Searching for Tissue-Specific Expression Pattern-Linked Nucleotides of UGT1A Isoforms

UDP-glucuronosyltransferases 1A isoforms belong to a superfamily of microsomal enzymes responsible for glucuronidation of numerous endogenous and exogenous compounds. The nine functional UGT1A isoforms are encoded by a single UGT1A gene locus with multiple first exons. The expression of the UGT1A transcripts was measured by quantitative RT-PCR in 23 normal human tissues. The tissue-specific expression patterns were observed in 13 tissues. To understand the regulation mechanism that is responsible for the tissue-specific expression patterns, we scanned the DNA sequence alignments of the putative promoter regions, exon 1 sequences and intron 1 sequences for those expression-pattern-linked nucleotides. Using one of the expression-pattern-linked nucleotides for livers as an example, we showed that a database comprised of these expression-pattern-linked nucleotides could be used to generate focused hypotheses on the problem of tissue-specific expression, which is critical for tissue-specific pharmacodynamics of anticancer drugs

Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview

The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemical mediators and their link to breast cancer development and progression, whereas, in opposition, 2-methoxylated estrogens appear to be protective. Recent data also indicate that breast tissue possesses enzymatic machinery to inactivate and eliminate E(2 )and its oxidized and methoxylated metabolites through conjugation catalyzed by UDP-glucuronosyltransferases (UGTs), which involves the covalent addition of glucuronic acid. In opposition to other metabolic pathways of estrogen, the UGT-mediated process leads to the formation of glucuronides that are devoid of biologic activity and are readily excreted from the tissue into the circulation. This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E(2 )and its metabolites, and evidence regarding their potential role in breast cancer

Power budget study for passive target detection and imaging using secondary applications of GPS signals in bistatic radar systems

Signals from satellite systems like GPS, IRIDUM and Globalstar that are reflected from moving or stationary objects are utilised for their detection in a synthetic aperture bistatic radar system (SAR). The movements of the satellite and its position at different coordinates with respect to time can serve as a base for a synthetic aperture. This paper focuses on the development of a system based on the analysis of indirect signals, in particular GPS signals. The main concern in this study is the low power of the GPS signal at the earth's surface (typically about -160 dB). Due to the nature of the reflector/target, some power will be absorbed, and hence result in a further reduction in signal strength reflected by the target. However, the other equally important concern here is the ground and sea clutter, which is 18-22 dB stronger than the direct signal level. Here we present theoretical results of both the maximum detection range and land clutter contributions of the air target detection by bistatic SAR that utilizes the existing GPS satellite as the transmitting signal source

Three-dimensional bistatic synthetic aperture radar imaging system: Spatial resolution analysis

A mathematical framework for analysing the spatial resolving capability of a general three-dimensional bistatic synthetic aperture radar imaging system, in which the transmitter, receiver and imaged object (or region of interest) may be non-coplanar and in which the transmitter and/or receiver may be moving, is presented. With Earth observation applications in mind, this framework is used to characterise quantitatively the two-dimensional ground-plane resolving capability of the three-dimensional imaging system. The theoretical results are confirmed via simulations

CDNA Expression Studies of Rat Liver Aryl Sulfotransferase

A cDNA encoding an isoenzyme of rat liver aryl sulphotransferase was isolated from a rat liver bacteriophage Lambda gt 11 library by the polymerase chain reaction technique. The resulting cDNA was functionally expressed in COS-7 cells and characterised by determining the sulphating capacity of the cells with a range of substrates. The COS-expressed enzyme catalysed the sulphation of both phenol and dopamine with Kms of the same order as those obtained for the high affinity isozyme in rat liver cytosol, while low activity was observed with tyrosine methyl ester. The common food additive vanillin was also a good substrate for sulphate conjugation. The sulphation of vanillin catalysed by the COS-expressed enzyme was consistent with a single enzyme system, in contrast, the kinetics of the reaction catalysed by cytosolic sulphotransferase indicated that vanillin was sulphated by more than one isozyme