Thesis (M.D.)--University of Hong Kong, 1959. / Type written copy. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.D.)--University of Hong Kong, 1959. / Includes bibliography. Also available in print.

No description available.

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The effects of di-2 ethylhexyl phthalate (DEHP) over periods of 3 days to 9 months were examined in both male and female rats using biochemical, histological and ultrastructural techniques. Responses occurred in a characteristic order. Initial effects included : changes in the. distribution of lipid in the liver, proliferation of hepatic peroxisomes and induction of laurate hydroxylases. More slowly developing changes were (1) hypertrophy of the hepatocytes, (2) centrilobular loss of glycogen and (3) a fall in glucose-6-phosphatase activity. After 9 months of treatment, accumulation of lipid-loaded lysosomes were observed. All these changes were observed in rats treated with 1000 or 200 mg/kg/day of DEHP, but rats treated with 50 mg/kg/day of DEHP did not show the later changes. In addition to these sustained alterations, two transient changes were observed. Male rats, treated with 1000 mg/kg/day of DEHP showed changes in the biliary system as shown by electron microscopy, by examination of bile flow, bile enzymes and proteins. Furthermore, a burst of mitosis occurred immediately after commencement of treatment of DEHP, the magnitude and time of which was dose-dependent. Changes in female rats were qualitatively similar, but quantitatively smaller, than in male rats. Mature male rats treated for 3 or 13 days with either DEHP or the hypolipidaemic drugs fenofibrate or clofibrate, showed similar changes to young rats with the exception of the mitotic burst which did not occur in these animals. The initial short term effects of DEHP and the straight chain analogues, di-n-octyl phthalate (DN0P) and di-n- hexyl phthalate (DNHP) in vivo and their respective esters, MEHP and MNHP, were reproduced in cultured hepatocytes. There was induction of peroxisomal enzymes in response to treatment with DEHP or MEHP but little or no induction after treatment with DNOP, MNOP or MNHP. Accumulation of lipid was seen after 24 hours of treatment With MEHP, MNOP and MNHP. However, the mitotic burst was not reproduced in cultured hepatocytes treated with MEHP, neither was there a fall in glucose-6-phosphatase activity. There was no increase in H[2]O[2] production either in vitro in cultured hepatocytes treated with MEHP, or in vivo as measured by catalase compound I in perfused liver from rats treated with DEHP in the diet. There was no evidence for mutagenic activity of DEHP or MEHP in the Ames Test. Treatment of isolated hepatocytes with MEHP, straight chain phthalate esters or clofibrate, resulted in early marked pertubations in lipid metabolism, namely, an increase in production of neutral fats and generally in fatty acid oxidation. This may explain the increased storage of lipid, in the liver. There was a marked difference in response between hepatocytes isolated from fed and fasted rats, the latter being more sensitive to all compounds. Indeed with fed rats there was, in some cases, a slight decrease in fatty acid oxidation. The effects on lipid metabolism were observed at concentrations which produced peroxisome proliferation in cultured cells.

Lo Kam Chun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 310-323). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese version) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Abbreviations --- p.xxvi / List of Unit Abbreviations --- p.xxviii / List of Figures --- p.xxix / List of Tables --- p.xxxviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.3 / Chapter 2.1 --- Peroxisome proliferator-activated receptors (PPARs) --- p.3 / Chapter 2.1.1 --- Structure of PPAR --- p.4 / Chapter 2.1.2 --- Ligands of PPAR --- p.6 / Chapter 2.1.3 --- Peroxisome proliferator responsive elements (PPREs) --- p.8 / Chapter 2.1.4 --- Coactivators and corepressors of PPAR --- p.8 / Chapter 2.1.5 --- Signaling cross-talk between PPAR and other nuclear hormone receptors --- p.11 / Chapter 2.1.6 --- Tissue distribution of PPAR --- p.12 / Chapter 2.2 --- PPARα and lipid metabolism --- p.13 / Chapter 2.3 --- "PPARα, cholesterol and lipoprotein metabolism" --- p.18 / Chapter 2.4 --- PPARα and glucose metabolism --- p.20 / Chapter 2.5 --- PPARα and amino acid metabolism --- p.21 / Chapter 2.6 --- "PPARα, atherosclerosis and inflammation" --- p.21 / Chapter 2.7 --- PPARα and epidermal differentiation --- p.23 / Chapter 2.8 --- PPARα and peroxisome proliferator-induced liver injury --- p.24 / Chapter Chapter 3 --- Objectives --- p.25 / Chapter Chapter 4 --- Materials and Methods --- p.26 / Chapter 4.1 --- Animal tail-genotyping --- p.26 / Chapter 4.1.1 --- Materials --- p.26 / Chapter 4.1.2 --- Methods --- p.26 / Chapter 4.2 --- Animal treatment --- p.29 / Chapter 4.2.1 --- Animals --- p.30 / Chapter 4.2.2 --- Treatment --- p.30 / Chapter 4.3 --- "Serum β-hydroxybutyrate, triglyceride and cholesterol analyses" --- p.30 / Chapter 4.3.1 --- Materials --- p.32 / Chapter 4.3.2 --- Methods --- p.32 / Chapter 4.3.2.1 --- Serum preparation --- p.32 / Chapter 4.3.2.2 --- β-hydroxybutyrate determination --- p.32 / Chapter 4.3.2.3 --- Triglyceride determination --- p.33 / Chapter 4.3.2.4 --- Cholesterol determination --- p.33 / Chapter 4.4 --- Total RNA isolation --- p.34 / Chapter 4.4.1 --- Materials --- p.34 / Chapter 4.4.2 --- Methods --- p.34 / Chapter 4.5 --- DNase I treatment --- p.35 / Chapter 4.5.1 --- Materials --- p.35 / Chapter 4.5.2 --- Methods --- p.35 / Chapter 4.6 --- Reverse transcription (RT) and non-fluorescent PCR (non-fluoroDD PCR) --- p.36 / Chapter 4.6.1 --- Materials --- p.41 / Chapter 4.6.2 --- Methods --- p.41 / Chapter 4.7 --- Reverse transcription (RT) and fluorescent PCR (fluoroDD PCR) --- p.42 / Chapter 4.7.1 --- Materials --- p.42 / Chapter 4.7.2 --- Methods --- p.42 / Chapter 4.8 --- Fluorescent differential display --- p.42 / Chapter 4.8.1 --- Materials --- p.43 / Chapter 4.8.2 --- Methods --- p.43 / Chapter 4.9 --- Excision of differentially expressed cDNA fragments --- p.44 / Chapter 4.9.1 --- Materials --- p.44 / Chapter 4.9.2 --- Methods --- p.44 / Chapter 4.10 --- Reamplification of excised cDNA fragments --- p.44 / Chapter 4.10.1 --- Materials --- p.45 / Chapter 4.10.2 --- Methods --- p.45 / Chapter 4.11 --- Subcloning of reamplified cDNA fragments --- p.46 / Chapter 4.11.1 --- Materials --- p.46 / Chapter 4.11.2 --- Methods --- p.46 / Chapter 4.12 --- Reverse dot blot analysis of subcloned cDNA fragments --- p.50 / Chapter 4.12.1 --- Materials --- p.50 / Chapter 4.12.2 --- Methods --- p.51 / Chapter 4.12.2.1 --- Mini-preparation of plasmid DNA from recombinant clones ´ؤ´ؤalkaline lysis method --- p.51 / Chapter 4.12.2.2 --- Dot blot preparation --- p.52 / Chapter 4.12.2.3 --- cDNA library and probe preparation --- p.52 / Chapter 4.12.2.4 --- Hybridization and signal detection --- p.54 / Chapter 4.13 --- Sequencing of reverse dot blot-confirmed cDNA fragments --- p.55 / Chapter 4.13.1 --- Materials --- p.55 / Chapter 4.13.2 --- Methods --- p.55 / Chapter 4.13.2.1 --- Mini-preparation of plasmid DNA from recombinant clones ´ؤ´ؤQiagen method --- p.55 / Chapter 4.13.2.2 --- DNA sequencing by CEQ dye terminator cycle sequencing --- p.56 / Chapter 4.13.2.3 --- BLAST search against computer database --- p.57 / Chapter 4.14 --- Northern blot analysis of sequenced cDNA fragments --- p.57 / Chapter 4.14.1 --- Materials --- p.58 / Chapter 4.14.2 --- Methods --- p.58 / Chapter 4.14.2.1 --- Midi-preparation of plasmid DNA from recombinant clones for probe preparation ´ؤ´ؤQiagen method --- p.58 / Chapter 4.14.2.2 --- DIG-labeled cDNA probe preparation --- p.59 / Chapter 4.14.2.3 --- Formaldehyde-agarose gel electrophoresis --- p.60 / Chapter 4.14.2.4 --- Hybridization and signal detection --- p.61 / Chapter Chapter 5 --- Results --- p.63 / Chapter 5.1 --- Confirmation of genotypes by PCR tail-genotyping --- p.63 / Chapter 5.2 --- Morphological observation --- p.63 / Chapter 5.3 --- "Serum β-hydroxybutyrate, triglyceride and cholesterol levels" --- p.67 / Chapter 5.4 --- RT and non-fluoroDD PCR --- p.69 / Chapter 5.5 --- RT and fluoroDD PCR --- p.94 / Chapter 5.6 --- Reamplification of cDNA fragments --- p.121 / Chapter 5.7 --- Subcloning of reamplified cDNA fragments --- p.131 / Chapter 5.8 --- Reverse dot blot analysis of subcloned cDNA fragments --- p.174 / Chapter 5.9 --- Sequencing of reverse dot blot-confirmed cDNA fragments --- p.243 / Chapter 5.10 --- Northern blot analysis of sequenced cDNA fragments --- p.262 / Chapter Chapter 6 --- Discussions --- p.282 / Chapter 6.1 --- PPARα and hepatic lipid metabolism during fasting --- p.282 / Chapter 6.2 --- Enlargement of liver in starved PPARα-null mice --- p.283 / Chapter 6.3 --- "Alteration of serum β-hydroxybutyrate, triglyceride and cholesterol levels by PPARa during fasting" --- p.284 / Chapter 6.4 --- Identification of PPARα-dependent and fasting- responsive genes by fluorescent differential display and PPARα-null mice --- p.285 / Chapter 6.4.1 --- Roles of PPARα-dependent and fasting-responsive genes --- p.289 / Chapter 6.4.1.1 --- Lipid metabolism --- p.290 / Chapter 6.4.1.2 --- Protein metabolism --- p.299 / Chapter 6.4.1.3 --- Other functions --- p.302 / Chapter Chapter 7 --- Conclusions --- p.307 / Chapter Chapter 8 --- Future Studies --- p.309 / Chapter 8.1 --- Further identification of fasting-responsive and PPARα- dependent genes --- p.309 / Chapter 8.2 --- Characterization of the mouse EST --- p.309 / References --- p.310 / Chapter Appendix A: --- Protocol for reaction preparation / Chapter Table A1 --- PCR-tail genotyping --- p.324 / Chapter Table A2 --- DNase I treatment of total RNA --- p.324 / Chapter Table A3 --- Reverse transcription (RT) for both non-fluoroDD and fluooDD PCR --- p.324 / Chapter Table A4 --- Non-fluoroDD PCR --- p.325 / Chapter Table A5 --- FluoroDD PCR --- p.325 / Chapter Table A6 --- Reamplification of cDNA fragments --- p.325 / Chapter Table A7 --- Reverse transcription in cDNA library synthesis for reverse dot blot analysis --- p.326 / Chapter Table A8 --- RT-PCR in cDNA library synthesis for reverse dot blot analysis --- p.326 / Chapter Appendix B: --- Phenol-chloroform extraction for recombinant subclones / Chapter Figure B1 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel D --- p.327 / Chapter Figure B2 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel E --- p.328 / Chapter Figure B3 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gels G and HH --- p.329 / Chapter Figure B4 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel JJ --- p.330 / Chapter Figure B5 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel LL --- p.331 / Chapter Figure B6 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel MM --- p.332 / Chapter Figure B7 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gels NN and OO (fragments OO1 - OO4) --- p.333 / Chapter Figure B8 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel 00 (fragments OO5 - OO7) --- p.334 / Chapter Figure B9 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel OO (fragments OO8 and OO9) --- p.335 / Chapter Figure B10 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel PP --- p.336 / Chapter Figure B11 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel QQ (fragments QQ1 and QQ3) --- p.337 / Chapter Figure B12 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel QQ (fragments QQ4 - QQ6) --- p.338 / Chapter Figure B13 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel RR --- p.339 / Chapter Figure B14 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gels SS and TT --- p.340 / Chapter Figure B15 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel UU --- p.341 / Chapter Figure B16 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel VV --- p.342 / Chapter Figure B17 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel WW --- p.343 / Chapter Figure B18 --- Phenol-chloroform extraction for recombinant subclones containing cDNA fragments excised from fluoroDD gel XX --- p.344 / Chapter Appendix C: --- DNA sequence and sequence alignment of cDNA subclones / Chapter C1.1 --- DNA sequence of cDNA subclone Dl#2 using Ml3 forward -20 primer and the sequence of 3´ة-AP3 --- p.345 / Chapter C1.2 --- Sequence alignment of cDNA subclone Dl#2 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.345 / Chapter C1.3 --- Summary of sequence alignment of cDNA subclone Dl#2 with mouse CYP4A10 --- p.345 / Chapter C2.1 --- DNA sequence of cDNA subclone Dl#2 using Ml3 reverse primer and the sequence of 5´ة-ARP12 --- p.346 / Chapter C2.2 --- Sequence alignment of cDNA subclone Dl#2 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.346 / Chapter C2.3 --- Summary of sequence alignment of cDNA subclone Dl#2 with mouse CYP4A10 --- p.346 / Chapter C3.1 --- DNA sequence of cDNA subclone D2#9 using Ml3 forward -20 primer and the sequence of 5'-ARP12 --- p.347 / Chapter C3.2 --- Sequence alignment of cDNA subclone D2#9 with mouse Bhmt by BLAST searching with the National Center for Biotechnology Information database --- p.347 / Chapter C3.3 --- Summary of sequence alignment of cDNA subclone D2#9 with mouse Bhmt --- p.347 / Chapter C4.1 --- DNA sequence of cDNA subclone D3#3 using Ml3 forward -20 primer and the sequence of 5'-ARP12 --- p.348 / Chapter C4.2 --- Sequence alignment of cDNA subclone D3#3 with mouse hypothetical protein MMT-7 by BLAST searching with the National Center for Biotechnology Information database --- p.348 / Chapter C4.3 --- Summary of sequence alignment of cDNA subclone D3#3 with mouse hypothetical protein MMT-7 --- p.348 / Chapter C5.1 --- DNA sequence of cDNA subclone D3#3 using M13 reverse primer and the sequence of 3´ة-AP3 --- p.349 / Chapter C5.2 --- Sequence alignment of cDNA subclone D3#3 with mouse hypothetical protein MMT-7 by BLAST searching with the National Center for Biotechnology Information database --- p.349 / Chapter C5.3 --- Summary of sequence alignment of cDNA subclone D3#3 with mouse hypothetical protein MMT-7 --- p.349 / Chapter C6.1 --- DNA sequence of cDNA subclone LL1#7 using Ml3 reverse primer and the sequence of 3´ة-AP4 --- p.350 / Chapter C6.2 --- Sequence alignment of cDNA subclone LL1#7 with mouse Ctsl by BLAST searching with the National Center for Biotechnology Information database --- p.350 / Chapter C6.3 --- Summary of sequence alignment of cDNA subclone LL1#7 with mouse Ctsl --- p.350 / Chapter C7.1 --- DNA sequence of cDNA subclone LL1#11 using Ml3 forward -20 primer and the sequence of 5'-ARP6 --- p.351 / Chapter C7.2 --- Sequence alignment of cDNA subclone LL1#11 with mouse Ctsl by BLAST searching with the National Center for Biotechnology Information database --- p.351 / Chapter C7.3 --- Summary of sequence alignment of cDNA subclone LL1#11 with mouse Ctsl --- p.351 / Chapter C8.1 --- DNA sequence of cDNA subclone MM1#1 using M13 forward -20primer and the sequence of 3'-AP2 --- p.352 / Chapter C8.2 --- Sequence alignment of cDNA subclone MM1#1 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.352 / Chapter C8.3 --- Summary of sequence alignment of cDNA subclone MM1#1 with mouse CYP4A10 --- p.352 / Chapter C9.1 --- DNA sequence of cDNA subclone MM1#1 using Ml3 reverse primer and the sequence of 5´ة-ARP7 --- p.353 / Chapter C9.2 --- Sequence alignment of cDNA subclone MM1#1 with mouse CYP4A110 by BLAST searching with the National Center for Biotechnology Information database --- p.353 / Chapter C9.3 --- Summary of sequence alignment of cDNA subclone MM1#1 with mouse CYP4A10 --- p.353 / Chapter C10.1 --- DNA sequence of cDNA subclone 002#6 using Ml3 forward -20 primer and the sequence of 3'-AP9 --- p.354 / Chapter C10.2 --- Sequence alignment of cDNA subclone 002#6 with rat ASL by BLAST searching with the National Center for Biotechnology Information database --- p.354 / Chapter C10.3 --- Summary of sequence alignment of cDNA subclone 002#6 with rat ASL --- p.354 / Chapter C11.l --- DNA sequence of cDNA subclone 002#9 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.355 / Chapter C11.2 --- Sequence alignment of cDNA subclone 002#9 with rat ASL by BLAST searching with the National Center for Biotechnology Information database --- p.355 / Chapter C11.3 --- Summary of sequence alignment of cDNA subclone 002#9 with rat ASL --- p.355 / Chapter C12.1 --- DNA sequence of cDNA subclone 003#4 using Ml3 forward -20 primer and the sequence of 5'-ARP3 --- p.356 / Chapter C12.2 --- Sequence alignment of cDNA subclone O03#4 with mouse Phyh by BLAST searching with the National Center for Biotechnology Information database --- p.356 / Chapter C12.3 --- Summary of sequence alignment of cDNA subclone 003#4 with mouse Phyh --- p.356 / Chapter C13.1 --- DNA sequence of cDNA subclone 003#9 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.357 / Chapter C13.2 --- Sequence alignment of cDNA subclone 003#9 with rat ASL by BLAST searching with the National Center for Biotechnology Information database --- p.357 / Chapter C13.3 --- Summary of sequence alignment of cDNA subclone 003#9 with rat ASL --- p.357 / Chapter C14. --- DNA sequence of cDNA subclone 004#3 using M13 forward -20 primer and the sequence of 5'-ARP3 --- p.358 / Chapter C14.2 --- Sequence alignment of cDNA subclone 004#3 with rat ASL by BLAST searching with the National Center for Biotechnology Information database --- p.358 / Chapter C14.3 --- Summary of sequence alignment of cDNA subclone 004#3 with rat ASL --- p.358 / Chapter C15.1 --- DNA sequence of cDNA subclone 004#3 using Ml3 reverse primer and the sequence of 3'-AP9 --- p.359 / Chapter C15.2 --- Sequence alignment of cDNA subclone 004#3 with rat ASL by BLAST searching with the National Center for Biotechnology Information database --- p.359 / Chapter C15.3 --- Summary of sequence alignment of cDNA subclone 004#3 with rat ASL --- p.359 / Chapter C16.1 --- DNA sequence of cDNA subclone 004#4 using Ml 3 forward -20primer and the sequence of 5?-ARP3 --- p.360 / Chapter C16.2 --- Sequence alignment of cDNA subclone 004#4 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.360 / Chapter C16.3 --- Summary of sequence alignment of cDNA subclone 004#4 with mouse CYP4A14 --- p.360 / Chapter C17.1 --- DNA sequence of cDNA subclone 004#4 using M13 reverse primer and the sequence of 3´ة-AP9 --- p.361 / Chapter C17.2 --- Sequence alignment of cDNA subclone 004#4 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.361 / Chapter C17.3 --- Summary of sequence alignment of cDNA subclone 004#4 with mouse CYP4A14 --- p.361 / Chapter C18.1 --- DNA sequence of cDNA subclone 004#10 using M13 forward -20primer and the sequence of 3´ة-AP9 --- p.362 / Chapter C18.2 --- a Sequence alignment of cDNA subclone 004#10 with rat PBE by BLAST searching with the National Center for Biotechnology Information database --- p.362 / Chapter C18.3 --- a Summary of sequence alignment of cDNA subclone 004#10 with rat PBE --- p.362 / Chapter C18.2 --- b Sequence alignment of cDNA subclone 004#10 with mouse L-PBE by BLAST searching with the National Center for Biotechnology Information database --- p.363 / Chapter C18.3 --- b Summary of sequence alignment of cDNA subclone 004#10 with mouse L-PBE --- p.363 / Chapter C19.1 --- DNA sequence of cDNA subclone 005#13 using M13 forward -20primer and the sequence of 3'-AP9 --- p.364 / Chapter C19.2 --- Sequence alignment of cDNA subclone 005#13 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.364 / Chapter C19.3 --- Summary of sequence alignment of cDNA subclone 005#13 with mouse CYP4A14 --- p.364 / Chapter C20.1 --- DNA sequence of cDNA subclone 005#13 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.365 / Chapter C20.2 --- Sequence alignment of cDNA subclone 005#13 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.365 / Chapter C20.3 --- Summary of sequence alignment of cDNA subclone 005#13 with mouse CYP4A14 --- p.365 / Chapter C21.1 --- DNA sequence of cDNA subclone 006#2 using Ml3 forward -20 primer and the sequence of 3´ة-AP9 --- p.366 / Chapter C21.2 --- Sequence alignment of cDNA subclone 006#2 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.366 / Chapter C21.3 --- Summary of sequence alignment of cDNA subclone 006#2 with mouse CYP4A14 --- p.366 / Chapter C22.1 --- DNA sequence of cDNA subclone 006#8 using Ml3 forward -20 primer and the sequence of 5'-ARP3 --- p.367 / Chapter C22.2 --- Sequence alignment of cDNA subclone 006#8 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.367 / Chapter C22.3 --- Summary of sequence alignment of cDNA subclone 006#8 with mouse CYP4A14 --- p.367 / Chapter C23.1 --- DNA sequence of cDNA subclone 006#10 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.368 / Chapter C23.2 --- Sequence alignment of cDNA subclone 006#10 with mouse CYP4A14 by BLAST searching with the National --- p.368 / Chapter C23.3 --- Summary of sequence alignment of cDNA subclone 006#10 with mouse CYP4A14 --- p.368 / Chapter C24.1 --- DNA sequence of cDNA subclone 007#6 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.368 / Chapter C24.2 --- Sequence alignment of cDNA subclone 007#6 with mouse Spil-3 by BLAST searching with the National Center for Biotechnology Information database --- p.369 / Chapter C24.3 --- Summary of sequence alignment of cDNA subclone 007#6 with mouse Spil-3 --- p.369 / Chapter C25.1 --- DNA sequence of cDNA subclone 007#10 using Ml3 forward -20 primer and the sequence of 3'-AP9 --- p.370 / Chapter C25.2 --- Sequence alignment of cDNA subclone 007#10 with mouse Spil-3 by BLAST searching with the National Center for Biotechnology Information database --- p.370 / Chapter C25.3 --- Summary of sequence alignment of cDNA subclone 007#10 with mouse Spil-3 --- p.370 / Chapter C26.1 --- DNA sequence of cDNA subclone 008#10 using Ml3 forward -20 primer and the sequence of 5'-ARP3 --- p.371 / Chapter C26.2 --- Sequence alignment of cDNA subclone 008#10 with mouse Hpcl by BLAST searching with the National Center for Biotechnology Information database --- p.371 / Chapter C26.3 --- Summary of sequence alignment of cDNA subclone 008#l0 with mouse Hpcl --- p.371 / Chapter C27.1 --- DNA sequence of cDNA subclone 009#6 using Ml3 forward -20 primer and the 3´ة-AP9 --- p.372 / Chapter C27.2 --- Sequence alignment of cDNA subclone 009#6 with mouse Hpcl by BLAST searching with the National Center for Biotechnology Information database --- p.372 / Chapter C27.3 --- Summary of sequence alignment of cDNA subclone 009#6 with mouse Hpcl --- p.372 / Chapter C28.1 --- DNA sequence of cDNA subclone 009#8 using Ml3 reverse primer and the sequence of 3'-AP9 --- p.373 / Chapter C28.2 --- Sequence alignment of cDNA subclone 009#8 with mouse Hpcl by BLAST searching with the National Center for Biotechnology Information database --- p.373 / Chapter C28.3 --- Summary of sequence alignment of cDNA subclone 009#8 with mouse Hpcl --- p.373 / Chapter C29.1 --- DNA sequence of cDNA subclone PP3#3 using M13 forward -20 primer and the sequence of 5'-ARP3 --- p.374 / Chapter C29.2 --- Sequence alignment of cDNA subclone PP3#3 with mouse CYP4A14 by BLAST searching with the National Center --- p.374 / Chapter C29.3 --- Summary of sequence alignment of cDNA subclone PP3#3 with mouse CYP4A14 --- p.374 / Chapter C30.1 --- DNA sequence of cDNA subclone PP3#13 using Ml3 reverse primer and the sequence of 5'-ARP3 --- p.375 / Chapter C30.2 --- Sequence alignment of cDNA subclone PP3#13 with mouse CYP4A14 by BLAST searching with the National Center for Biotechnology Information database --- p.375 / Chapter C30.3 --- Summary of sequence alignment of cDNA subclone PP3#13 with mouse CYP4A14 --- p.375 / Chapter C31.1 --- DNA sequence of cDNA subclone QQ4#14 using Ml3 forward -20 primer and the sequence of 5´ة-ARP2 --- p.376 / Chapter C31.2 --- Sequence alignment of cDNA subclone QQ4#14 with mouse MCAD by BLAST searching with the National Center for Biotechnology Information database --- p.376 / Chapter C31.3 --- Summary of sequence alignment of cDNA subclone QQ4#14 with mouse MCAD --- p.376 / Chapter C32.1 --- DNA sequence of cDNA subclone QQ4#15 using Ml3 reverse primer and the sequence of 5´ة-ARP2 --- p.377 / Chapter C32.2 --- Sequence alignment of cDNA subclone QQ4#15 with mouse MCAD by BLAST searching with the National Center for Biotechnology Information database --- p.377 / Chapter C32.3 --- Summary of sequence alignment of cDNA subclone QQ4#15 with mouse MCAD --- p.377 / Chapter C33.1 --- DNA sequence of cDNA subclone QQ5#14 using Ml3 forward -20 primer and the sequence of 3'-AP3 --- p.377 / Chapter C33.2 --- Sequence alignment of cDNA subclone QQ5#14 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.378 / Chapter C33.3 --- Summary of sequence alignment of cDNA subclone QQ5#14 with mouse MUP II --- p.378 / Chapter C34.1 --- DNA sequence of cDNA subclone QQ5#17 using Ml3 reverse primer and the sequence of 5'-ARP2 --- p.378 / Chapter C34.2 --- Sequence alignment of cDNA subclone QQ5#17 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.379 / Chapter C34.3 --- Summary of sequence alignment of cDNA subclone QQ5#17 with mouse MUP II --- p.379 / Chapter C35.1 --- DNA sequence of cDNA subclone QQ6#13 using Ml3 forward -20 primer and the sequence of 3'-AP3 --- p.380 / Chapter C35.2 --- Sequence alignment of cDNA subclone QQ6#13 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.380 / Chapter C35.3 --- Summary of sequence alignment of cDNA subclone QQ6#13 with mouse MUP II --- p.380 / Chapter C36.1 --- DNA sequence of cDNA subclone QQ6#14 using M13 reverse primer and the 5'-ARP2 --- p.381 / Chapter C36.2 --- Sequence alignment of cDNA subclone QQ6#14 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.381 / Chapter C36.3 --- Summary of sequence alignment of cDNA subclone QQ6#14 with mouse MUP II --- p.381 / Chapter C37.1 --- DNA sequence of cDNA subclone TT4#5 using Ml3 forward -20 primer and the sequence of 3´ة-AP5 --- p.382 / Chapter C37.2 --- Sequence alignment of cDNA subclone TT4#5 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.382 / Chapter C37.3 --- Summary of sequence alignment of cDNA subclone TT4#5 with mouse MUP II --- p.382 / Chapter C38.1 --- DNA sequence of cDNA subclone TT4#8 using Ml3 forward -20 primer and the sequence of 5´ة-ARP2 --- p.383 / Chapter C38.2 --- Sequence alignment of cDNA subclone TT4#8 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.383 / Chapter C38.3 --- Summary of sequence alignment of cDNA subclone TT4#8 with mouse MUP II --- p.383 / Chapter C39.1 --- DNA sequence of cDNA subclone TT4#9 using Ml3 reverse primer and the sequence of 3'-AP5 --- p.384 / Chapter C39.2 --- Sequence alignment of cDNA subclone TT4#9 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.384 / Chapter C39.3 --- Summary of sequence alignment of cDNA subclone TT4#9 with mouse MUP II --- p.384 / Chapter C40.1 --- DNA sequence of cDNA subclone TT5#1 using Ml3 forward -20 primer and the sequence of 5'-ARP2 --- p.385 / Chapter C40.2 --- Sequence alignment of cDNA subclone TT5#1 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.385 / Chapter C40.3 --- Summary of sequence alignment of cDNA subclone TT5#1 with mouse MUP II --- p.385 / Chapter C41.1 --- DNA sequence of cDNA subclone TT5#9 using Ml3 reverse primer and the sequence of 3´ة-AP5 --- p.386 / Chapter C41.2 --- Sequence alignment of cDNA subclone TT5#9 with mouse MUP II by BLAST searching with the National Center for Biotechnology Information database --- p.386 / Chapter C41.3 --- Summary of sequence alignment of cDNA subclone TT5#9 with mouse MUP II --- p.386 / Chapter C42.1 --- DNA sequence of cDNA subclone UU1#1 using Ml3 forward -20 primer and the sequence of 3´ة-AP2 --- p.387 / Chapter C42.2 --- Sequence alignment of cDNA subclone UU1#1 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.387 / Chapter C42.3 --- Summary of sequence alignment of cDNA subclone UU1#1 with mouse CYP4A10 --- p.387 / Chapter C43.1 --- DNA sequence of cDNA subclone UU1#4 using Ml3 reverse primer and the sequence of 5'-ARP12 --- p.388 / Chapter C43.2 --- Sequence alignment of cDNA subclone UU1#4 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.388 / Chapter C43.3 --- Summary of sequence alignment of cDNA subclone UU1#4 with mouse CYP4A10 --- p.388 / Chapter C44.1 --- DNA sequence of cDNA subclone VV5#2 using Ml3 forward -20 primer and the sequence of 3´ة-AP2 --- p.389 / Chapter C44.2 --- Sequence alignment of cDNA subclone VV5#2 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.389 / Chapter C44.3 --- Summary of sequence alignment of cDNA subclone VV5#2 with mouse CYP4A10 --- p.389 / Chapter C45.1 --- DNA sequence of cDNA subclone VV5#3 using Ml3 forward -20 primer and the sequence of 3'-AP2 --- p.390 / Chapter C45.2 --- Sequence alignment of cDNA subclone VV5#3 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.390 / Chapter C45.3 --- Summary of sequence alignment of cDNA subclone VV5#3 with mouse CYP4A10 --- p.390 / Chapter C46.1 --- DNA sequence of cDNA subclone VV5#4 using Ml3 reverse primer and the sequence of 5'-ARP18 --- p.391 / Chapter C46.2 --- Sequence alignment of cDNA subclone VV5#4 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.391 / Chapter C46.3 --- Summary of sequence alignment of cDNA subclone VV5#4 with mouse CYP4A10 --- p.391 / Chapter C47.1 --- DNA sequence of cDNA subclone VV8#5 using M13 forward -20 primer and the sequence of 5'-ARP18 --- p.392 / Chapter C47.2 --- Sequence alignment of cDNA subclone VV8#5 with mouse HMG-CoAS by BLAST searching with the National Center for Biotechnology Information database --- p.392 / Chapter C47.3 --- Summary of sequence alignment of cDNA subclone VV8#5 with mouse HMG-CoAS --- p.392 / Chapter C48.1 --- DNA sequence of cDNA subclone VV8#6 using Ml 3 reverse primer and the sequence of 3'-AP2 --- p.393 / Chapter C48.2 --- Sequence alignment of cDNA subclone VV8#6 with mouse HMG-CoAS by BLAST searching with the National Center for Biotechnology Information database --- p.393 / Chapter C48.3 --- Summary of sequence alignment of cDNA subclone VV8#6 with mouse HMG-CoAS --- p.393 / Chapter C49.1 --- DNA sequence of cDNA subclone WW1#3 using Ml 3 forward -20 primer and the sequence of 3'-AP2 --- p.394 / Chapter C49.2 --- Sequence alignment of cDNA subclone WW1#3 with mouse Spil-3 by BLAST searching with the National Center for Biotechnology Information database --- p.394 / Chapter C49.3 --- Summary of sequence alignment of cDNA subclone WW1#3 with mouse Spil-3 --- p.394 / Chapter C50.1 --- DNA sequence of cDNA subclone WW1#4 using Ml3 forward -20 primer and the sequence of 3'-AP2 --- p.395 / Chapter C50.2 --- Sequence alignment of cDNA subclone WW1#4 with mouse Spil-3 by BLAST searching with the National Center for Biotechnology Information database --- p.395 / Chapter C50.3 --- Summary of sequence alignment of cDNA subclone WW1#4 with mouse Spil-3 --- p.395 / Chapter C51.1 --- DNA sequence of cDNA subclone WW1#7 using M13 reverse primer and the sequence of 5´ة-ARP19 --- p.396 / Chapter C51.2 --- Sequence alignment of cDNA subclone WW1#7 with mouse Spil-3 by BLAST searching with the National Center for Biotechnology Information database --- p.396 / Chapter C51.3 --- Summary of sequence alignment of cDNA subclone WW1#7 ith mouse Spil-3 --- p.396 / Chapter C52.1 --- DNA sequence of cDNA subclone XX1#2 using Ml3 forward 20 primer and the sequence of 3´ة-APl0 --- p.397 / Chapter C52.2 --- Sequence alignment of cDNA subclone XX1#2 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.397 / Chapter C52.3 --- Summary of sequence alignment of cDNA subclone XX1#2 with mouse CYP4A10 --- p.397 / Chapter C53.1 --- DNA sequence of cDNA subclone XX1#3 using M13 forward -20 primer and the sequence of 3´ة-APl0 D205 --- p.398 / Chapter C53.2 --- Sequence alignment of cDNA subclone XX1#3 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.398 / Chapter C53.3 --- Summary of sequence alignment of cDNA subclone XX1#3 with mouse CYP4A10 --- p.398 / Chapter C54.1 --- DNA sequence of cDNA subclone XX1#9 using Ml3 forward -20 primer and the sequence of 5'-ARP12 --- p.399 / Chapter C54.2 --- Sequence alignment of cDNA subclone XX1#9 with mouse CYP4A10 by BLAST searching with the National Center for Biotechnology Information database --- p.399 / Chapter C54.3 --- Summary of sequence alignment of cDNA subclone XX1#9 with mouse CYP4A10 --- p.399

We have examined the effect of recent onset diabetes on several aspects of hepatic microsomal metabolism in both chemically-induced and spontaneously BB (Bio Breeding) diabetic male and female Wistar rats. Experiments were performed either 4 days post-streptozotocin injection or 4 days after withdrawal of insulin (BB rats). Differential alterations of the diabetic state on hepatic microsomal enzyme activities were observed. Female diabetic rats exhibited no change in benzo[a]pyrene hydroxylase activity, a decrease in testosterone A⁴ hydrogenase, and an increase in aniline hydroxylase. On the other hand, male diabetic rats demonstrated a decrease in hepatic benzo[a]pyrene hydroxylase activity, no change in testosterone A⁴ hydrogenase, and an increase in aniline hydroxylase. Insulin treatment reversed these effects. Benzo[a]pyrene hydroxylase kinetic studies did not reveal marked differences between control and diabetic rats. There were no marked differences between the chemically-induced and genetic models of diabetes with respect to the metabolism studies. Serum testosterone levels were significantly lower than control in BB diabetic males, whereas no change was apparent in female diabetics. Serum insulin determinations suggested that the BB diabetic animals we examined were not severely diabetic although they did exhibit hyperglycemia. Electrophoresis of hepatic microsomal proteins indicated that spontaneous diabetes of short duration altered the protein distribution in the cytochrome R450 region. Two [³H]-estradiol binding sites were detected in rat liver cytosol by Scatchard analysis with a ligand concentration range of 0.05 to 200 nM. The high affinity site, which was specific for estrogens, exhibited a K[sub=d] of ~10⁻¹⁰M and a capacity of ~100 fmol/mg protein in the 50% ammonium sulfate fraction. Unexpectedly, the data suggested that the capacity of this site was greater in males than in females. The moderate affinity binding site exhibited a k[sub=d] of ~10⁻⁷M and a capacity of M0 pmol/mg protein in the whole cytosol fraction. Binding at this site was markedly pH dependent. Both estradiol and dihydrotestosterone competed for binding to this site. A sex difference existed for moderate affinity binding because it was present only in males. We obtained unexpected results in binding studies conducted on a relatively small number of BB diabetic rats. In diabetic males, the capacity of the high affinity site was reduced to 50% of control, whereas the reduction in moderate affinity binding was not nearly so marked. Additional studies using a larger sample size and more sophisticated data analysis are required to verify these results. We concluded that alterations in sex dependent drug metabolism evident in streptozotocin-induced diabetic rats were also seen in the spontaneously diabetic rat model, and were accompanied by changes in the relative disposition of electrophoretically separable microsomal proteins. Changes in circulating androgen levels were also found in BB diabetic males, along with changes in the capacities of certain hepatic steroid binding sites. It is not yet possible to establish mechanistic relationships between these [³H]-estradiol binding sites and modulation of hepatic drug metabolism. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

This study aimed to investigate lipoprotein metabolism in male hamsters fed diets considered to be atherogenic in humans. Livers from adult male hamsters were selected to study aspects of apolipoprotein B metabolism. Isolated hepatocytes in suspension were compared with those maintained under tissue culture conditions. Liver slices were also prepared and compared with isolated suspended hepatocytes. Freshly prepared hepatocytes from the animals were incubated with radiolabelled precursors in suspension, or they were maintained under tissue culture conditions; liver slices were also investigated. The rates of total protein synthesis were of the same order in each of these systems, but protein secretion was impaired in liver slices, probably as a result of diffusion problems associated with the altered architecture of the sliced tissue. Albumin constituted 40 - 50% of the secreted proteins in each system. The rates of VLDL synthesis were increased in cells and slices prepared from animals previously fed sucrose- or fat-rich diets, but the secretion of VLDL was inhibited when diets contained unsaturated fat. The overall synthesis of apolipoprotein B was enhanced by fat-feeding; in the case of suspended hepatocytes, secretion of this protein was decreased when the preceding diet contained fats that were unsaturated; while in the case of liver slices, secretion was paradoxically enhanced. Apolipoprotein B was not degraded at significant rates in hepatocytes prepared from either control or fat-fed hamsters.

No description available.