Lai Ching Ha. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 225-243). / Title --- p.1 / Abstract --- p.2 / Acknowledgments --- p.4 / Contents --- p.5 / Abbreviations --- p.10 / List of Figures --- p.12 / List of Tables --- p.15 / Chapter Chapter 1 --- Review on Inherited Metabolic Diseases --- p.18 / Chapter 1.1 --- Development of the concept of inherited metabolic diseases (IMD) --- p.18 / Chapter 1.2 --- Frequency of inherited metabolic diseases --- p.20 / Chapter 1.3 --- Molecular basis of mutations in inherited metabolic diseases --- p.22 / Chapter 1.3.1 --- Point mutations --- p.22 / Chapter 1.3.2 --- Small deletions and insertions --- p.25 / Chapter 1.3.3 --- large deletions or duplications --- p.26 / Chapter 1.4 --- Pathological consequences of protein defect resultingin IMD --- p.27 / Chapter 1.4.1 --- End product --- p.28 / Chapter 1.4.2 --- Precursor accumulation --- p.28 / Chapter 1.4.3 --- Unusual metabolites --- p.29 / Chapter 1.5 --- Heterogeneity of inherited metabolic diseases --- p.29 / Chapter 1.5.1 --- Genetic heterogeneity --- p.29 / Chapter 1.5.2 --- Variations of expression in different cells --- p.31 / Chapter 1.6 --- Diagnosis of inherited metabolic diseases --- p.32 / Chapter 1.6.1. --- Biochemical investigations --- p.32 / Chapter 1.6.2 --- Identification of accumulated or missing metabolites --- p.33 / Chapter 1.6.3 --- Direct analysis of enzymes and proteins --- p.34 / Chapter 1.6.4 --- Molecular investigations --- p.34 / Chapter 1.7 --- Treatment of inherited metabolic diseases --- p.40 / Chapter 1.7.1 --- Treatment at the clinical phenotype level --- p.41 / Chapter 1.7.2 --- Treatment at the metabolite level --- p.41 / Chapter 1.7.3 --- Treatment at the dysfunctional protein level --- p.43 / Chapter 1.7.4 --- Transplantation --- p.44 / Chapter 1.7.5 --- Gene therapy --- p.45 / Chapter 1.8 --- Inherited metabolic diseases in Hong Kong --- p.47 / Chapter 1.9 --- General Aim --- p.48 / Chapter Chapter 2 --- Study of Inherited Metabolic Diseases in Mentally Retarded Patients --- p.49 / Chapter 2.1 --- Introduction --- p.49 / Chapter 2.2 --- Aim --- p.52 / Chapter 2.3 --- Materials --- p.53 / Chapter 2.3.1 --- Standards --- p.53 / Chapter 2.3.2 --- Chemical reagents --- p.53 / Chapter 2.3.3 --- Derivatization reagents --- p.54 / Chapter 2.3.4 --- Major equipment --- p.54 / Chapter 2.4 --- Clinical materials --- p.56 / Chapter 2.4.1 --- Subjects --- p.55 / Chapter 2.4.2 --- Blood and urine samples --- p.56 / Chapter 2.5 --- Methods --- p.57 / Chapter 2.5.1 --- General biochemistry tests --- p.57 / Chapter 2.5.2 --- Metabolic screening tests --- p.57 / Chapter 2.5.3 --- Two-dimensional thin layer chromatography --- p.53 / Chapter 2.5.4 --- Identification of urinary organic acids by gas chromatography mass spectroscopy --- p.59 / Chapter 2.5.5 --- Amino acid analysis by high performance liquid chromatography --- p.66 / Chapter 2.6 --- Results --- p.71 / Chapter (A) --- Methodological Aspects / Chapter 2.6.1 --- Identification of urinary organic acids by gas chromatography-mass spectroscopy (GC-MS) --- p.71 / Chapter 2.6.2 --- Amino acid analysis by high performance liquid chromatography (HPLC) --- p.86 / Chapter (B) --- Patient Investigations / Chapter 2.6.3 --- General biochemistry tests --- p.107 / Chapter 2.6.4 --- Serum amino acid profiles --- p.113 / Chapter 2.6.5 --- Urinary organic acid analysis --- p.115 / Chapter 2.6.6 --- Case reports --- p.119 / Chapter 2.7 --- Discussion --- p.123 / Chapter 2.7.1 --- Identification of urinary organic acids by gas chromatography-mass spectroscopy (GC-MS) --- p.123 / Chapter 2.7.2. --- Amino acid analysis by high performance liquid chromatography (HPLC) --- p.130 / Chapter 2.7.3 --- Identification of inherited metabolic diseases (IMD)in an institutionalized mentally retarded patients --- p.136 / Chapter Chapter 3 --- Molecular Investigation of Maple Syrup Urine Disease --- p.140 / Chapter 3.1 --- Introduction --- p.140 / Chapter 3.1.1 --- Branched chain amino acids (BCAA) --- p.140 / Chapter 3.1.2 --- Metabolism of branched chain amino acids --- p.142 / Chapter 3.1.3 --- Maple syrup urine disease (MSUD) --- p.144 / Chapter 3.1.4 --- Classification of maple syrup urine disease --- p.146 / Chapter 3.1.5 --- Screening and diagnosis of maple syrup urine disease --- p.148 / Chapter 3.1.6 --- Treatment of maple syrup urine disease --- p.150 / Chapter 3.1.7. --- Branched chain a-ketoacid dehydrogenase complex (BCKDH) --- p.151 / Chapter 3.1.8 --- "Gene features of human E1α,E1β and E2 subunitsin branched chain α-ketoacid dehydrogenase complex" --- p.153 / Chapter 3.1.9 --- Molecular defects of the BCKDH gene complex --- p.156 / Chapter 3.1.10 --- MSUD in Hong Kong --- p.161 / Chapter 3.2 --- Aim --- p.163 / Chapter 3.3 --- Materials --- p.164 / Chapter 3.3.1 --- Source of skin fibroblasts --- p.164 / Chapter 3.3.2 --- Enzymes --- p.164 / Chapter 3.3.3 --- DNA markers --- p.164 / Chapter 3.3.4 --- Reagent Kits --- p.165 / Chapter 3.3.5 --- Primers --- p.165 / Chapter 3.3.6 --- Chemical reagents --- p.165 / Chapter 3.3.7 --- Nitrocellulose membrane --- p.166 / Chapter 3.3.8 --- Antiserum for Western blotting --- p.166 / Chapter 3.3.9 --- Radioisotopes --- p.166 / Chapter 3.4 --- Methods --- p.168 / Chapter 3.4.1 --- Preparation of buffers and solutions --- p.168 / Chapter 3.4.2 --- Agarose gel electrophoresis --- p.170 / Chapter 3.4.3 --- Preparation of native polyacrylamide gel --- p.171 / Chapter 3.4.4 --- Preparation of sodium dodecyl sulfate (SDS) polyacrylamide gel --- p.172 / Chapter 3.4.5 --- Preparation of denaturing polyacrylamide gel --- p.173 / Chapter 3.4.6 --- Branched chain α-ketoacid dehydrogenase complex enzyme assay --- p.173 / Chapter 3.4.7. --- Identification of the affected subunits in BCKDH complex of MSUD patient and her family members --- p.176 / Chapter 3.4.8 --- Screening of mutation in the BCKDH subunits by RT-PCR-SSCP --- p.178 / Chapter 3.4.9 --- Mutation analysis of whole cDNA fragments of Elα， Elβ and E2 subunits by ds DNA cycle sequencing --- p.184 / Chapter 3.5 --- Results --- p.188 / Chapter 3.5.1 --- Branched chain α-ketoacid dehydrogenase complex enzyme assay --- p.188 / Chapter 3.5.2 --- Identification of the affected subunits in BCKDH complex ofMSUD patient and her family members --- p.188 / Chapter 3.5.3 --- Screening of mutation in the BCKDH subunits by RT-PCR-SSCP --- p.192 / Chapter 3.5.4 --- "Mutation analysis of whole cDNA fragments of Ela, Elβ and E2 subunits by ds DNA cycle sequencing" --- p.204 / Chapter 3.6 --- Discussion --- p.210 / Chapter 3.6.1 --- BCKDH activity in the MSUD patient and her family members --- p.210 / Chapter 3.6.2 --- Investigation of the mutation sites --- p.212 / General Conclusion --- p.222 / Appendix --- p.224 / References --- p.225
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_318341 |
| Date | January 1995 |
| Contributors | Lai, Ching Ha., Chinese University of Hong Kong Graduate School. Division of Pathological Sciences. |
| Publisher | Chinese University of Hong Kong |
| Source Sets | The Chinese University of Hong Kong |
| Language | English |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, 243 leaves : ill. (some mounted) ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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