http://espace.library.uq.edu.au/ The University of Queensland en Fez http://blogs.law.harvard.edu/tech/rss http://espace.library.uq.edu.au/view/UQ:130530 Study objective: We determine whether single-dose activated charcoal (SDAC) administration after citalopram overdose reduces the proportion of patients developing abnormal QT prolongation. Methods: Data were collected retrospectively for citalopram overdose patients presenting to 8 emergency departments. Demographics, dose, coingested drugs, SDAC administration, and serial ECGs were extracted from medical records. The primary outcome was the proportion of patients who had an observed QT,RR combination at any time above an abnormal threshold, established as a predictor of torsade de pointes. We compared the proportion of patients with QT prolongation who received or did not receive SDAC. These data were analyzed within a Bayesian framework, using probabilities of abnormal QT,RR combinations with and without derived from a previous single-center study. WinBUGS was used to generate posterior estimates and credible intervals of the relative risk by combining the prior probabilities and the study data. Results: SDAC was administered on average 2.1 hours (range, 0.5 to 6.25 hours) after ingestion in 48 of 254 admissions, and abnormal QT,RR combinations occurred in 2 cases (4.2%), compared with 23 of 206 (11.2%) cases not receiving SDAC. There did not appear to be any clinically important difference in age, sex, dose, and cardiotoxic coingestants, between the 2 groups. No cases of torsade de pointes occurred. The estimated relative risk of having an abnormal QT,RR combination for SDAC compared to no SDAC was 0.28 (0.06 to 0.70) (median with 2.5% and 97.5% credible limits). The probability that the relative risk was less than 1.0 was 0.99, which can be interpreted as very strong evidence in favor of a beneficial effect of SDAC. The absolute risk difference was estimated as 7.5% and the median number needed to treat as 13.3. Conclusion: SDAC may be effective in reducing the risk of a prolonged QT in patients after citalopram overdose. Current trends toward nonuse of activated charcoal should be evaluated to determine whether patients poisoned by specific agents may benefit from activated charcoal administration. 2008-02-18T00:00:00Z Isbister, G. K. og Friberg, L. E. og Stokes, B. og Buckley, N. A. og Lee, C. og Gunja, N. og Brown, S. G. og MacDonald, E. og Graudins, A. og Hoidgate, A. og Duffull, S. B. http://espace.library.uq.edu.au/view/UQ:59405 Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a member of the steroid hormone receptor superfamily. In rodents, PPAR alpha. alters genes involved in cell cycle regulation in hepatocytes. Some of these genes are implicated in neuronal cell death. Therefore, in this study, we examined the toxicological consequence of PPAR alpha activation in rat primary cultures of cerebellar granule neurons. Our studies demonstrated the presence of PPAR alpha mRNA in cultures by reverse transcriptase-polymerase chain reaction. After 10 days in vitro, cerebellar granule neuron cultures were incubated with the selective PPAR alpha activator 4-chloro-6-(2,3-xylidino)2-pyrimidinylthioacetic acid (Wy-14,643). The inherent toxicity of Wy-14,643 and the effect of PPAR alpha activation following toxic stimuli were assessed. In these studies, neurotoxicity was induced through reduction of extracellular [KCl] from 25 mM to 5.36 mM. We observed no inherent toxicity of Wy-1 4,643 (24 hr) in cultured cerebellar granule cells. However, after reduction of [KCl], cerebellar granule cell cultures incubated with Wy-14,643 showed significantly greater toxicity than controls. These results suggest a posssible role for PPAR(x in augmentation of cerebellar granule neuronal death after toxic stimuli. (C) 2001 Wiley-Liss, Inc. 2007-08-14T00:00:00Z Smith, SA og May, FJ og Monteith, GR og Roberts-Thomson, SJ http://espace.library.uq.edu.au/view/UQ:95675 2007-08-23T00:00:00Z Smith, S. A. og May, F. J. og Monteith, G. R. og Roberts-Thomson, S. J. http://espace.library.uq.edu.au/view/UQ:99493 2007-08-24T00:00:00Z Fiore, S.A. og La Caze, A. og Cutts, C. og D'Amore, R. og Souzani, S. og Behan, K. http://espace.library.uq.edu.au/view/UQ:82729 2007-08-15T00:00:00Z McGuire, T http://espace.library.uq.edu.au/view/UQ:121166 The Dde-derived carboxy protecting group, 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl ester (ODmab) has been developed into a carboxy functional linker. The stability of the linker to standard acid and base conditions employed in Fmoc/tBu SPPS has been demonstrated and its utility illustrated by the construction of model peptides, Leu-enkephalin and Human Angiotensin II. 2007-12-20T00:00:00Z Chhabra, S. R. og Parekh, H. og Khan, A. og Bycroft, B. og Kellam, B. http://espace.library.uq.edu.au/view/UQ:152706 2008-08-12T00:00:00Z South, S. M. og Dao, C. B. og Wyse, B. og Smith, M. T. http://espace.library.uq.edu.au/view/UQ:184953 2009-10-15T00:00:00Z Shi, A. L. og Firth, S. I. http://espace.library.uq.edu.au/view/UQ:123217 A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X). 2008-01-25T00:00:00Z Marinaki, AM og Champion, M og Kurian, MA og Simmonds, HA og Marie, S og Vincent, MF og van den Berghe, G og Duley, JA og Fairbanks, LD http://espace.library.uq.edu.au/view/UQ:225658 2010-12-20T00:00:00Z Chen, Bee Chin og McGowan, Ivan og Thong, Meow Keong og Pitt, James og Yunus, Zabedah M og Khoo, Teck Beng og Ngu, Lock Hock og Duley, John A. http://espace.library.uq.edu.au/view/UQ:163500 2009-02-10T00:00:00Z Kairuz, T. E. og Harrison, J. og Lay-Lee, R. og Crengle, S. og Davis, P. B. http://espace.library.uq.edu.au/view/UQ:274603 2012-05-23T14:54:09Z La Caze, Adam og Gujral, Gina og Cottrell, Neil http://espace.library.uq.edu.au/view/UQ:164692 2009-02-17T00:00:00Z Kairuz, T. og Naidoo, P. http://espace.library.uq.edu.au/view/UQ:103946 2007-08-23T00:00:00Z Hennig, S og Wainwright, C E og Bell, S og Miller, H og Charles, B G og Duffull, S B http://espace.library.uq.edu.au/view/UQ:103949 Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data. 2007-08-23T00:00:00Z Hennig, S. og Wainwright, C. E. og Bell, S. og Miller, H. og Charles, B. G. og Duffull, S. B. http://espace.library.uq.edu.au/view/UQ:130999 Aim The primary objective of the study was to estimate the population pharmacokinetic parameters for itraconazole and hydroxy-itraconazole, in particular, the relative oral bioavailability of the capsule compared with solution in adult cystic fibrosis patients, in order to develop new dosing guidelines. A secondary objective was to evaluate the performance of a population optimal design. Methods The blood sampling times for the population study were optimized previously using POPT v.2.0. The design was based on the administration of solution and capsules to 30 patients in a cross-over study. Prior information suggested that itraconazole is generally well described by a two-compartment disposition model with either linear or saturable elimination. The pharmacokinetics of itraconazole and the metabolite were modelled simultaneously using NONMEM. Dosing schedules were simulated to assess their ability to achieve a trough target concentration of 0.5 mg ml(-1). Results Out of 241 blood samples, 94% were taken within the defined optimal sampling windows. A two-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order metabolism to the hydroxy-metabolite. For itraconazole the absorption rate constants (between-subject variability) for capsule and solution were 0.0315 h(-1) (91.9%) and 0.125 h(-1) (106.3%), respectively, and the relative bioavailability of the capsule was 0.82 (62.3%) (confidence interval 0.36, 1.97), compared with the solution. There was no evidence of nonlinearity. Simulations from the final model showed that a dosing schedule of 500 mg twice daily for both formulations provided the highest chance of target success. Conclusion The optimal design performed well and the pharmacokinetics of itraconazole and hydroxy-itraconazole were described adequately by the model. The relative bioavailability for itraconazole capsules was 82% compared with the solution. 2008-02-19T00:00:00Z Hennig, Stefanie og Waterhouse, Timothy H. og Bell, Scott C. og France, Megan og Wainwright, Claire E. og Miller, Hugh og Charles, Bruce G. og Duffull, Stephen B. http://espace.library.uq.edu.au/view/UQ:164478 2009-02-16T00:00:00Z Zolezzi, M. og Forbes, A. og Kairuz, T. http://espace.library.uq.edu.au/view/UQ:292723 2013-03-04T10:55:29Z Stacey, Sonya og Whitfield, Karen http://espace.library.uq.edu.au/view/UQ:290152 Traditional Chinese medicines (TCMs) are in widespread use around the world, increasingly so in western nations as the complementary therapy of choice. Nonetheless, quality and safety of TCMs remain key concerns, hindering their wider popularity among the international healthcare fraternity. Cutting-edge analytical technologies are urgently required to address these concerns, ensuring reproducible identification and verification of constituents within any given TCM. Recent improvements in engineering advanced analytical instrumentation with improved sensitivity and precision to allow greater resolution of multi-component mixtures are driving the quality-control standards of TCMs towards universally-acceptable standards. We review recent applications of key analytical techniques in quality assurance and authentication of herbs and their extracts. We highlight the emerging role of chemical fingerprinting of TCMs and the latest regulatory requirements imposed on Chinese herbal medicines utilizing chromatographic fingerprinting. 2013-01-28T16:42:53Z Jing, Jing og Ren, Weichao og Chen, Si Bao og Wei, Ming og Parekh, Harendra S. http://espace.library.uq.edu.au/view/UQ:278303 Cervical cancer is the second leading cause of cancer in women worldwide. Human papillomavirus (HPV) is responsible for all cases of cervical cancer. Commercial prophylactic HPV vaccines are now available, but unfortunately these vaccines have no therapeutic effect against established HPV infections. In order to accelerate the control of cervical cancer and treat established HPV infections, it is necessary to develop therapeutic vaccines to eradicate HPV by generating cell-mediated immunity against HPV infected cells. Two HPV-encoded early proteins, the E6 and E7 oncoproteins, are the preferred targets because they are consistently expressed in virtually all cervical cancer cells and are necessary for the induction and maintenance of HPV-associated disease. A variety of vaccine strategies have been employed targeting immune responses to these proteins. Peptide-based vaccines are a promising strategy for the development of therapeutic HPV vaccines because of their safety, stability, and ease of production. This review summarizes the prospects of peptidebased vaccines for the treatment of established HPV infections. We address the challenges that scientists currently face for developing peptide-based vaccines and explore feasible strategies for improving the potency of the induced immune response with the aim of treating established HPV infections. 2012-07-30T09:40:09Z Liu, Tzu-Yu og Hussein, Waleed M. og Toth, Istvan og Skwarczynski, Mariusz http://espace.library.uq.edu.au/view/UQ:292722 2013-03-04T10:53:07Z Stacey, Sonya og Whitfield, Karen og Wainwright, Claire http://espace.library.uq.edu.au/view/UQ:122991 Adverse drug reactions to azathioprine (AZA), the pro-drug of 6-mercaptopurine (6-MP), occur in 15% to 28% of patients and the majority are not explained by thiopurine methyltransferase (TPMT) deficiency. Inosine triphosphate pyrophosphatase (ITPase) deficiency results in the benign accumulation of the inosine nucleotide ITP. 6-MP is activated through a 6-thio-IMP intermediate and, in ITPase deficient patients, potentially toxic 6-thio-ITP is predicted to accumulate. The association between polymorphism in the ITPA gene and adverse drug reactions to AZA therapy was studied in patients treated for inflammatory bowel disease. Sixty-two patients with inflammatory bowel disease suffering adverse drug reactions to AZA therapy were genotyped for ITPA 94C>A and IVS2 + 21A>C polymorphisms, and TPMT*3A, *3C, *2 polymorphisms. Genotype frequencies were compared to a consecutive series of 68 controls treated with AZA for a minimum of 3 months without adverse effect. The ITPA 94C>A deficiency-associated allele was significantly associated with adverse drug reactions [odds ratio (OR) 4.2, 95% confidence interval (CI) 1.6-11.5, P = 0.0034]. Significant associations were found for flu-like symptoms (OR 4.7, 95% CI 1.2-18.1, P = 0.0308), rash (OR 10.3, 95% CI 4.7-62.9, P = 0.0213) and pancreatitis (OR 6.2, CI 1.1-32.6, P = 0.0485). Overall, heterozygous TPMT genotypes did not predict adverse drug reactions but were significantly associated with a subgroup of patients experiencing nausea and vomiting as the predominant adverse reaction to AZA therapy (OR 5.5, 95% CI 1.4-21.3, P = 0.0206). Polymorphism in the ITPA gene predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency. (C) 2004 Lippincott Williams Wilkins. 2008-01-25T00:00:00Z Marinaki, AM og Ansari, A og Duley, JA og Arenas, M og Sumi, S og Lewis, CM og Shobowale-Bakre, EM og Escuredo, E og Fairbanks, LD og Sanderson, JD http://espace.library.uq.edu.au/view/UQ:163125 2009-02-05T00:00:00Z Hewavitharana, A. K. og Christensen, E. og Golding, G. og Scheelings, P. http://espace.library.uq.edu.au/view/UQ:99213 2007-08-24T00:00:00Z Moore, B. og Azzopardi, J. og Cabot, P. J. og Gray, P. og Roufogalis, B. og Smith, M. T. http://espace.library.uq.edu.au/view/UQ:116710 A gas chromatography-mass spectrometry assay method for the analysis of lauric, myristic, and palmitic acids and their omega and omega-1 hydroxylated metabolites from in vitro incubations of cytochrome P450 CYP4A1, involving solid-phase extraction and trimethysityl derivatization, was developed. The assay was linear, precise, and accurate over the range 0.5 to 50 muM for all the analytes. It has the advantages of a more rapid analysis time, an improved sensitivity, and a wider range of analytes compared with other methods. An artificial membrane system was optimized for application to purified CYP4A1 enzyme by investigating the molar ratios of cytochrome b(5) and cytochrome P450 reductase present in the incubation mixture. Using this method, the kinetics of omega and omega(-1) oxidation of lauric, myristic, and palmitic acids by CYP4A enzymes were measured and compared in rat liver microsomes and an artificial membrane system. (C) 2003 Elsevier Inc. All rights reserved. 2007-10-17T00:00:00Z Holmes, Victoria E. og Bruce, Mary og Shaw, P. Nicholas og Bell, David R. og Qi, Fan Ming og Barrett, David A. http://espace.library.uq.edu.au/view/UQ:148760 2008-06-06T00:00:00Z McGuire, T. og Jackson, C. og Dommers, E. og Nyst, P. http://espace.library.uq.edu.au/view/UQ:148788 2008-06-06T00:00:00Z http://espace.library.uq.edu.au/view/UQ:121167 Three standardised, capillary zone electrophoresis-electrospray ionisation mass spectrometry (CZE-ESI-MS) methods were developed for the analysis of six drug candidates and their respective process-related impurities comprising a total of 22 analytes with a range of functional groups and lipophilicities. The selected backround electrolyte conditions were found to be: 60/40 v/v 10 mM ammonium formate pH 3.5/organic, 60/40 v/v 10 mM ammonium acetate pH 7.0/organic and 10 mM piperidine, pH 10.5, where the organic solvent is 50/50 v/v methanol/acetonitrile. The coaxial sheath flow consisted of either 0.1% v/v formic acid in 50/50 v/v methanol/water, or 10 mM ammonium acetate in 50/50 v/v methanol/water, depending on the mixture being analysed. Factor analysis and informational theory were used to quantify the orthogonality of the methods and predict their complementarities. The three selected CZE-ESI-MS methods allowed the identification of 21 out of 22 of all the drug candidates and their process-related impurities and provided orthogonality with four established high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. These methodologies therefore form the basis of a generic approach to impurity profiling of pharmaceutical drug candidates and can be applied with little or no analytical method development, thereby offering significant resource and time savings. 2007-12-20T00:00:00Z Vassort, Aurélie og Barrett, David A. og Shaw, P. Nicholas og Ferguson, Paul D. og Szucs, Roman http://espace.library.uq.edu.au/view/UQ:67158 2007-08-15T00:00:00Z Robinson, M. T. http://espace.library.uq.edu.au/view/UQ:62959 2007-08-14T00:00:00Z McGuire, T. http://espace.library.uq.edu.au/view/UQ:271556 2012-03-26T12:04:09Z Barraclough, Katherine A. og Isbel, Nicole M. og Johnson, David W. og Hawley, Carmel M. og Lee, Katie J. og Mcwhinney, Brett C. og Ungerer, Jacobus P. og Campbell, Scott B. og Leary, Diana R. og Staatz, Christine E. http://espace.library.uq.edu.au/view/UQ:63234 A lipoamino acid based synthetic peptide, (Lipid Core Peptide, LCP) derived from the conserved region of group A streptococci (GAS) was evaluated as potential candidate in a vaccine to prevent GAS-associated diseases, including rheumatic heart disease and post-streptococcal acute glomerulonephritis. Multiple copies of a peptide sequence from the bacterial surface M protein were incorporated into a lipid core and it was used to immunize mice with and without the application of adjuvant. The LCP construct had significantly enhanced immunogenicity compared with the monomeric peptide epitope. Furthermore, the peptides incorporated into the LCP system generated antibodies without the use of any conventional adjuvant. 2007-08-14T00:00:00Z Horvath, Aniko og Olive, Colleen og Wong, Allan og Clair, Timothy og Yarwood, Penny og Good, Michael og Toth, Istvan http://espace.library.uq.edu.au/view/UQ:123221 The enzyme inosine triphosphate pyrophosphatase (ITPase) catalyses the pyrophosphohydrolysis of ITP to IMP. ITPase deficiency is a clinically benign autosomal recessive condition characterised by the abnormal accumulation of ITP in erythrocytes. A deficiency of ITPase may predict adverse reactions to therapy with the thiopurine drug 6-mercaptopurine and its prodrug azathioprine. In this study, we examine the frequencies of ITPA polymorphisms in 100 healthy Japanese individuals. The allele frequency of the 94C > A variant in the Japanese sample was 0.135 (Caucasian allele frequency 0.06). The IV2 + 21A > C polymorphism was not found in Japanese (Caucasian allele frequency 0.130). Allele frequencies of the 138G > A, 561G > A and 708G > A polymorphisms were 0.57, 0.18 and 0.06 respectively in the Japanese population, and with the exception of the 138G > A polymorphism, similar to allele frequencies in Caucasians. 2008-01-25T00:00:00Z Marinaki, AM og Sumi, S og Arenas, M og Fairbanks, L og Harihara, S og Shimizu, K og Ueta, A og Duley, JA http://espace.library.uq.edu.au/view/UQ:195886 2010-02-19T00:00:00Z Dean, A. http://espace.library.uq.edu.au/view/UQ:41960 The effect of hydration (priming) treatment on dormancy release in annual ryegrass seeds from two populations was investigated. Hydration duration, number, and timing with respect to after-ripening were compared in an experiment involving 15 treatment regimens for 12 wk. Seeds were hydrated at 100% relative humidity for 0, 2, or 10 d at Weeks 1, 6, or 12 of after-ripening. Dormancy status was assessed after each hydration treatment by measuring seed germination at 12-hourly alternating 25/15 C (light/dark) periods using seeds directly from the hydration treatment and seeds subjected to 4 d postpriming desiccation. Seeds exposed to one or more hydration events during the 12 wk were less dormant than seeds that remained dry throughout after-ripening. The longer hydration of 10 d promoted greater dormancy loss than either a 2-d hydration or no hydration. For the seed lot that was most dormant at the start of the experiment, two or three rather than one hydration event or a hydration event earlier rather than later during after-ripening promoted greater dormancy release. These effects were not significant for the less-dormant seed lot. For both seed lots, the effect of a single hydration for 2 d at Week 1 or 6 of after-ripening was not manifested until the test at Week 12 of the experiment, suggesting that the hydration events alter the rate of dormancy release during subsequent after-ripening. A hydrothermal priming time model, usually used for modeling the effect of priming on germination rate of nondormant seeds, was successfully applied to dormancy release resulting from the hydration treatments. 2007-08-13T00:00:00Z Gallagher, Robert S. og Steadman, Kathryn J. og Crawford, Andrew D. http://espace.library.uq.edu.au/view/UQ:163325 2009-02-06T00:00:00Z Boyce, Rosalie og Borthwick, Alan http://espace.library.uq.edu.au/view/UQ:231386 2011-03-07T00:00:00Z Nissen, Lisa M. http://espace.library.uq.edu.au/view/UQ:154931 Recent research has led to a purinergic hypothesis of schizophrenia. It is postulated that increased adenosinergic transmission reduces the affinity of dopamine agonists for dopamine receptors. Allopurinol may increase circulating pools of adenosine and as such may ultimately have antipsychotic and anxiolytic effects. (non- author abstract) 2008-09-01T00:00:00Z Nissen, Lisa http://espace.library.uq.edu.au/view/UQ:97842 2007-08-24T00:00:00Z Cutts, C. og La Caze, A. og Rees, K. og Behan, K. og Punchard, H. og Lum, E. P. M. og Lees, J. og Hutchinson, J. og Tett, S. E. http://espace.library.uq.edu.au/view/UQ:83284 2007-08-15T00:00:00Z Hunter, A. http://espace.library.uq.edu.au/view/UQ:225665 A substantial minority of children are born as a consequence of an unplanned pregnancy. Yet little is known about the impact of unplanned/unwanted pregnancy (UP) on long-term health outcomes for children. This study aimed to examine the association between UP and child mental health and behavioural problems at 14 years, and whether this association is confounded or mediated by other variables. Data were from a pre-birth prospective study that included 4765 mothers and their children (48.4% female and 51.6% male) followed up from pregnancy to 14 years of the child's age in Brisbane, Australia. Child anxiety/depression, aggression, delinquency, attention problems, withdrawal problems, somatic complaints, social problems, thought problems, internalizing, externalizing and total problems were measured using the Achenbach's Youth Self Report at 14 years. Child smoking and alcohol consumption were self-reported at 14 years. UP was prospectively assessed at the first antenatal visit of pregnancy. UP as reported by mothers at first antenatal visit predicted elevated levels of problem behaviours and increased substance use in children at 14 years. The impact of UP on child mental health and problem behaviours is partly due to the confounding effect of other variables, such as maternal socio-demographic status, mental health and substance use during pregnancy. Further research is needed to investigate the mechanism of association between UP and child aggression and early alcohol consumption at 14 years. © 2010 Elsevier Ltd. 2010-12-20T00:00:00Z Hayatbakhsh, Mohammad Reza og Najman, Jackob M. og Khatun, Mohsina og Mamun, Abdullah A. og Bor, William og Clavarino, Alexandra M. http://espace.library.uq.edu.au/view/UQ:237192 2011-03-17T00:00:00Z Prakash, Krishneeta og Nissen, Lisa M. og Kyle, Greg og Smith, Simon http://espace.library.uq.edu.au/view/UQ:226274 2011-01-05T00:00:00Z Chowdhury, M. Ashraf og Roberts-Thomson, Sarah J. og Monteith, Gregory R. http://espace.library.uq.edu.au/view/UQ:61965 Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population. 2007-08-14T00:00:00Z Eisen, D. P. og Saul, A. og Fryauff, D. J. og Reeder, J. C. og Coppel, R. L. http://espace.library.uq.edu.au/view/UQ:273025 Caveolin-1 is an essential structural protein of caveolae, specialized plasma membrane organelles highly abundant in endothelial cells, where they regulate multiple functions including angiogenesis. Caveolin-1 exerts a tonic inhibition of endothelial nitric oxide synthase (eNOS) activity. Accordingly, caveolin-1 genedisrupted mice have enhanced eNOS activity as well as increased systemic nitric oxide (NO) levels. We hypothesized that excess eNOS activity, secondary to caveolin deficiency, would mediate the decreased angiogenesis observed in caveolin-1 genedisrupted mice. We tested tumor angiogenesis in mice lacking either one or both proteins, using in vitro, ex vivo, and in vivo assays. We show that endothelial cell migration, tube formation, cell sprouting from aortic rings, tumor growth, and angiogenesis are all significantly impaired in both caveolin-1null and eNOS-null mice. We further show that these parameters were either partially or fully restored in double knockout mice that lack both caveolin-1 and eNOS. Furthermore, the effects of genetic ablation of eNOS are mimicked by the administration of the NOS inhibitor N-nitro-l-arginine methyl ester hydrochloride (L-NAME), including the reversal of the caveolin-1null mouse angiogenic phenotype. This study is the first to demonstrate the detrimental effects of unregulated eNOS activity on angiogenesis, and shows that impaired tumor angiogenesis in caveolin-1null mice is, at least in part, the result of enhanced eNOS activity. 2012-04-23T15:06:50Z Morais, Christudas og Ebrahem, Quteba og Anand-Apte, Bela og Parat, Marie-Odile http://espace.library.uq.edu.au/view/UQ:289307 2013-01-18T10:45:56Z Shekar, Kiran og Roberts, Jason A. og Ghassabian, Sussan og Mullany, Daniel V. og Wallis, Steven C. og Smith, Maree T. og Fraser, John F. http://espace.library.uq.edu.au/view/UQ:175538 Caveolin-1 is a palmitoylated protein involved in the formation of plasma membrane subdomains termed caveolae, intracellular cholesterol transport, and assembly and regulation of signaling molecules in caveolae. Caveolin-1 interacts via a consensus binding motif with several signaling proteins, including H-Ras. Ras oncogene products function as molecular switches in several signal transduction pathways regulating cell growth and differentiation. Post-translational modifications, including palmitoylation, are critical for the membrane targeting and function of H-Ras. Subcellular localization regulates the signaling pathways engaged by H-Ras activation. We show here that H-Ras is localized at the plasma membrane in caveolin-1-expressing cells but not in caveolin-1-deficient cells. Since palmitoylation is required for trafficking of H-Ras from the endomembrane system to the plasma membrane, we tested whether the altered localization of H-Ras in caveolin-1-null cells is due to decreased H-Ras palmitoylation. Although the palmitoylation profiles of cultured embryo fibroblasts isolated from wild type and caveolin-1 gene-disrupted mice differed, suggesting that caveolin-1, or caveolae, play a role in the palmitate incorporation of a subset of palmitoylated proteins, the palmitoylation of H-Ras was not decreased in caveolin-1-null cells. We conclude that the altered localization of H-Ras in caveolin-1-deficient cells is palmitoylation-independent. This article shows two important new mechanisms by which loss of caveolin-1 expression may perturb intracellular signaling, namely the mislocalization of signaling proteins and alterations in protein palmitoylation. 2009-04-14T00:00:00Z Baran, J. og Mundy, D. I. og Vasanji, A. og Parat, M-O. http://espace.library.uq.edu.au/view/UQ:254445 2011-10-07T00:00:00Z Davis, Felicity og Paraic, Kenny A og Cabot, Peter J. og Roberts-Thomson, Sarah J. og Monteith, Gregory R. http://espace.library.uq.edu.au/view/UQ:261444 2011-11-15T00:00:00Z Rizk, Mariam og Grice, Desma og Roberts-Thomson, Sarah J. og Monteith, Gregory R. http://espace.library.uq.edu.au/view/UQ:144183 2008-06-10T00:00:00Z Roberts-Thomson, S. J.