Bell, NH, Morrison, NA, Nguyen, TV, Eisman, J & Hollis, BW 2001, 'Apa I polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men', Journal of Laboratory and Clinical Medicine, vol. 137, no. 2, pp. 133-140.
View/Download from: Publisher's site
Chakraverty, S & Wright, J 2001, 'Adverse events in British hospitals. 'Errors meetings' in radiology did not identify errors leading to complaints and litigation.', BMJ, vol. 322, no. 7299, pp. 1425-1426.
View/Download from: Publisher's site
Endo, MM, Barbour, PS, Barton, DC, Fisher, J, Tipper, JL, Ingham, E & Stone, MH 2001, 'Comparative wear and wear debris under three different counterface conditions of crosslinked and non-crosslinked ultra high molecular weight polyethylene.', Biomed Mater Eng, vol. 11, no. 1, pp. 23-35.
View description>>
The wear debris generated from ultra high molecular weight polyethylene (UHMWPE) have been recognised as one of the major causes of failure in total hip replacements (THR). It is essential to reduce the wear debris generated from UHMWPE acetabular cups in order to minimise this problem. Debris in the submicron size range is believed to have greater osteolytic potential. It is now known that crosslinked UHMWPE acetabular cups have reduced volumetric wear rates but little is known about the influence of crosslinking on the size and morphology of the wear debris. In this study, the wear of grade GUR 1020 crosslinked (vacuum gamma irradiated), GUR 1120 crosslinked (acetylene enhanced irradiated) and non cross linked (ethylene oxide sterilised) GUR 1020 UHMWPE was compared in multidirectional pin-on-plate wear tests under three different counterface conditions (smooth, isotropically rough and scratched counterfaces). Multidirectional motion was chosen because this motion was closer to the relative motion in the natural hip. From this study, better wear resistance of crosslinked UHMWPE compared with non-crosslinked UHMWPE was demonstrated for the smooth counterface conditions. However, in the rough and scratched counterface conditions, the vacuum gamma irradiated crosslinked material produced significantly higher wear rates than the non-crosslinked material. The analysis of the wear debris showed that the majority of the volume of the acetylene enhanced crosslinked UHMWPE wear debris was in the most biologically active size range (0.1 to 0.5 microm). In contrast, the non-crosslinked material and the vacuum gamma irradiated crosslinked material had a greater proportion of the volume of the debris in the larger size ranges which are less biologically active. This has important implications for its osteolytic potential.
Firkins, PJ, Tipper, JL, Ingham, E, Stone, MH, Farrar, R & Fisher, J 2001, 'A novel low wearing differential hardness, ceramic-on-metal hip joint prosthesis', Journal of Biomechanics, vol. 34, no. 10, pp. 1291-1298.
View/Download from: Publisher's site
Firkins, PJ, Tipper, JL, Ingham, E, Stone, MH, Farrar, R & Fisher, J 2001, 'Influence of simulator kinematics on the wear of metal-on-metal hip prostheses', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 215, no. 1, pp. 119-121.
View/Download from: Publisher's site
View description>>
There is now considerable interest in metal-on-metal bearings for hip prostheses. Extremely low wear rates (0.1 mm3/106 cycles) have been reported in some simulator studies, while in vivo studies, although still very low, have shown wear rates of the order of 1 mm3/106 cycles. The aim of this study was to compare wear rates of metal-on-metal bearings in two hip simulators with different kinematic inputs. In the simulator with three independent input motions which produced an open elliptical wear path with a low level of eccentricity, the wear rates were very low as recorded previously in other simulators. In the simulator with two input motions which produced an open elliptical wear path with greater eccentricity the wear rate was at least ten times higher and closer to clinical values. The motion and kinematic conditions in the contact are critical determinants of wear in metal-on-metal bearings.
Firkins, PJ, Tipper, JL, Saadatzadeh, MR, Ingham, E, Stone, MH, Farrar, R & Fisher, J 2001, 'Quantitative analysis of wear and wear debris from metal-on-metal hip prostheses tested in a physiological hip joint simulator.', Biomed Mater Eng, vol. 11, no. 2, pp. 143-157.
View description>>
Osteolysis and loosening of artificial joints caused by UHMWPE wear debris has prompted renewed interest in metal-on-metal (MOM) hip prostheses. This study investigated the wear and wear debris morphology generated by MOM prostheses in a physiological anatomical hip simulator for different carbon content cobalt chrome alloys. The low carbon pairings demonstrated significantly higher 'bedding in' and steady state wear rates than the mixed and high carbon pairings. The in vitro wear rates reported here were up to one or two orders of magnitude lower than the clinical wear rates for first-generation MOM hip prostheses. Two methods for characterising the metal wear debris were developed, involving digestion, scanning electron microscopy and transmission electron microscopy. The metal wear particles characterised by the two methods were similar in size, 25-36 nm, and comparable to particles isolated from periprosthetic tissues from first and second-generation MOM hip prostheses. Due to the small size of the metal particles, the number of particles generated per year for MOM prostheses in vitro was estimated to be up to 100 times higher than the number of polyethylene particles generated per year in vivo. The volumetric wear rates were affected by the carbon content of the cobalt chrome alloy and the material combinations used. However, particle size and morphology was not affected by method of particle characterisation, the carbon content of the alloy or material combination.
Harris, M, Hauser, S, Nguyen, TV, Kelly, PJ, Rodda, C, Morton, J, Freezer, N, Strauss, BJG, Eisman, JA & Walker, JL 2001, 'Bone mineral density in prepubertal asthmatics receiving corticosteroid treatment', Journal of Paediatrics and Child Health, vol. 37, no. 1, pp. 67-71.
View/Download from: Publisher's site
View description>>
Objective: To examine whether bone mass is reduced in prepubertal, asthmatics receiving high doses of inhaled corticosteroids. Methodology: A cross‐sectional comparison of lumbar spine‐bone mineral density (LS‐BMD) was undertaken in 76 subjects after stratifying them according to dosage and administration route of corticosteroid. Results: Weight was the only independent predictor of LS‐BMD (r2 = 0.38). Children receiving greater than 800 μg/day of inhaled corticosteroid plus intermittent oral corticosteroid had a significantly lower weight‐adjusted LS‐BMD than children treated with 400–800 μg/day of inhaled corticosteroid (mean difference: 0.06 g/cm2, 95% confidence interval (CI): – 0.02 to – 0.10). A significant difference in weight‐adjusted LS‐BMD persisted when all children receiving greater than 800 μg/day of inhaled corticosteroid, irrespective of additional oral corticosteroid treatment, were compared with children receiving 400–800 μg/day of inhaled corticosteroid (mean difference: – 0.05 g/cm2, 95%CI interval: –0.02 to – 0.09). Bone mass was similar in children not receiving any inhaled corticosteroid and those treated with 400–800 μg/day of inhaled corticosteroid. Conclusions: A reduced bone mass in prepubertal asthmatic children receiving high doses of inhaled corticosteroids may predetermine a compromised peak bone mass and increase osteoporotic fracture risk in adulthood.
Howling, GI, Barnett, PI, Tipper, JL, Stone, MH, Fisher, J & Ingham, E 2001, 'Quantitative characterization of polyethylene debris isolated from periprosthetic tissue in early failure knee implants and early and late failure Charnley hip implants', Journal of Biomedical Materials Research, vol. 58, no. 4, pp. 415-420.
View/Download from: Publisher's site
View description>>
AbstractThis study isolated and characterized UHMWPE particles from 3 explant groups: early Charnley hip failures (ECE; < 10 years), late Charnley hip failures (LCE; > 10 years) and early knee failures (EKE; < 10 years). Debris isolated from the 3 groups had percentage particle number and percentage volumetric concentration distributions that were not significantly different. The greatest number of particles were found in the 0.1–0.5 μm size range and 19–20.6% of the volumetric concentration was below 1 μm in size in all groups. However, there were significant differences in the total volumetric concentration of debris isolated per g of tissue. LCE had significantly higher volumes of debris than ECE and EKE, there was no significant difference in the volume of debris from the EKE and ECE. The mean aspect ratio and mean irregularity ratio of the LCE group were also significantly higher than the ECE and EKE, suggesting that different wear mechanisms were occurring in the late Charnley group compared to the early Charnley and knee groups. These results also suggest that early knees, with normal surface wear, may have similar wear mechanisms to early Charnley hips and indicate that similar volumes of biologically active micrometer and sub‐micrometer UHMWPE particles were produced. This may have important implications in the longer‐term outcome of total knee arthroplasties, because it indicates a similar potential for osteolysis induced by wear debris. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 415–420, 2001
Hutvágner, G, Bánfalvi, Z, Milánkovics, I, Silhavy, D, Polgár, Z, Horváth, S, Wolters, P & Nap, J-P 2001, 'Molecular markers associated with leptinine production are located on chromosome 1 in Solanum chacoense', Theoretical and Applied Genetics, vol. 102, no. 6-7, pp. 1065-1071.
View/Download from: Publisher's site
View description>>
Leptines of Solanum chacoense are effective natural deterrents against the Colorado potato beetle. Leptines are the acetylated forms of the glycoalkaloids solanine and chaconine and are supposed to be synthesised via hydroxylated derivatives, called leptinines. Inheritance of leptinine production was studied in crosses of closely related S. chacoense genotypes. The segregation data supported a single-gene model for the inheritance of leptinine production. In the segregating F1 population of a S. chacoense cross, AFLP, RFLP and RAPD markers segregating with the leptinine production have been identified. The locus involved in leptinine synthesis was localised to the short arm of chromosome 1 of the potato where a major QTL for solanidine production, and markers with tight linkage to leptine production, have been mapped before. Our data further support the previous finding that the short arm of chromosome 1 is involved in steroid alkaloid synthesis in potato, and suggest that the genes involved in leptinine and leptine production are tightly linked in S. chacoense.
Hutvágner, G, McLachlan, J, Pasquinelli, AE, Bálint, E, Tuschl, T & Zamore, PD 2001, 'A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA', Science, vol. 293, no. 5531, pp. 834-838.
View/Download from: Publisher's site
View description>>
The 21-nucleotide small temporal RNA (stRNA) let-7 regulates developmental timing in Caenorhabditis elegans and probably in other bilateral animals. We present in vivo and in vitro evidence that in Drosophila melanogaster a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let-7 stRNA. Targeted destruction in cultured human cells of the messenger RNA encoding the enzyme Dicer, which acts in the RNA interference pathway, leads to accumulation of the let-7 precursor. Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression.
Im, D-S, Heise, CE, Nguyen, T, O'Dowd, BF & Lynch, KR 2001, 'Identification of a Molecular Target of Psychosine and Its Role in Globoid Cell Formation', The Journal of Cell Biology, vol. 153, no. 2, pp. 429-434.
View/Download from: Publisher's site
View description>>
Globoid cell leukodystrophy (GLD) is characterized histopathologically by apoptosis of oligodendrocytes, progressive demyelination, and the existence of large, multinuclear (globoid) cells derived from perivascular microglia. The glycosphingolipid, psychosine (d-galactosyl-β-1,1′ sphingosine), accumulates to micromolar levels in GLD patients who lack the degradative enzyme galactosyl ceramidase. Here we document that an orphan G protein–coupled receptor, T cell death–associated gene 8, is a specific psychosine receptor. Treatment of cultured cells expressing this receptor with psychosine or structurally related glycosphingolipids results in the formation of globoid, multinuclear cells. Our discovery of a molecular target for psychosine suggests a mechanism for the globoid cell histology characteristic of GLD, provides a tool with which to explore the disjunction of mitosis and cytokinesis in cell cultures, and provides a platform for developing a medicinal chemistry for psychosine.
Lee, DK, George, SR, Cheng, R, Nguyen, T, Liu, Y, Brown, M, Lynch, KR & O’Dowd, BF 2001, 'Identification of four novel human G protein-coupled receptors expressed in the brain', Molecular Brain Research, vol. 86, no. 1-2, pp. 13-22.
View/Download from: Publisher's site
View description>>
We report the discovery and tissue distributions of four novel human genes, GPR61, GPR62, GPR63 and GPR77, all of which encode G protein-coupled receptors (GPCRs). GPR61 was discovered in a search of the patent literature which retrieved a rabbit DNA sequence partially encoding a novel GPCR. This sequence was used to obtain a full-length human cDNA encoding GPR61, a receptor of 417 amino acid length. A search of the GenBank genomic sequence databases revealed three previously unrecognized intronless genes encoding the orphan GPCrs (oGPCRs) GPR62, GPR63 and GPR77, with respective amino acid lengths of 368, 419 and 337. Sequence analysis revealed that GPR61 and GPR62, and a published orphan receptor p47MNR, shared the highest level of identities to each other, ranging from 36 to 45% in the transmembrane (TM) domains. Together, these three oGPCRs appear to comprise a novel subfamily of GPCRs, most closely related to the serotonin 5-HT6 receptor. Sequence analysis of GPR63 and GPR77 revealed highest sequence identities in the TM regions with the oGPCR PSP24 (58%) and the anaphylatoxin C5a receptor (49%) respectively. Tissue distribution analyses detected the expression of all four novel genes in the human brain. GPR61 mRNA expression was detected in the caudate, putamen and thalamus of human brain, with a more widespread expression pattern in rat brain, with mRNA signals in areas of the cortex, hippocampus, thalamus, hypothalamus and midbrain. GPR62 mRNA expression was detected in the basal forebrain, frontal cortex, caudate, putamen, thalamus and hippocampus. GPR63 mRNA expression was detected in the frontal cortex, with lower levels in the thalamus, caudate, hypothalamus and midbrain. Analysis of GPR77 mRNA expression revealed signals in the frontal cortex, hippocampus and hypothalamus with high transcript levels in the liver. © 2001 Elsevier Science B.V.
Lee, DK, Nguyen, T, Lynch, KR, Cheng, R, Vanti, WB, Arkhitko, O, Lewis, T, Evans, JF, George, SR & O'Dowd, BF 2001, 'Discovery and mapping of ten novel G protein-coupled receptor genes', Gene, vol. 275, no. 1, pp. 83-91.
View/Download from: Publisher's site
View description>>
We report the identification, cloning and tissue distributions of ten novel human genes encoding G protein-coupled receptors (GPCRs) GPR78, GPR80, GPR81, GPR82, GPR93, GPR94, GPR95, GPR101, GPR102, GPR103 and a pseudogene, ψGPR79. Each novel orphan GPCR (oGPCR) gene was discovered using customized searches of the GenBank high-throughput genomic sequences database with previously known GPCR-encoding sequences. The expressed genes can now be used in assays to determine endogenous and pharmacological ligands. GPR78 shared highest identity with the oGPCR gene GPR26 (56% identity in the transmembrane (TM) regions). ψGPR79 shared highest sequence identity with the P2Y2 gene and contained a frame-shift truncating the encoded receptor in TM5, demonstrating a pseudogene. GPR80 shared highest identity with the P2Y1 gene (45% in the TM regions), while GPR81, GPR82 and GPR93 shared TM identities with the oGPCR genes HM74 (70%), GPR17 (30%) and P2Y5 (40%), respectively. Two other novel GPCR genes, GPR94 and GPR95, encoded a subfamily with the genes encoding the UDP-glucose and P2Y12 receptors (sharing >50% identities in the TM regions). GPR101 demonstrated only distant identities with other GPCR genes and GPR102 shared identities with GPR57, GPR58 and PNR (35-42% in the TM regions). GPR103 shared identities with the neuropeptide FF 2, neuropeptide Y2 and galanin GalR1 receptors (34-38% in the TM regions). Northern analyses revealed GPR78 mRNA expression in the pituitary and placenta and GPR81 expression in the pituitary. A search of the GenBank databases with the GPR82 sequence retrieved an identical sequence in an expressed sequence tag (EST) partially encoding GPR82 from human colonic tissue. The GPR93 sequence retrieved an identical, human EST sequence from human primary tonsil B-cells and an EST partially encoding mouse GPR93 from small intestinal tissue. GPR94 was expressed in the frontal cortex, caudate putamen and thalamus of brain while GPR95 was expressed in the huma...
Nguyen, T, Shapiro, DA, George, SR, Setola, V, Lee, DK, Cheng, R, Rauser, L, Lee, SP, Lynch, KR, Roth, BL & O'Dowd, BF 2001, 'Discovery of a Novel Member of the Histamine Receptor Family', Molecular Pharmacology, vol. 59, no. 3, pp. 427-433.
View/Download from: Publisher's site
View description>>
We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [3H]histamine (Kd = 44 nM) and [3H]pyrilamine(Kd = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (Ki range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.
Nguyen, TV 2001, 'Adverse events in British hospitals', BMJ, vol. 322, no. 7299, pp. 1425-1425.
View/Download from: Publisher's site
Nguyen, TV 2001, 'Risk Factors for Proximal Humerus, Forearm, and Wrist Fractures in Elderly Men and Women The Dubbo Osteoporosis Epidemiology Study', American Journal of Epidemiology, vol. 153, no. 6, pp. 587-595.
View/Download from: Publisher's site
Nguyen, TV & Sambrook, PN 2001, 'Clinical role of quantitative ultrasound in the assessment of osteoporosis in individual patients', Medical Journal of Australia, vol. 174, no. 6, pp. 310-311.
View/Download from: Publisher's site
Nguyen, TV, Maynard, LM, Towne, B, Roche, AF, Wisemandle, W, Li, J, Guo, SS, Chumlea, WC & Siervogel, RM 2001, 'Sex Differences in Bone Mass Acquisition During Growth', Journal of Clinical Densitometry, vol. 4, no. 2, pp. 147-157.
View/Download from: Publisher's site
Tipper, JL, Firkins, PJ, Besong, AA, Barbour, PSM, Nevelos, J, Stone, MH, Ingham, E & Fisher, J 2001, 'Characterisation of wear debris from UHMWPE on zirconia ceramic, metal-on-metal and alumina ceramic-on-ceramic hip prostheses generated in a physiological anatomical hip joint simulator', Wear, vol. 250, no. 1-12, pp. 120-128.
View/Download from: Publisher's site
Törjék, O, Kiss, E, Mázik-Tőkei, K, Hutvágner, G, Silhavy, D, Bánfalvi, Z, Kertész, Z, Pauk, J & Heszky, L 2001, 'Comparative Molecular Analysis of Winter Wheat Cultivars and Their Doubled Haploid Derivatives', Cereal Research Communications, vol. 29, no. 1-2, pp. 41-48.
View/Download from: Publisher's site
View description>>
Genetic stability of doubled haploid (DH) lines of androgenetic origin is the prerequisite of their breeding value. In our investigations GK Gobe: a traditional cultivar, GK Delibab: a cultivar of doubled haploid origin, various DH lines of GK Gobe (firs
Zozulya, S, Echeverri, F & Nguyen, T 2001, 'The human olfactory receptor repertoire', Genome Biology, vol. 2, no. 6, pp. research0018.1-research0018.1.
View/Download from: Publisher's site
View description>>
BACKGROUND: The mammalian olfactory apparatus is able to recognize and distinguish thousands of structurally diverse volatile chemicals. This chemosensory function is mediated by a very large family of seven-transmembrane olfactory (odorant) receptors encoded by approximately 1,000 genes, the majority of which are believed to be pseudogenes in humans. RESULTS: The strategy of our sequence database mining for full-length, functional candidate odorant receptor genes was based on the high overall sequence similarity and presence of a number of conserved sequence motifs in all known mammalian odorant receptors as well as the absence of introns in their coding sequences. We report here the identification and physical cloning of 347 putative human full-length odorant receptor genes. Comparative sequence analysis of the predicted gene products allowed us to identify and define a number of consensus sequence motifs and structural features of this vast family of receptors. A new nomenclature for human odorant receptors based on their chromosomal localization and phylogenetic analysis is proposed. We believe that these sequences represent the essentially complete repertoire of functional human odorant receptors. CONCLUSIONS: The identification and cloning of all functional human odorant receptor genes is an important initial step in understanding receptor-ligand specificity and combinatorial encoding of odorant stimuli in human olfaction.
