Methods Enzymol
February 2006
In human, rat, and mice, a UGT1 complex locus provides for developmental-, inducer-, and cell-specific synthesis of a family of chemical-detoxifying isozymes, UDP-glucuronosyltransferases, which prevent toxicities, mutagenesis, and/or carcinogenesis. Between 10 and 14 first exons with individual promoter elements are tandemly arrayed upstream of 4 shared exons so as to synthesize independently as many overlapping primary transcripts. RNA splice sites allow a lead exon to join the common exons to generate mRNAs with unique 5' ends, but common 3' ends.
View Article and Find Full Text PDFPiscivorous wildlife, such as mink (Mustela vison), routinely are exposed to mercury (Hg) in their natural environment at levels that may cause adverse behavioral outcomes. The purpose of this study was to determine if a correlation exists between neurochemical receptors and concentrations of Hg in the brains of wild mink. Specifically, receptor-binding assays were conducted to characterize the muscarinic cholinergic (mACh) and dopaminergic-2 (D2) systems in brain tissues collected from mink trapped in the Yukon Territory, Ontario, and Nova Scotia (Canada), and values were correlated with total Hg and methyl Hg (MeHg) concentrations in the brains.
View Article and Find Full Text PDFAnalytical solutions, describing the time-dependent DNAPL source-zone mass and contaminant discharge rate, derived previously in Part I [Falta, R.W., Rao, P.
View Article and Find Full Text PDFAnalytical solutions are developed for approximating the time-dependent contaminant discharge from DNAPL source zones undergoing dissolution and other decay processes. The source functions assume a power relationship between source mass and chemical discharge and can consider partial DNAPL source remediation (depletion) at any time after the initial DNAPL release. The source functions are used as a time-dependent boundary condition in an idealized chemical transport model to develop leading order approximations of the plume response to DNAPL source removal.
View Article and Find Full Text PDFJ Toxicol Environ Health A
August 2005
Disruption of neurochemical parameters in blood and brain tissues can be used as early biomarkers of neurotoxicity in human and wildlife epidemiological studies. To investigate the feasibility of biomarker measurements in field samples obtained from remote locations, tissue storage limits were determined with human blood and mink cortex tissue using efficient and cost-effective microplate assays. Results show that isolated blood platelets and plasma can be stored at 4 degrees C for 4 wk before measurement of monoamine oxidase (MAO) and cholinesterase (ChE) activities, while human lymphocytes can be stored at 4 degrees C for up to 2 d before muscarinic acetylcholine (mACh) receptor binding analysis.
View Article and Find Full Text PDFFish-eating wildlife, such as river otters (Lontra canadensis), accumulate mercury (Hg) at concentrations known to impair animal behavior, but few studies have explored the underlying biochemical changes that precede clinical neurotoxicity. The objective of this study was to determine if Hg exposure can be related to concentrations of neurochemical receptors in river otters. River otter carcasses (n = 66) were collected in Ontario and Nova Scotia (Canada) by local trappers in 2002-2004.
View Article and Find Full Text PDFMercury (Hg) is a ubiquitous pollutant that can disrupt neurochemical signaling pathways in mammals. It is well documented that inorganic Hg (HgCl(2)) and methyl Hg (MeHg) can inhibit the binding of radioligands to the muscarinic acetylcholine (mACh) receptor in rat brains. However, little is known concerning this relationship in specific anatomical regions of the brain or in other species, including humans.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2005
UDP-glucuronosyltransferase (UGT) isozymes catalyze detoxification of numerous chemical toxins present in our daily diet and environment by conjugation to glucuronic acid. The special properties and enzymatic mechanism(s) that enable endoplasmic reticulum-bound UGT isozymes to convert innumerable structurally diverse lipophiles to excretable glucuronides are unknown. Inhibition of cellular UGT1A7 and UGT1A10 activities and of [33P]orthophosphate incorporation into immunoprecipitable proteins after exposure to curcumin or calphostin-C indicated that the isozymes are phosphorylated.
View Article and Find Full Text PDFThe pleomorphic adenoma is the most common benign tumour of the major and minor salivary glands. We report a 40-year-old female patient, who presented with progressive swelling and deformity of the left side of her nose for last 2 years. On a lateral rhinotomy a mass (4 cm X3 cm in size) was found to be arising from the cartilaginous part of the nasal septum.
View Article and Find Full Text PDFAlthough the promising immunosuppressant, mycophenolic acid (MPA), has many desirable properties and is widely prescribed for organ transplant recipients, its high oral dosage requirement is not understood. Whereas previous Northern blot analysis by Basu and colleagues (2004) located the mRNAs encoding MPA primary metabolizers, UDP-glucuronosyltransferases (UGTs) 1A7, 1A8, 1A9, and 1A10, in human gastrointestinal (GI) tissues, in situ hybridization analysis of mRNAs found that the isozymes were restricted to the mucosal layer of various GI organs. Concomitantly, MPA was glucuronidated by microsomes isolated from normal adjoining specimens.
View Article and Find Full Text PDFAmong gastrointestinal distributed isozymes encoded at the UGT1 locus, UDP-glucuronosyltransferase 1A10 (UGT1A10) metabolizes a number of important chemicals. Similar to broad conversion of phytoestrogens (Basu, N. K.
View Article and Find Full Text PDFUDP-glucuronosyltransferase (UGT) isozymes detoxify metabolites, drugs, toxins, and environmental chemicals via conjugation to glucuronic acid. Based on the extended UGT1 locus combined with Northern blot analysis and in situ hybridization, we determined the distribution of UGT1A1 and UGT1A7 through UGT1A10 mRNAs and found them for the first time segmentally distributed in the mucosal epithelia layer of the gastrointestinal tract. Biochemically, recombinant isozymes exhibited pH optima of 5.
View Article and Find Full Text PDFBiochem Biophys Res Commun
March 2003
Our discovery of rapid down-regulation of human bilirubin UDP-glucuronosyltransferase (UGT) in colon cell lines that was transient and irreversible following curcumin- and calphostin-C-treatment, respectively, suggested phosphorylation event(s) were involved in activity. Likewise, bilirubin-UGT1A1 expressed in COS-1 cells was inhibited by curcumin and calphostin-C. Because calphostin-C is a highly specific protein kinase C (PKC) inhibitor, we examined and found 4 to 5 predicted PKC phosphorylation sites in 11 UGTs examined.
View Article and Find Full Text PDFComp Biochem Physiol A Mol Integr Physiol
March 2003
The purpose of this study was to characterize the association between hepatic heat shock protein 70 (hsp70) and the glucocorticoid receptor in rainbow trout that were exposed to heat stress, cortisol, and beta-naphthoflavone. This study is the first to document that the glucocorticoid receptor complex in rainbow trout hepatic tissues contains hsp70. Heat stress significantly increased levels of total cellular hsp70, and by discerning the association of hsp70 with the glucocorticoid receptor, we demonstrated that heat stress significantly increased the amount of hsp70 not bound to the glucocorticoid receptor, while significantly decreasing the amount of hsp70 bound to the glucocorticoid receptor.
View Article and Find Full Text PDFMany clinical trials have shown that the most important prognostic variable in patients with malignant glioma is advanced age. However, can some patients aged >60 years still have relatively good outcomes with conventional surgical and radiotherapeutic treatment? A previous audit of practice (1983-89) suggested that functional status was an important prognostic variable in the elderly. We have reviewed a further cohort (1989-96) to evaluate changes in practice and outcomes given advances in neuroimaging, neurosurgery and radiotherapy.
View Article and Find Full Text PDFObjective: To determine urinary citrate excretion in children with nephrolithiasis and normal controls.
Design: Prospective.
Setting: Tertiary care center in New Delhi.
Despite decades of intensive investigation, important questions remain regarding the functional, ecological, and evolutionary roles of heat shock proteins. In this paper, we discuss the utility of fish as a model system to address these questions, and review the relevant studies of heat shock protein genes and the regulation of their expression in fish. Although molecular studies of the heat shock proteins in fish are still in their early descriptive phase, data are rapidly being collected.
View Article and Find Full Text PDFGen Comp Endocrinol
October 2001
We studied the relationship between heat stress (2 h, +12 degrees ) and increased levels of circulating cortisol (50 microg cortisol/g body weight) on heat shock protein 70 (hsp70) levels in liver and gill tissues of rainbow trout (Oncorhynchus mykiss) and tilapia (Oreochromis mossambicus). The administration of cortisol by intraperitoneal injection (no heat stress) did not alter tissue hsp70 levels compared to sham implanted (no heat stress) trout and tilapia. We found elevated levels of cortisol significantly suppressed the heat stress-induced levels of hepatic hsp70 by 34.
View Article and Find Full Text PDFFifty six years lady presented with pure cerebellar ataxia with positive family history from paternal side presented to our clinic. DNA screening found to be SCA6. This is the first case report of SCA6 from India.
View Article and Find Full Text PDFThe original novel UGT1 complex locus previously shown to encode six different UDP-glucuronosyltransferase (transferase) genes has been extended and demonstrated to specify a total of 13 isoforms. The genes are designated UGT1A1 through UGT1A13p with four pseudo ones. UGT1A2p and UGT1A11p through UGT1A13p have either nucleotide deletions or flawed TATA boxes and are therefore pseudo.
View Article and Find Full Text PDFThis study investigated whether ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) could be predicted from induction equivalency factors (IEF). The test PAHs were classified into strong and weak inducers on the basis of similar exposure-response curves. Induction equivalency factors of strong inducers, based on benzo[k]fluoranthene (BkF) as the reference compound, ranged from 0.
View Article and Find Full Text PDFAlthough glucuronidation is considered a necessary step in aromatic amine-induced bladder cancer, the specific enzymes involved are not known. This study assessed the capacity of five different human recombinant UDP-glucuronosyltransferases expressed in COS-1 cells to glucuronidate benzidine, its metabolites and 4-aminobiphenyl. [(14)C]UDP-glucuronic acid was used as co-substrate.
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