The absorption of methionine and methionylglycine (Met-Gly) across sheep (average BW = 38 kg) ruminal and omasal epithelia was studied using parabiotic chambers. Ruminal tissue demonstrated a greater ability to accumulate both substrates. Omasal tissue demonstrated a greater ability to translocate methionine and Met-Gly and a greater total absorption of both. Intact Met-Gly was transferred across both tissues. More was hydrolyzed by omasal epithelia. Within tissues, the total absorption of substrates did not differ. Evidence for carrier-mediated absorption was not observed. The ability to express exogenous mRNA in defolliculated Xenopus laevis oocytes was developed using sucrose gradient size-fractionated poly(A)⁺ RNA (RNA) isolated from the jejunal epithelial tissue of pig (average BW = 33.8 kg). Compared to water-injected oocytes, RNA injected oocytes displayed greater rates of Nat-independent lysine and leucine absorption. RNA-induced uptake of lysine (Kt = 52 uM) and leucine (Kt = 97 uM) was inhibited by 5 mM leucine and lysine, respectively, by .2 mM cysteine, but not by 5 mM glutamate. RNA-induced lysine and leucine absorption also was inhibited when oocytes were injected with RNA plus DNA oligomers that were complementary to the cloned human kidney b⁰‘⁺ transporter. Oocytes were injected with RNA isolated from omasal epithelial tissue of sheep (average BW = 67.5 kg) to identify potential peptide and amino acid transport proteins. Injection of specific RNA fractions induced greater rates of glycylsarcosine (Gly-Sar) uptake, as compared to water injection of oocytes. Media pH of less than 6.5 was required for induced Gly-Sar uptake. Induced Gly-Sar uptake required a pH of less than 6.5, was saturable (Kt = .40 mM), and was inhibited by 5 mM carnosine, Met-Gly, glycylleucine, but not by glycine. The RNA-induced Gly-Sar absorption was completely inhibited when oocytes were co-injected with RNA and DNA oligomers that were complementary to the cloned rabbit H⁺/peptide cotransporter. When oocytes were assayed for their ability to absorb lysine, RNA-induced lysine absorption was determined to be Na⁺-independent and to display b⁰‘⁺-like transport activity. Collectively, these results indicate that sheep omasal epithelia possess the potential to absorb free and peptide-bound amino acids by non-mediated processes and possess mRNA that encode for Ht-dependent dipeptide and b⁰‘⁺ transport protein activity. mRNA that encodes for b⁰‘⁺-like transport activity was identified in the jejunal epithelium of growing pigs. / Ph. D.

Leung Pak Heng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 163-189). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Aim. The human organic cation transporter subtype 2 (OCT2) is highly expressed in the renal tubular epithelium and can play an important role in the renal clearance of many drugs and drug-drug interactions occurring in the kidney. The purposes of this study are: (1) to investigate the genetic polymorphisms of OCT2 in Chinese population; (2) to evaluate the potential genotype-phenotype relationship involving OCT2 polymorphism in human subjects; and (3) to identify the SNPs in proximal promoter/enhancer region and assess their functional significance. / Conclusion. The present study demonstrated the existence of genetic polymorphisms of OCT2 gene in the Chinese population and for the first time showed that a ncSNP 808G>T is associated with a reduced renal transport function and can significantly impact the magnitude of drug interactions. Our study also for the first time found that a promoter polymorphism (-1283 T>C) is associated with an altered promoter activity in vitro, but no such relationship was observed with this SNP in the in vivo metformin study. Thus, it was the ncSNP 808G>T but not the -1283T>C in promoter that was associated with variations in the metformin renal clearance. (Abstract shortened by UMI.) / Method. One hundred and twelve Hong Kong Chinese subjects were recruited and their DNA samples were obtained. / Results. A total of 13 SNPs were identified in the coding and surrounding non-coding regions of OCT2, with minor allele frequencies (MAF) ranged from 4.5% to 24.7%. From these SNP data sets, 28 haplotypes were inferred with 4 being the common ones (frequencies ranged from 5.4% to 50.4%). Only one non-synonymous coding region SNP (ncSNP), 808G>T in the exon 4, was observed among all the identified SNPs. Significant differences were observed in the renal clearance of metformin in subjects with different mutation status for this variant. The mean renal tubular clearance (CLt) values of metformin were 8.54 +/- 1.86, 7.72 +/- 0.64, and 6 36 +/- 0.98 ml/kg/min for subjects with GG (n = 6), GT (n = 5) and TT (n = 4) genotypes respectively (P = .043. 1-way ANOVA). After a 6-day cimetidine treatment, a mean decrease of 50.7%, 34.6% and 18.9% in metformin CLt was observed in the GG, GT and TT genotype groups (P =.013, P =.002 and P = .065 respectively compared to metformin alone). The decrease of CLt was significantly lower in the TT genotype group than that in the GG group (P = .027). Five SNPs were identified and 5 haplotypes inferred (frequencies ranged from 2.7% to 38.4%) in promoter/enhancer area. One haplotype, characterized by the presence of -1283 T>C, was associated with a significantly lower luciferase activity in vitro (26.7% decrease in comparison to wild-type, P = .016), but not with metformin CLt in Chinese Subjects. / Wang, Zhijun. / "Aug 2007." / Adviser: Moses Chow. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0966. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 148-168). / 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. / Abstracts in English and Chinese. / School code: 1307.

Thesis (Ph. D.)--University of Missouri--Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves : 212-236). Also available on the Internet.

published_or_final_version / abstract / Biochemistry / Master / Master of Philosophy

Thesis. 1975. Ph.D.--Massachusetts Institute of Technology. Dept. of Chemical Engineering. / Vita. / Includes bibliographical references. / Ph.D.

by Wong Wah-Kwan, Herman. / Thesis (M.Phil.)--Chinese University of Hong Kong. / Includes bibliographical references (leaves 69-79). / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Pregnancy-induced hypertension --- p.2 / Chapter 1.1a --- Definition of pregnancy-induced hypertension --- p.2 / Chapter 1.2 --- A brief history of pregnancy-induced hypertension --- p.5 / Chapter 1.3 --- The epidemiology of pregnancy-induced hypertension --- p.6 / Chapter 1.4 --- Prediction of pregnancy-induced hypertension --- p.8 / Chapter 1.5 --- Erythrocyte sodium-lithium countertransport --- p.14 / Chapter 1.5.1 --- The history and characteristics of SLC --- p.14 / Chapter 1.5.2 --- SLC in essential hypertension --- p.19 / Chapter 1.5.3 --- SLC in pregnancy --- p.26 / Chapter 1.5.4 --- SLC in other diseases --- p.27 / Chapter 1.6 --- Methods used in the study of erythrocyte SLC --- p.32 / Chapter 1.7 --- Aims of the projects --- p.34 / Chapter CHAPTER 2 --- MATERIALS & METHODS --- p.35 / Chapter 2.1 --- Anthropometric measurements --- p.36 / Chapter 2.1.1 --- Blood pressure measurements --- p.36 / Chapter 2.1.2 --- Physical measurements --- p.36 / Chapter 2.1.3 --- Gestational age --- p.36 / Chapter 2.2 --- Materials --- p.37 / Chapter 2.3 --- Method for the measurement of erythrocyte SLC --- p.37 / Chapter CHAPTER 3 --- PRECISION & INTRA-INDIVIDUAL VARIATION OF ERYTHROCYTE SLC IN MALES & FEMALES --- p.42 / Chapter 3.1 --- Assessment of the precision of the methods --- p.43 / Chapter 3.2 --- Method of study --- p.45 / Chapter 3.3 --- Statistics --- p.46 / Results --- p.47 / Chapter CHAPTER 4 --- PREDICTION OF PREGNANCY-INDUCED HYPERTENSION: SLC ACTIVITIES IN SECOND & THIRD TRIMESTERS --- p.54 / Chapter 4.1 --- Method of Study --- p.55 / Chapter 4.2 --- Results --- p.55 / Chapter CHAPTER 5 --- DISCUSSION --- p.63 / REFERENCES --- p.69

by Wai-on Fu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 88-95). / Chapter Chapter I --- Introduction --- p.1 / Chapter I .1 --- Structure and functions of the epididymis --- p.1 / Chapter I.2 --- Cellular mechanisms for electrolyte secretion --- p.3 / Chapter I.3 --- Second-messenger modulation of chloride secretion in epididymis --- p.5 / Chapter I.3.1 --- Cyclic AMP pathway --- p.5 / Chapter I.3.2 --- Ca2+ as second messenger --- p.6 / Chapter I.4 --- Pathophysiology of electrolyte transport in the epididymis --- p.6 / Chapter I.5 --- Objectives of the study --- p.9 / Chapter Chapter II. --- Materials and Methods --- p.10 / Chapter II. 1 --- Materials --- p.10 / Chapter II. 1.1 --- Culture media and enzyme --- p.10 / Chapter II. 1.2. --- Drugs --- p.10 / Chapter II. 1.3 --- Chemicals --- p.11 / Chapter II. 1.4. --- Animals and human tissue --- p.11 / Chapter II.2 --- Preparation of solutions --- p.12 / Chapter II. 3. --- Preparation of cultured cells --- p.12 / Chapter II.3 .1 --- Culture of rat epididymal epithelial cells --- p.12 / Chapter II.3.2 --- Cultured of human epididymal epithelial cells --- p.16 / Chapter II.4. --- Patch-Clamp technique --- p.21 / Chapter II.4.1 --- Electrode --- p.23 / Chapter II.4.2 --- Pulling of electrode --- p.23 / Chapter II.4.3 --- Coating of electrode --- p.23 / Chapter II.4.4 --- Polishing of the electrode --- p.24 / Chapter II.4.5 --- Filling of the electrodes --- p.26 / Chapter II.4.6 --- Mounting of Electrode to the Headstage Pipette Holder --- p.26 / Chapter II.4.7 --- Electrical Isolation --- p.28 / Chapter II.4.8 --- Vibration Isolation --- p.28 / Chapter II.4.9 --- "Formation of ""Giga-seal"" and Whole-cell configuration" --- p.28 / Chapter II.4.10 --- Correction for liquid junction potential --- p.30 / Chapter II.4.11 --- "Data Acquisition and Analyses," --- p.32 / Chapter II.4.12 --- Statistics --- p.34 / Chapter Chapter III. --- Results --- p.35 / Anion Secretion in human epididymal cells --- p.35 / Chapter III. 1 --- Whole-cell current in human epididymal cells --- p.35 / Chapter III. 2 --- Effect of adrenergic receptor blockers on whole-cell current --- p.38 / Chapter III.3 --- Effect of inhibitors of the cyclic AMP pathway --- p.42 / Chapter III.4 --- Effect of altering intracellular calcium concentration --- p.42 / Anion secretion in rat epididymal cells --- p.46 / Chapter III. 5 --- Effect of cAMP on whole cell C1- current in rat epididymis --- p.46 / Chapter III.6 --- Effect of ionomycin on whole cell C1- current --- p.53 / Chapter III.7 --- Differences between cAMP- and ionophore- dependent C1- current --- p.57 / Chapter III. 8 --- The swelling-induced whole-cell currents --- p.63 / Chapter III.9 --- The swelling-induced current was mainly C1- selective --- p.65 / Chapter III. 10 --- Anion selectivity of the swelling-induced C1- current --- p.68 / Chapter III. 11 --- Inhibition of the swelling-induced C1- conductance by anion channel blockers --- p.68 / Chapter III. 12 --- The role of Ca2+ and cAMP in swelling-induced C1- conductance --- p.74 / Chapter Chapter IV. --- Discussion --- p.79 / Signal transduction mechanism of adrenaline stimulated C1- current in human epididymal cell --- p.79 / Anion secretion in rat epididymal cell The role of Ca2+ and cAMP --- p.83 / Chapter Chapter V. --- Reference --- p.88

Ying Zheng. / Thesis submitted in: October 2001. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 84-90). / Abstracts in English and Chinese. / ABSTRACT --- p.ii / 中文摘要 --- p.iv / ACKNOWLEDGEMENTS --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF FIGURES --- p.x / LIST OF TABLES --- p.xii / ABBREVIATIONS --- p.xiii / Chapter CHAPTER 1. --- Introduction --- p.1 / Chapter 1.1. --- Rationale of the Study --- p.2 / Chapter 1.2. --- Flavonoids --- p.3 / Chapter 1.2.1. --- Introduction --- p.3 / Chapter 1.2.2. --- Potential Health Effects --- p.5 / Chapter 1.2.3. --- Absorption Studies --- p.6 / Chapter 1.3. --- Drug Absorption --- p.9 / Chapter 1.3.1. --- Pathways and Mechanisms of Intestinal Absorption --- p.9 / Chapter 1.3.2. --- Transporters Potentially Involved in the Absorption of Flavonoids --- p.11 / Chapter 1.3.2.1. --- Glucose Transporters --- p.11 / Chapter 1.3.2.2. --- Multidrug Resistance Systems --- p.13 / Chapter 1.3.2.2.1. --- P-glycoprotein --- p.13 / Chapter 1.3.2.2.2. --- Non-P-glycoprotein Efflux Mechanisms --- p.15 / Chapter 1.4. --- In vitro Models to Study Absorption --- p.15 / Chapter 1.4.1. --- Ussing Chamber --- p.16 / Chapter 1.4.2. --- Cultured Cells --- p.17 / Chapter 1.4.2.1. --- Choice of Cells --- p.17 / Chapter 1.4.2.2. --- Caco-2 Cell Monolayers as in vitro Model --- p.18 / Chapter 1.4.2.3. --- Correlation Between in vivo Absorption and in vitro Permeability Coefficients --- p.19 / Chapter 1.4.3. --- Everted Gut Sacs --- p.20 / Chapter 1.4.4. --- Brush Border Membrane Vesicles (BBMVs) --- p.20 / Chapter 1.4.5. --- In situ Experiments --- p.21 / Chapter 1.5. --- Aims and Scope of the Present Study --- p.23 / Chapter CHAPTER 2. --- Materials & Methods --- p.25 / Chapter 2.1. --- Materials --- p.26 / Chapter 2.1.1. --- Chemicals --- p.26 / Chapter 2.1.2. --- Materials for Cell Culture --- p.27 / Chapter 2.1.3. --- Instruments --- p.28 / Chapter 2.1.4. --- Animals --- p.28 / Chapter 2.2. --- Methods --- p.29 / Chapter 2.2.1. --- Preformulation Studies on Selected Flavonoids --- p.29 / Chapter 2.2.1.1. --- Determination of Stability --- p.29 / Chapter 2.2.1.2. --- Thermal Analysis --- p.29 / Chapter 2.2.1.3. --- Determination of Solubility --- p.29 / Chapter 2.2.1.4. --- Determination of Partition Coefficient --- p.30 / Chapter 2.2.2. --- Validation of in vitro Models --- p.30 / Chapter 2.2.2.1. --- Ussing Chamber --- p.30 / Chapter 2.2.2.1.1. --- Tissue Preparation --- p.30 / Chapter 2.2.2.1.2. --- Electrical Measurements --- p.31 / Chapter 2.2.2.1.3. --- Experimental Protocols --- p.31 / Chapter 2.2.2.1.4. --- Calculations of Permeability --- p.32 / Chapter 2.2.2.2. --- Caco-2 Cell Monolayers --- p.32 / Chapter 2.2.2.2.1. --- Preparation of Caco-2 Cell Monolayers --- p.32 / Chapter 2.2.2.2.2. --- Validation of Caco-2 Cell Monolayers --- p.32 / Chapter 2.2.2.2.3. --- Calculation of Permeability --- p.34 / Chapter 2.2.3. --- Transport Studies of Selected Flavonoids --- p.34 / Chapter 2.2.4. --- Brush Border Membrane Vesicles (BBMVs) --- p.35 / Chapter 2.2.4.1. --- Preparation of BBMVs --- p.35 / Chapter 2.2.4.2. --- Uptake of D-glucose by BBMVs --- p.38 / Chapter 2.2.4.3. --- Counting of 3H-D-glucose in BBMVs --- p.39 / Chapter 2.2.4.4. --- Calculation of Glucose Uptake --- p.39 / Chapter 2.2.4.5. --- Total Protein Assay --- p.40 / Chapter 2.2.5. --- Analytical Methods --- p.41 / Chapter 2.2.5.1. --- HPLC Analysis --- p.41 / Chapter 2.2.5.1.1. --- HPLC Analysis of Quercetin and Related Glycosides --- p.41 / Chapter 2.2.5.1.2. --- HPLC-MS Analysis of Degradation Products --- p.41 / Chapter 2.2.5.1.3. --- HPLC Analysis of Propranolol --- p.42 / Chapter 2.2.5.2. --- UV Analysis --- p.42 / Chapter 2.2.5.3. --- Fluorescence Analysis --- p.42 / Chapter 2.2.5.4. --- Analysis of Radiolabeled Markers --- p.42 / Chapter 2.2.6. --- Statistical Analysis --- p.42 / Chapter CHAPTER 3. --- Results & Discussions --- p.44 / Chapter 3.1. --- Preformulation Studies on Selected Flavonoids --- p.45 / Chapter 3.1.1. --- Stability --- p.45 / Chapter 3.1.2. --- Thermal Analysis --- p.52 / Chapter 3.1.3. --- Aqueous Solubility --- p.58 / Chapter 3.1.4. --- Partition Coefficient --- p.61 / Chapter 3.2. --- Validation of in vitro Models --- p.62 / Chapter 3.2.1. --- Selection of Marker Compounds --- p.62 / Chapter 3.2.2. --- Validation of Ussing Chamber --- p.63 / Chapter 3.2.3. --- Validation of Caco-2 Cell Monolayers --- p.64 / Chapter 3.2.3.1. --- Integrity of Caco-2 Cell Monolayers --- p.64 / Chapter 3.2.3.2. --- Permeabilities of Marker Compounds --- p.65 / Chapter 3.2.3.3. --- Selection of in vitro Models --- p.66 / Chapter 3.2.3.3. --- Validation of Sodium/Glucose Cotransporter (SGLT1) --- p.66 / Chapter 3.3. --- Transport Studies of Quercetin and Related Flavonoids --- p.67 / Chapter 3.3.1. --- Direction of Transport --- p.67 / Chapter 3.3.2. --- Concentration Dependence --- p.69 / Chapter 3.3.3. --- Inhibition of P-gp by Verapamil --- p.71 / Chapter 3.3.4. --- Metabolism of Quercetin in Caco-2 Cells --- p.72 / Chapter 3.3.5. --- Studies of Quercetin-3-glucoside with Sugar Transporters --- p.73 / Chapter 3.4. --- Uptake of D-glucose by Brush Border Membrane Vesicles (BBMVs) --- p.75 / Chapter CHAPTER 4. --- Conclusions --- p.80 / References --- p.83

Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Includes bibliographical references. / by Frank Glenroy Smith, III. / Sc.D.