence analysis --- p.42 / Chapter 2.7 --- CSF analysis --- p.43 / Chapter Chapter 3: --- Results --- p.45 / Chapter 3.1 --- Albumin and IgG depletion of human serum samples --- p.45 / Chapter 3.2 --- Peak identification --- p.47 / Chapter 3.2.1 --- Peak identification on HPLC profiles --- p.47 / Chapter 3.2.2 --- Statistical results --- p.51 / Chapter 3.2.3 --- Family cases analysis --- p.54 / Chapter 3.3 --- MALDI-TOF/TOF Mass Spectrometry --- p.56 / Chapter 3.4 --- SDS-PAGE and double staining --- p.58 / Chapter 3.5 --- Protein sequence analysis --- p.60 / Chapter 3.6 --- Cerebrospinal fluid (CSF) analysis --- p.62 / Chapter Chapter 4: --- Discussion --- p.65 / Chapter 4.1 --- RP-HPLC methods --- p.65 / Chapter 4.2 --- The detected peptide fragment and Hlark --- p.66 / Chapter 4.2.1 --- "Human Lark protein (Hlark, hlark)" --- p.66 / Chapter 4.2.2 --- Circadian clocks --- p.67 / Chapter 4.2.3 --- "Hlark, circadian rhythm and narcolepsy" --- p.71 / Chapter 4.3 --- Familial and genetic analysis --- p.72 / Chapter 4.4 --- Clinical implications --- p.73 / Chapter 4.5 --- Conclusion --- p.74 / References --- p.75

Call number: LD2668 .T4 1961 C44

Histidine-rich glycoprotein (HRG) is a plasma protein that regulates key cardiovascular processes such as coagulation, angiogenesis and immune response. The protein consists of six distinct functional domains: two N-terminal domains (N1 and N2), two proline-rich regions (PRR1 and PRR2), a central histidine-rich region (HRR) and a C-terminal domain. The HRR binds Zn²⁺, which alters the affinity of HRG towards various ligands including the anticoagulant, heparin. A key aim of this study was to structurally characterise HRG. The 1.93 Å crystal structure of the HRG N2 domain presented here represents the first crystallographic snapshot of the molecule. The N2 domain is cystatin-like and N-glycosylated at Asn184. An S-glutathionyl adduct was observed at Cys185, providing in vivo evidence that release of an anti-angiogenic HRR/PRR fragment is controlled in part by a redox mechanism, representing a novel further role for GSH in regulation of angiogenesis. Since Zn²⁺ regulates some of the functions of HRG, the dynamics of Zn²⁺ in plasma were investigated using a combination of ITC, ELISA and thrombin assay systems. Zn²⁺ is normally associated with albumin in circulation, but its ability to bind Zn²⁺ is allosterically inhibited upon fatty acids binding to albumin. Elevated plasma fatty acid levels are associated with some disease states. It is proposed that this may alter the proportion of Zn²⁺ bound to HRG, which could in turn activate thrombin to promote coagulation. These studies provide evidence to suggest that Zn²⁺-dependent activation of HRG (following fatty acid binding to albumin) may play a role in the development of haemostatic complications in susceptible individuals. Finally, the Zn²⁺ binding ability of albumin was probed in order to locate unidentified sites using recombinant albumin mutants. H9A, H67A, E252A, D256A and H288A mutants all exhibited diminished Zn²⁺ binding ability, indicating that these residues are involved directly or indirectly in Zn²⁺ binding.

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 42-44). Also available on the World Wide Web.

Thesis (M.S.)--Rutgers University, 2009. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 89-94).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Hawaii at Manoa, 2004. / Includes bibliographical references (leaves 137-145). / Also available by subscription via World Wide Web / xiv, 145 leaves, bound ill. (some col.) 29 cm