Besong, AA, Tipper, JL, Ingham, E, Stone, MH, Wroblewski, BM & Fisher, J 1998, 'Quantitative comparison of wear debris from UHMWPE that has and has not been sterilised by gamma irradiation', The Journal of Bone and Joint Surgery, vol. 80, no. 2, pp. 340-344.
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Black, K, Qu, X, Seale, JP & Donnelly, R 1998, 'METABOLIC EFFECTS OF THIOCTIC ACID IN RODENT MODELS OF INSULIN RESISTANCE AND DIABETES', Clinical and Experimental Pharmacology and Physiology, vol. 25, no. 9, pp. 712-714.
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SUMMARY1. The antioxidant thioctic acid (TA) has been used in the treatment of diabetic neuropathy and recent studies have suggested that TA also has pancreatic and peripheral effects that improve glucose transport and metabolism. In the present study, the metabolic effects of TA were evaluated in rodent models of insulin resistance (fructose‐fed Sprague‐Dawley rat) and insulin deficiency (streptozotocin (STZ)‐induced diabetic rat). Oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in conscious rats after treatment with 50 mg/kg per day TA or vehicle for 5 days.2. Fructose feeding for 7 days induced insulin resistance and impaired glucose tolerance and hypertriglycerideaemia. Treatment of fructose‐fed rats with TA had no significant effect on fasting or stimulated glucose levels or on fasting triglyceride concentrations (e.g. the area under the curve for glucose (AUCglu) following OGTT was 1233 ± 67 and 1284 ± 59 in fructose‐fed rats treated with either TA (n= 12) or vehicle (n= 12), respectively). Similarly, TA had no significant effect on IVGTT profiles in fructose‐induced insulin resistance.3. Low‐dose STZ (80 mg/kg, i.p, over 2 days) induced hyper‐glycaemia, but TA had no significant glucose‐lowering effects in STZ‐diabetic rats (AUCglu (OGTT) following oral administration was 5507 ± 27 and 5450 ± 27 in TA (n= 12) and vehicle‐treated (n= 12) rats, respectively). Nor did pretreatment with TA affect the diabetogenic response to STZ.4. In contrast with previous in vitro studies reporting favourable metabolic effects of TA, the present study shows that after short‐term oral therapy there are no significant improvements in glucose tolerance in rodent models of insulin resistance and i...
Chai, C 1998, 'Critical ageing of hydroxyapatite sol–gel solutions', Biomaterials, vol. 19, no. 24, pp. 2291-2296.
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It has been established that hydroxyapatite coatings can be produced using an alkoxide based sol-gel technique. Previous work showed that in addition to hydroxyapatite other phases including CaO were observed. A critical factor in determining the composi
Dahia, PLM, FitzGerald, MG, Zhang, X, Marsh, DJ, Zheng, Z, Pietsch, T, von Deimling, A, Haluska, FG, Haber, DA & Eng, C 1998, 'A highly conserved processed PTEN pseudogene is located on chromosome band 9p21', Oncogene, vol. 16, no. 18, pp. 2403-2406.
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Delatycki, MB, Paris, D, Gardner, RJ, Forshaw, K, Nicholson, GA, Nassif, N, Williamson, R & Forrest, SM 1998, 'Sperm DNA analysis in a Friedreich ataxia premutation carrier suggests both meiotic and mitotic expansion in the FRDA gene.', Journal of Medical Genetics, vol. 35, no. 9, pp. 713-716.
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Donnelly, R & Qu, X 1998, 'MECHANISMS OF INSULIN RESISTANCE AND NEW PHARMACOLOGICAL APPROACHES TO METABOLISM AND DIABETIC COMPLICATIONS', Clinical and Experimental Pharmacology and Physiology, vol. 25, no. 2, pp. 79-87.
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SUMMARY1. Resistance to insulin‐mediated glucose transport and metabolism has been identified as a primary mechanism in the pathogenesis of non‐insulin‐dependent diabetes mellitus (NIDDM) and as a target for drug development. The aetiology of insulin resistance is likely to be multifactorial, but the present review focuses on candidate post‐receptor mechanisms of insulin resistance, particularly protein kinase C (PKC), and the metabolic and genetic significance of β3‐adrenoceptors (β3‐AR) in adipose tissue.2. Multiple lines of evidence suggest that isoform‐selective activation of PKC phosphorylates and down‐regulates one or more substrates involved in glucose transport and metabolism (e.g. glycogen synthase and the insulin receptor) and recent studies have shown increased expression of calcium‐independent isozymes (PKC‐ε and PKC‐θ) in the membrane fraction of skeletal muscle in fructose‐ and fat‐fed rat models of insulin resistance. In addition, there is separate evidence that glucose‐induced PKC activation plays an important role in the micro‐and macrovascular complications of diabetes.3. New pharmacological approaches to NIDDM and obesity have focused on insulin‐sensitizing agents (e.g. troglitazone), β3‐AR agonists, anti‐lipolytic drugs (e.g. the adenosine A1 receptor agonist GR79236) and selective inhibitors of PKC isoforms (e.g. the inhibitor of PKC‐β LY333531). Experimental studies with GR79236 show that this drug ameliorates the hypertriglyceridaemia induced by fructose feeding and that the reduction in fatty acid levels is associated with secondary improvements in glucose tolerance.4. Recent insights into the pathogenesis of NIDDM and its associated complications have been used to develop a range of new therapeutic agents that are currently showing promise in clinical and preclini...
El-Ghundi, M, George, SR, Drago, J, Fletcher, PJ, Fan, T, Nguyen, T, Liu, C, Sibley, DR, Westphal, H & O'Dowd, BF 1998, 'Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior', European Journal of Pharmacology, vol. 353, no. 2-3, pp. 149-158.
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The role of the dopamine D1 receptor subtype in alcohol-seeking behaviors was studied in mice genetically deficient in dopamine D1 receptors (D1-/-). In two-tube free choice limited (1-5 h) and continuous (24 h) access paradigms, mice were exposed to water and increasing concentrations of ethanol (3%, 6% and 12% w/v). Voluntary ethanol consumption and preference over water were markedly reduced in D1-/- mice as compared to heterozygous (D1+/-) and wild-type (D1+/+) controls, whereas overall fluid consumption was comparable. When offered a single drinking tube containing alcohol as their only source of fluid for 24 h, D1-/- mice continued to drink significantly less alcohol than D1+/+ and D1+/- mice. Dopamine D2 receptor blockade with sulpiride caused a small but significant reduction in alcohol intake and preference in D1+/+ mice and attenuated residual alcohol drinking in D1-/- mice. Dopamine D1 receptor blockade with SCH-23390 very effectively reduced alcohol intake in D1+/+ and D1+/- mice to the level seen in untreated D1-/- mice. These findings suggest involvement of both dopamine D1 and D2 receptor mechanisms in alcohol-seeking behavior in mice; however, these implicate D1 receptors as having a more important role in the motivation for alcohol consumption. Copyright (C) 1998 Elsevier Science B.V.
Forrest, SM, Knight, M, Delatycki, MB, Paris, D, Williamson, R, King, J, Yeung, L, Nassif, N & Nicholson, GA 1998, 'The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene', NEUROGENETICS, vol. 1, no. 4, pp. 253-257.
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Garrett, Q, Chatelier, RC, Griesser, HJ & Milthorpe, BK 1998, 'Effect of charged groups on the adsorption and penetration of proteins onto and into carboxymethylated poly(HEMA) hydrogels', BIOMATERIALS, vol. 19, no. 23, pp. 2175-2186.
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Proteins, lipids and other biomolecules interact strongly with the acrylic-based biomaterials used for contact lenses. Although hydrogels are nominally resistant to protein fouling, many studies have reported considerable amounts of protein bound to poly(2-hydroxyethylmethacrylate) (PHEMA) lenses. This study examined the binding of a series of biomolecules (tear protein analogues, mucin and cholesterol) to poly(methylmethacrylate) (PMMA) and three HEMA-based hydrogels (PHEMA, HEMA plus methacrylic acid (P(HEMAMAA)), HEMA plus methacrylic acid plus N-vinylpyrrolidone (P(HEMAMAANVP))) by use of a quartz crystal microbalance with dissipation (QCM-D) monitoring. The QCM-D estimates changes in the mass and viscous constant for the adsorbed layer through measurements of frequency and dissipation. Protein interaction with each of the test materials caused a net increase in mass of the material indicating protein binding except for lysozyme interacting with P(HEMAMAA). A net decrease in mass was observed for lysozyme interacting with P(HEMAMAA) which may be ascribed to lysozyme collapsing the hydrogel by expelling water. A net mass decrease was observed for cholesterol interacting with each of the hydrogel materials, while a mass increase was observed on PMMA.
Gibson, L 1998, 'Melanin and novel melanin precursors from Aeromonas media', FEMS Microbiology Letters, vol. 169, no. 2, pp. 261-268.
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Many bacteria produce reddish brown to black pigments and some of these have been characterised. This report describes the isolation and characterisation of a diffusible brown melanin-like pigment from the bacterium Aeromonas media. Physico-chemical testing suggested that the pigment is a true melanin. New butanol-soluble yellow, red and brown pigments were isolated from the A. media strain under reducing conditions during melanogenesis and these pigments were shown to be unstable precursors of the polymeric brown melanin product. Copyright (C) 1998 Federation of European Microbiological Societies.
Gibson, LF, Woodworth, J & George, AM 1998, 'Probiotic activity of Aeromonas media on the Pacific oyster, Crassostrea gigas, when challenged with Vibrio tubiashii', Aquaculture, vol. 169, no. 1-2, pp. 111-120.
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Gough, A, Sambrook, P, Devlin, J, Huissoon, A, Njeh, C, Robbins, S, Nguyen, T & Emery, P 1998, 'Osteoclastic activation is the principal mechanism leading to secondary osteoporosis in rheumatoid arthritis.', J Rheumatol, vol. 25, no. 7, pp. 1282-1289.
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OBJECTIVE: To use clinical measures and biochemical markers of bone turnover to investigate mechanisms of generalized bone loss in early rheumatoid arthritis (RA). METHODS: We studied 232 patients with RA of less than 2 years' duration and 72 healthy controls using serial dual x-ray absorptiometry scanning of lumbar spine and hips. Patients attended the clinic for clinical and laboratory assessment with storage of serum, urine, and plasma at each visit. Change in bone mineral density (BMD) was calculated for patients and controls and compared with baseline and mean serial values of bone markers over the same intervals. Serum was assayed for procollagen I carboxyterminal propeptide (PICP) and skeletal alkaline phosphatase (sALP); urine for pyridinoline and deoxypyridinoline corrected for creatinine; and plasma for interleukin 1 (IL-1) and IL-6. RESULTS: Patients lost bone significantly faster than controls at all sites (p < 0.01 for all). At first visit patients had significantly lower PICP levels than controls (p < 0.05) and sALP correlated with initial BMD in both patients (p < 0.01, r > 0.35, all sites) and controls (p < 0.0001, r > 0.50, all sites). We rescanned 167 patients at one year and 121 patients at 2 years. Mean urinary pyridinoline and deoxypyridinoline levels correlated strongly with BMD change at all sites, were increased in patients with active disease (p < 0.005), and correlated closely with mean C-reactive protein (CRP) (p < 0.005, r > 0.41 for both). CONCLUSION: This study suggests that osteoclastic activation, rather than suppression of bone formation, is the dominant process leading to bone loss in early RA. Although urinary pyridinoline and deoxypyridinoline were excellent markers of BMD change, CRP was found to be best overall. This provides a rational approach for selecting and treating patients with RA to reduce their established longterm risk of osteoporotic fracture.
Gough, A, Sambrook, P, Devlin, J, Lilley, J, Huisoon, A, Betteridge, J, Franklyn, J, Nguyen, T, Morrison, N, Eisman, J & Emery, P 1998, 'Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis.', J Rheumatol, vol. 25, no. 5, pp. 864-868.
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OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA. METHODS: We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted 'tt', and absence 'TT'. RESULTS: In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics. CONCLUSION: The presence of the VDR gene 't' allele in female patients with RA was associated with accelerated bone loss.
GROSS, KA, CHAI, CS, KANNANGARA, GSK, BEN-NISSAN, B & HANLEY, L 1998, 'Thin hydroxyapatite coatings via sol–gel synthesis', Journal of Materials Science: Materials in Medicine, vol. 9, no. 12, pp. 839-843.
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Production of hydroxyapatite coatings using an alkoxide-based sol-gel route requires control of solution aging time and heating schedule. P-31 nuclear magnetic resonance spectroscopy was used to investigate the changes during aging of the sol and thermal
Ha, QP, Nguyen, HQ, Rye, DC & Durrant-Whyte, HF 1998, 'Sliding mode control with fuzzy tuning for an electro-hydraulic position servo system', International Conference on Knowledge-Based Intelligent Electronic Systems, Proceedings, KES, vol. 1, pp. 141-148.
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This paper presents a novel robust sliding mode controller for a class of nonlinear systems. The control signal consists of an equivalent control to assign desired dynamics to the closed-loop system, a switching control to guarantee a sliding mode, and a fuzzy control to enhance fast tracking and to attenuate chattering. Sufficient conditions for asymptotic tracking are achieved when matching conditions are satisfied. The control method is applied to the position control of an electro-hydraulic servo system. To verify the potential and effectiveness of the proposed controller, simulation results demonstrate its strong robustness against a large range of parameter variations, load disturbance, and nonlinear spring stiffness.
Harris, M, Nguyen, TV, Howard, GM, Kelly, PJ & Eisman, JA 1998, 'Genetic and Environmental Correlations Between Bone Formation and Bone Mineral Density: A Twin Study', Bone, vol. 22, no. 2, pp. 141-145.
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Hoffman, DM, Pallasser, R, Duncan, M, Nguyen, TV & Ho, KKY 1998, 'How Is Whole Body Protein Turnover Perturbed in Growth Hormone-Deficient Adults?1', The Journal of Clinical Endocrinology & Metabolism, vol. 83, no. 12, pp. 4344-4349.
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Adult patients with GH deficiency have reduced lean body mass (LBM), muscle mass, and muscle strength, suggesting an underlying abnormality of protein metabolism. As acute GH administration has previously been reported to decrease protein oxidation and increase protein synthesis in GH-deficient (GHD) adults, we investigated whether the converse might occur in untreated GH deficiency by undertaking studies of whole body protein turnover in 10 GHD and 13 normal subjects using a 3-h primed constant infusion of 1-[13C]leucine. Dual energy x-ray absorptiometry was used to quantify LBM and fat mass (FM). In normal subjects, LBM was the major, independent determinant of leucine appearance (Ra; r = 0.80; P = 0.0009), leucine oxidation (r = 0.81; P = 0.0008), and leucine incorporation into protein (r = 0.75; P = 0.003). However, in an analysis of covariance, FM was also a significant independent determinant of leucine Ra (P = 0.002) and leucine incorporation into protein (P = 0.003). After correcting for LBM and FM, GHD patients had significantly reduced rates of leucine Ra (109.9 ± 4.4 vs. 125.5 ± 3.7 μmol/min, respectively; P = 0.02) and leucine incorporation into protein (87.0 ± 3.9 vs. 100.3 ± 3.3 mmol/min; P = 0.02) compared to normal subjects. There was no significant difference in the corrected rates of leucine oxidation between the two groups (22.9 ± 1.3 vs. 25.2± 1.0, GHD vs. normal; P = 0.20). In summary, GHD adults have reduced rates of protein synthesis and protein breakdown, but normal rates of irreversible oxidative loss; these findings are discordant with what was predicted from the acute changes in protein metabolism observed with GH administration. We conclude that normalization of protein oxidation may be a homeostatic mechanism that operates to constrain protein loss in GHD adults.
Howard, G, Nguyen, T, Morrison, N, Watanabe, T, Sambrook, P, Eisman, J & Kelly, P 1998, 'Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women. Notification of genotype corrections.', J Clin Endocrinol Metab, vol. 83, no. 3, pp. 1043-1043.
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Howard, GM, Nguyen, TV, Harris, M, Kelly, PJ & Eisman, JA 1998, 'Genetic and Environmental Contributions to the Association Between Quantitative Ultrasound and Bone Mineral Density Measurements: A Twin Study', Journal of Bone and Mineral Research, vol. 13, no. 8, pp. 1318-1327.
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Abstract This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 ± 13 years, mean ± SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental ...
Jarrard, DF, Kinoshita, H, Shi, Y, Sandefur, C, Hoff, D, Meisner, LF, Chang, C, Herman, JG, Isaacs, WB & Nassif, N 1998, 'Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells.', Cancer Res, vol. 58, no. 23, pp. 5310-5314.
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Androgen-independent metastatic prostate cancer is characterized by a heterogeneous loss of androgen receptor (AR) expression among tumor cells. In this study, we evaluate DNA hypermethylation as a potential transcriptional regulatory mechanism in AR-negative prostate cancer cell lines. Nucleotide sequence analysis demonstrates an approximately 15-kb CpG island in the AR gene that encompasses the transcription start site and exon 1. Using Southern blotting with methylation-sensitive restriction enzymes and methylation-specific PCR, we find aberrant methylation in the AR expression-negative cell lines Du145, DuPro, TSU-PR1, and PPC1. Incomplete methylation in the AR CpG island is also seen in normal female breast and ovarian tissues consistent with the inactivation of one X chromosome by hypermethylation. In contrast, prostate cancer cell lines LNCaP and PC3 express AR and are unmethylated. Normal prostate epithelial cell strains demonstrate no methylation. Exposure of AR-negative prostate cancer cell lines to 5-aza-2' deoxycytidine, a demethylating agent, induces the reexpression of AR RNA in DuPro and TSU-PR1. This reexpression is associated with a demethylation of this region. Prostate-specific antigen, an androgen-responsive gene, is also specifically induced in these lines after AR reexpression. Therefore, in vitro DNA methylation of the 5' CpG AR island may be associated with the loss of AR expression. Furthermore, our results demonstrate that treatment with demethylating agents may engender the reexpression and function of the androgen receptor in AR-negative cell lines.
Jones, PM & George, AM 1998, 'A New Structural Model for P-Glycoprotein', Journal of Membrane Biology, vol. 166, no. 2, pp. 133-147.
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Multidrug resistance to anti-cancer drugs is a major medical problem. Resistance is manifested largely by the product of the human MDR1 gene, P-glycoprotein, an ABC transporter that is an integral membrane protein of 1280 amino acids arranged into two homologous halves, each comprising 6 putative transmembrane ?-helices and an ATP binding domain. Despite the plethora of data from site-directed, scanning and domain replacement mutagenesis, epitope mapping and photoaffinity labeling, a clear structural model for P-glycoprotein remains largely elusive. In this report, we propose a new model for P-glycoprotein that is supported by the vast body of previous data. The model comprises 2 membrane-embedded 16-strand ?-barrels, attached by short loops to two 6-helix bundles beneath each barrel. Each ATP binding domain contributes 2 ?-strands and 1 ?-helix to the structure. This model, together with an analysis of the amino acid sequence alignment of P-glycoprotein isoforms, is used to delineate drug binding and translocation sites. We show that the locations of these sites are consistent with mutational, kinetic and labeling data.
Kennerson, ML, Nassif, NT & Nicholson, GA 1998, 'Genomic Structure and Physical Mapping ofC17orf1:A Gene Associated with the Proximal Element of the CMT1A-REP Binary Repeat', Genomics, vol. 53, no. 1, pp. 110-112.
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Knepper, M, Milthorpe, BK & Moricca, S 1998, 'Interdiffusion in short-fibre reinforced hydroxyapatite ceramics', JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, vol. 9, no. 10, pp. 589-596.
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Sintering in air and hot isostatic pressing are production methods regarded as being capable of producing fibre-reinforced hydroxyapatite ceramics for biomedical applications. These composites may have the advantage of improved mechanical properties and be suitable for applications in areas where there are significant levels of load on the material. The use of pure hydroxyapatite is restricted to those free of dynamical load. Obtaining improved mechanical strength is a question of the bond between the matrix phase and the fibre-reinforcement phase. However, a chemical bond between both phases, indicated by large diffusion zones, might lead to the dehydration of the hydroxyapatite leading to undesired tricalcium phosphate in the matrix resulting in a weakening of the mechanical and biological stability of the composites. Composites with three fibre types, alumina, 316L-stainless steel and titanium were prepared and sintered in air or hot isostatically pressed. A reaction zone was noted around the titanium and stainless steel fibres, but not around the alumina fibres. The reaction zone was larger for stainless steel than titanium. Hot isostatic pressing also reduced the reaction zone markedly compared to sintering in air.
Kolakowski, LF, O'Neill, GP, Howard, AD, Broussard, SR, Sullivan, KA, Feighner, SD, Sawzdargo, M, Nguyen, T, Kargman, S, Shiao, L, Hreniuk, DL, Tan, CP, Evans, J, Abramovitz, M, Chateauneuf, A, Coulombe, N, Ng, G, Johnson, MP, Tharian, A, Khoshbouei, H, George, SR, Smith, RG & O'Dowd, BF 1998, 'Molecular Characterization and Expression of Cloned Human Galanin Receptors GALR2 and GALR3', Journal of Neurochemistry, vol. 71, no. 6, pp. 2239-2251.
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Abstract: Galanin is a 29‐ or 30‐amino acid peptide with wide‐ranging effects on hormone release, feeding behavior, smooth muscle contractility, and somatosensory neuronal function. Three distinct galanin receptor (GALR) subtypes, designated GALR1, 2, and 3, have been cloned from the rat. We report here the cloning of the human GALR2 and GALR3 genes, an initial characterization of their pharmacology with respect to radioligand binding and signal transduction pathways, and a profile of their expression in brain and peripheral tissues. Human GALR2 and GALR3 show, respectively, 92 and 89% amino acid sequence identity with their rat homologues. Radioligand binding studies with 125I‐galanin show that recombinant human GALR2 binds with high affinity to human galanin (KD = 0.3 nM). Human GALR3 binds galanin with less affinity (IC50 of 12 nM for porcine galanin and 75 nM for human galanin). Human GALR2 was shown to couple to phospholipase C and elevation of intracellular calcium levels as assessed by aequorin luminescence in HEK‐293 cells and by Xenopus melanophore pigment aggregation and dispersion assays, in contrast to human GALR1 and human GALR3, which signal predominantly through inhibition of adenylate cyclase. GALR2 mRNA shows a wide distribution in the brain (mammillary nuclei, dentate gyrus, cingulate gyrus, and posterior hypothalamic, supraoptic, and arcuate nuclei), and restricted peripheral tissue distribution with highest mRNA levels detected in human small intestine. In comparison, whereas GALR3 mRNA was expressed in many areas of the rat brain, there was abundant expression in the primary olfactory cortex, olfactory tubercle, the islands of Calleja, the hippocampal CA regions of Ammon's horn, and the dentate gyrus. GALR3 ...
Lakatos, L, Hutvágner, G & Bánfalvi, Z 1998, 'Potato protein kinase StCPK1: a putative evolutionary link between CDPKs and CRKs', Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, vol. 1442, no. 2-3, pp. 101-108.
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Calcium-dependent protein kinases (CDPKs) in plants are characterized by a four-domain structure including conserved sequences in the catalytic domain, and in the C-terminal calmodulin-like domain. Based on this conservation we have PCR amplified and iso
Marchese, A, Nguyen, T, Malik, P, Xu, S, Cheng, R, Xie, Z, Heng, HHQ, George, SR, Kolakowski, LF & O'Dowd, BF 1998, 'Cloning Genes Encoding Receptors Related to Chemoattractant Receptors', Genomics, vol. 50, no. 2, pp. 281-286.
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We report the cloning of a novel human gene (GPR32) encoding a putative G-protein-coupled receptor (GPCR) of 356 amino acids and a related pseudogene ψGPR32. The deduced amino acid sequence of GPR32 shares 35-39% identity with members of the chemoattractant receptor family. ψGPR32 shares 93% nucleotide identity with GPR32. We identified a mouse EST encoding a putative GPCR (GPR33) of 309 amino acids. The deduced amino acid sequence of GPR33 shares 30-35% identity with members of the chemoattractant receptor family and 36% identity with the receptor encoded by GPR32. The human orthologue of GPR33 contains a single basepair substitution with respect to the mouse, resulting in the presence of an in-frame stop codon within the predicted second intracellular loop, demonstrating that it is a pseudogene. Through fluorescence in situ hybridization and physical mapping of YACs, both GPR32 and ψGPR32 were mapped to chromosomal 19, region q13.3, while ψGPR33 was mapped to chromosome 14q12.
Marsh, DJ, Andrew, SD, Learoyd, DL, Pojer, R, Eng, C & Robinson, BG 1998, 'Deletion-insertion mutation encompassing RET codon 634 is associated with medullary thyroid carcinoma', Human Mutation, vol. 11, no. S1, pp. S3-S4.
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Mazzanti, M, Tonini, R, Valenzuela, S & Breit, SN 1998, 'Molecular Cloning And Functional Expression Of A Novel Nuclear Chloride Ion Channel', Pflugers Archiv-european Journal Of Physiology, vol. 436, no. 5, pp. 1-1.
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McDonnell, I & Darcy, S 1998, 'Tourism precincts: A factor in Bali's rise in fortune and Fiji's fall from favour — an Australian perspective', Journal of Vacation Marketing, vol. 4, no. 4, pp. 353-367.
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The destinations of Fiji and Bali are competi tors in the Australian short-haul sunlust international holiday market. In the period 1982-95 Fiji lost more than half its share of this market with a near corresponding increase in the market share of Bali. This paper explores one of the possible reasons for this dramatic reversal of market shares — the lack of tourism precincts in Fiji. It shows that because of the way that tourism plant developed in Fiji, resorts are isolated and tourism precincts did not develop, in contrast to Bali, which has at least four major tourism precincts. The paper argues that this is one factor in Fiji's declining market Share.
Nguyen, TV 1998, 'Science in Vietnam', Science, vol. 280, no. 5366, pp. 983-983.
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Nguyen, TV, Eisman, JA, Mizunuma, H & Okano, H 1998, 'Does Postmenopausal Bone Loss Occur in Two Phases?', Journal of Bone and Mineral Research, vol. 13, no. 8, pp. 1350-1351.
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Nguyen, TV, Howard, GM, Kelly, PJ & Eisman, JA 1998, 'Bone Mass, Lean Mass, and Fat Mass: Same Genes or Same Environments?', American Journal of Epidemiology, vol. 147, no. 1, pp. 3-16.
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Nguyen, TV, Sambrook, PN & Eisman, JA 1998, 'Bone Loss, Physical Activity, and Weight Change in Elderly Women: The Dubbo Osteoporosis Epidemiology Study', Journal of Bone and Mineral Research, vol. 13, no. 9, pp. 1458-1467.
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Abstract The present study examined the effects of physical activity, weight, and weight change on femoral bone loss in relation to age in elderly women. Baseline and follow-up measurements at an average interval of 2.7 years of femoral neck bone mineral density (BMD) were reanalyzed for 827 women who were part of the Dubbo Osteoporosis Epidemiology Study. Physical activity was assessed based on hours per day spent in each of various activities according to its expected oxygen consumption. The rate of loss of BMD progressively increased with age, i.e., −0.6 ± 0.1, −1.1 ± 0.2, and −2.1 ± 0.6% per year (mean ± SEM) for the 60–69, 70–79, and ≥80 age groups, respectively (p < 0.001). After adjustment for age, physically inactive women lost more (−1.4 ± 0.2% per year; p < 0.001), compared with physically active women (−0.5 ± 0.3% per year; p = 0.15). Thinner women experienced more rapid bone loss, and women whose weight decreased (≥5%) over the study period lost more bone (−1.7 ± 0.4% per year) than those whose weight was stable (−0.8 ± 0.1% per year) or increased (+0.1 ± 0.3% per year; p < 0.01, analysis of variance). Furthermore, women whose BMD was high (>0.81 g/cm2) at baseline experienced greater loss (−1.1 ± 0.2%) compared with those in the middle tertile (1.0 ± 0.2%) or lowest tertile (−0.5 ± 0.3%). Independent predictors of rate of bone loss included age, baseline BMD, weight, weight change, and physical activity; collectively these factors accounted for 13% of total variance of bone loss by multiple regression analysis. It is concluded that a physically active lifestyle and stable weight in the later decades of life may retard proximal femur bone loss and thus contribute to reduction of fracture risk.
O'Dowd, BF, Nguyen, T, Marchese, A, Cheng, R, Lynch, KR, Heng, HHQ, Kolakowski, LF & George, SR 1998, 'Discovery of Three Novel G-Protein-Coupled Receptor Genes', Genomics, vol. 47, no. 2, pp. 310-313.
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We report here the molecular cloning, tissue distribution, and chromosomal localization of novel genes encoding G-protein-coupled receptors (GPCRs). A search of a mouse database of expressed sequence tags revealed an EST partially encoding a GPCR, which was used to screen a mouse genomic library to obtain the translational open reading frame (ORF). The resultant clone, GPR27, contained an intronless ORF, encoding a receptor of 379 amino acids. In an alternate strategy, human genomic DNA was subjected to polymerase chain reaction (PCR) amplification, using degenerate oligonucleotides based on GPR1. Two PCR products partially encoding GPCRs were isolated and used to screen a genomic library to obtain the translational ORF. One of the resultant clones, GPR30, contained an intronless ORF encoding a receptor of 375 amino acids. The other clone, GPR35, also contained an intronless ORF encoding a receptor of 309 amino acids. Transcripts corresponding to GPR27 and GPR30 were detected in several areas of human and rat CNS, while GPR35 expression was detected only in the rat intestine. Through fluorescence in situ hybridization analysis the gene encoding GPR30 was localized to chromosome 7p22 and GPR35 to chromosome 2q37.3.
Paterson, MJ, Paterson, PJK & Ben-Nissan, B 1998, 'The dependence of structural and mechanical properties on film thickness in sol-gel zirconia films', Journal of Materials Research, vol. 13, no. 2, pp. 388-395.
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The structure, morphology, and mechanical properties of sol-gel zirconia films have been examined using XRD, AES depth profiling, AFM, and ultramicro indentation. There is a systematic variation in the structure and morphology of the zirconia films with increasing thickness. These changes include increases in the amount of monoclinic phase, substrate oxides, and a decrease in grain size. Ultramicro indentation measurements indicate measured hardness increases with film thickness. The highest hardness value was 6.12 GPa for a 900 nm thick film. However, these values may be influenced by the substrate oxide layer at the film/substrate interface which increases with film thickness. The modulus of the films appears to be thickness independent. As the films are made up of a number of separately fired layers, it appears that the property changes observed are also related to the number of thermal cycles experienced by the sample.
Payten, WM, Ben-Nissan, B & Mercert, DJ 1998, 'Optimal topology design using a global self-organisational approach', International Journal of Solids and Structures, vol. 35, no. 3-4, pp. 219-237.
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A method based on a self-organisational approach has been developed, where a local state operator defines the state of each finite element at each iteration. The algorithm is based on the principle of local adaptation with global feedback in the form of a derivative equation based on von Mises stresses that allows the local remodelling function to vary at each time step. The state operator has the form of a nonlinear differential equation solved iteratively based on the material density and strain energy density within each element. A constraint equation is formulated based on a maximum deviatoric strain energy criteria, with the objective to minimise the mass of the design domain subject to the above constraint. A number of examples are presented to demonstrate the use of this approach. © 1997 Elsevier Science Ltd.
Randell, AG, Bhalerao, N, Nguyen, TV, Sambrook, PN, Eisman, JA & Silverman, SL 1998, 'Quality of life in osteoporosis: reliability, consistency, and validity of the Osteoporosis Assessment Questionnaire.', J Rheumatol, vol. 25, no. 6, pp. 1171-1179.
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OBJECTIVE: To determine the reliability, consistency, and clinical utility of the Osteoporosis Assessment Questionnaire (OPAQ), an AIMS2 based self-assessment questionnaire. METHODS: Reliability of individual questions, scales, and domains were evaluated in 40 subjects by test-retest and intraclass correlation coefficients and internal consistency by Cronbach's alpha. Construct validity was evaluated by disease state. The relationships between domains and scales were modeled by confirmatory factor analysis. RESULTS: Mean kappa (79 questions) and intraclass correlation (18 health scales) coefficients were 0.58+/-0.16 (mean+/-SD) and 0.82+/-0.07, respectively. Internal consistency was greater than 0.8 in all but 3 scales. Construct validity was confirmed. Patients with hip fracture recorded lower OPAQ scores than patients with vertebral fracture. Correlation and confirmatory factor analyses grouped the 18 health scales into 7 domains. CONCLUSION: These findings suggest that OPAQ is a reliable, consistent, and valid instrument capable of distinguishing hierarchy of functional loss in disease states in osteoporosis.
Rodgers, KJ, Long, C & Jackson, C 1998, 'Cathepsins B, L and S may contribute to the rupture of human atherosclerotic plaques', Heart, vol. 79, no. SUPPL. 1.
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Rupture of the fibrous cap of an atherosclerotic plaque may result in thrombosis and rapid occlusion of the artery. Since the most vulnerable areas of the plaque contain a large number of macrophages, it is thought that the release of matrix-degrading proteinases by these cells may contribute to the weakening and subsequent rupture of the fibrous cap. While a great deal of research has focused on matrix metalloproteinases, cysteine proteinases can also be secreted by activated macrophages. Cathepsin S is unique among the cysteine proteinases in that it is stable at neutral pH. Increased synthesis of cysteine proteinases may result in their secretion from the cell in the pro-form which, unlike the fully processed protein, is stable at neutral pH values. In this study, human atherosclerotic plaques obtained from carotid endarterectomy were dissected into defined regions. Cysteine proteinase levels in each region were assessed using peptide substrates, western blotting and zyrnography. Localisation of these proteinases was then examined histologically. Increased levels of cathepsins B, L and S were found in extracts of the shoulder region (up to 5 fold higher than normal arterial tissue) and close to the lipid core (up to 10 fold higher than normal arterial tissue). Histochemistry using an active site-directed probe revealed that the active proteinases were located in specific sites within these regions. These proteinases are highly active against many matrix molecules, and thus may produce focal weakening of the fibrous cap. Experiments are currently underway in which activated macrophages are incubated with plaque tissue and the effects of a range of proteinase inhibitors on the cleavage of specific matrix molecules examined.
Schnitzler, M, Koorey, D, Dwight, T, Tomaras, C, Macrae, F, Marsh, D & Robinson, B 1998, 'Frequency of codon 1061 and codon 1309 APC mutations in Australian familial adenomatous polyposis patients', Human Mutation, vol. 11, no. S1, pp. S56-S57.
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TASEVSKI, V, BENN, D, PETERS, G, LUTTRELL, B & SIMPSON, ANN 1998, 'The Fischer Rat Thyroid Cell Line FRTL-5 Exhibits a Nondiploid Karyotype', Thyroid, vol. 8, no. 7, pp. 623-626.
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The FRTL-5 cell line is a stable thyroid cell line derived from the thyroid gland of the Fischer rat under defined culture conditions, which has been widely adopted as a model system for the study of thyroid cell function and for bioassay. While characte
Tipper, JL, Ingham, E, Cove, JH, Todd, NJ & Kerr, KG 1998, 'Survival and multiplication of Burkholderia cepacia within respiratory epithelial cells', Clinical Microbiology and Infection, vol. 4, no. 8, pp. 450-459.
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Objective: To investigate the ability of both clinical and environmental strains of Burkholderia cepacia, along with control strains of Pseudomonas aeruginosa and Escherichia coli, to invade a respiratory epithelial cell line, A549. Methods and Results: Using a double immunofluorescence labeling technique, a clinical strain of B. cepacia, C1359, and the clonally related strains A509 and J2315, were shown to invade A549 cells at a high level (2-8% A549 cells invaded) compared to environmental strains of B. cepacia NCTC 10661 and NCTC 10743 (0.5-1% of A549 cells invaded). Control strains of P. aeruginosa PAO1 and E. coli C600 did not appear to be able to invade respiratory epithelial cells using this method. Ceftazidime protection assays revealed that B. cepacia C1359 and NCTC 10743 were able to survive and multiply within A549 cells for > 24 h. In contrast, B. cepacia NCTC 10661, P. aeruginosa PAO1 and E. coli C600 failed to multiply within A549 cells, showing a significant decrease in numbers after 24 h. Conclusions: The ability to survive and multiply within respiratory epithelial cells may be an important virulence factor of B. cepacia infection in cystic fibrosis.
Tuch, BE, Tabiin, MT, Casamento, FM, Simpson, AM & Marshall, GM 1998, 'Transplantation of Genetically Engineered Insulin-Producing Hepatocytes Into Immunoincompetent Mice', Transplantation Proceedings, vol. 30, no. 2, pp. 473-473.
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