Kwong, RA, Nguyen, TV, Bova, RJ, Kench, JG, Cole, IE, Musgrove, EA, Henshall, SM & Sutherland, RL 2003, 'Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue.', Clin Cancer Res, vol. 9, no. 10 Pt 1, pp. 3705-3711.
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PURPOSE: Overexpression of E2F-1 is associated with increased invasiveness in head and neck squamous cell carcinoma cell lines in vitro, but its significance in vivo is unknown. This study sought to determine the relationship between E2F-1 and retinoblastoma protein (pRb) expression and disease outcome in squamous cell carcinoma (SCC) of the anterior tongue. EXPERIMENTAL DESIGN: pRb and E2F-1 protein expression was assessed by immunohistochemistry in a cohort of 145 patients with SCC of the anterior tongue. The outcomes examined were time to disease recurrence or death. The relationships between E2F-1 or pRb expression and outcome were assessed by univariate and multivariate Cox's proportional hazards model, with or without clinicopathological covariates, including nodal status, disease stage, treatment status, and molecular markers (cyclin D1, p16(INK4A), and Ki-67) previously measured in this cohort. RESULTS: On univariate analysis, increased expression of E2F-1 (>35% of positive-stained nuclei) was associated with increased disease-free survival (DFS; hazard ratio [HR]: 0.35; P = 0.04) and increased overall survival (OS; HR: 0.33; P = 0.06). Decreased expression of pRb (<50% positive nuclei) was associated with increased DFS (HR: 1.81; P = 0.06) but not with OS (P = 0.11). However, when considered simultaneously with other significant factors, i.e. lymph node status, p16(INK4A) protein expression, and histopathological grade, in the multivariate Cox's proportional hazards model, the additional contributions of E2F-1 and/or pRb expression to DFS and OS were not statistically significant. CONCLUSIONS: These data demonstrate that in patients with SCC of the tongue, overexpression of E2F-1 is associated with increased DFS and OS. However, this association is not independent of lymph node status, tumor grade, and p16(INK4A) expression. Among the cell cycle-regulatory molecules studied, p16(INK4A) expression is the most predictive molecular marker of disease outcome.
Lee, SP, O'Dowd, BF, Rajaram, RD, Nguyen, T & George, SR 2003, 'D2 Dopamine Receptor Homodimerization Is Mediated by Multiple Sites of Interaction, Including an Intermolecular Interaction Involving Transmembrane Domain 4', Biochemistry, vol. 42, no. 37, pp. 11023-11031.
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In this study, we examined the mechanisms of intermolecular interaction involved in D2 dopamine receptor dimer formation to develop an understanding of the quaternary structure of G protein-coupled receptors. The potential role of two mechanisms was investigated: disulfide bridges and hydrophobic interactions between transmembrane domains. D2 dopamine receptor oligomers were unaffected by treatment with a reducing agent; however, oligomers of the D1 dopamine receptor dissociated following a similar treatment. This observation suggested that other forces such as hydrophobic interactions were more robust in the D2 receptor than in the D1 receptor in maintaining oligomerization. To elucidate which transmembrane domains were involved in the intermolecular hydrophobic interactions, truncation mutants were generated by successive deletion of transmembrane domains from amino and/or carboxyl portions of the D2 dopamine receptor. Immunoblot analyses revealed that all the fragments were well expressed but only fragments containing transmembrane domain 4 were able to self-associate, suggesting that critical areas for receptor dimerization resided within this transmembrane domain. Disruption of the helical structure of transmembrane domain 4 in a truncated receptor capable of forming dimers interfered with its ability to self-associate; however, a similar disruption of the transmembrane domain 4 helix structure in the full-length receptor did not significantly affect dimerization. These results indicated that there are other sites of interaction involved in D2 receptor oligomer assembly in addition to transmembrane domain 4.
Nguyen, TV, Livshits, G, Center, JR, Yakovenko, K & Eisman, JA 2003, 'Genetic Determination of Bone Mineral Density: Evidence for a Major Gene', The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 8, pp. 3614-3620.
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Port, L, Center, J, Briffa, NK, Nguyen, T, Cumming, R & Eisman, J 2003, 'Osteoporotic fracture: missed opportunity for intervention', Osteoporosis International, vol. 14, no. 9, pp. 780-784.
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Schwarz, DS, Hutvágner, G, Du, T, Xu, Z, Aronin, N & Zamore, PD 2003, 'Asymmetry in the Assembly of the RNAi Enzyme Complex', Cell, vol. 115, no. 2, pp. 199-208.
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A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5′ ends of the two siRNA strands determine the degree to which each strand participates in the RNAi pathway. siRNA duplexes can be functionally asymmetric, with only one of the two strands able to trigger RNAi. Asymmetry is the hallmark of a related class of small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that single-stranded miRNAs are initially generated as siRNA-like duplexes whose structures predestine one strand to enter the RISC and the other strand to be destroyed. Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis.
Stewart, TD, Tipper, JL, Insley, G, Streicher, RM, Ingham, E & Fisher, J 2003, 'Long‐term wear of ceramic matrix composite materials for hip prostheses under severe swing phase microseparation', Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 66B, no. 2, pp. 567-573.
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AbstractThe purpose of this study was to evaluate the long‐term wear performance of alumina matrix composite (AMC) heads against alumina matrix composite inserts and alumina matrix composite heads against alumina (Al) inserts with the use of a hip‐joint simulator incorporating severe swing phase joint microseparation. The wear of AMC on Al produced an average wear rate of 0.61 mm3/million cycles over the 5‐million‐cycle test duration. The wear of AMC on AMC produced an average wear rate of 0.16 mm3/million cycles over the 5‐million‐cycle test duration. Both the AMC on alumina and AMC on AMC produced significantly lower wear than previously tested HIPed alumina, where an average wear rate of 1.84 mm3/million cycles was reported over 5 million cycles. The wear mechanisms and wear debris of AMC on AMC and AMC on Al were similar to those observed in previous alumina retrieval studies with stripe wear caused by intragranular fracture and wear debris consisting of predominantly uniform 10–20‐nm‐sized particles and a few irregular particles up to 3 μm in size. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 66B: 567–573, 2003
Stewart, TD, Tipper, JL, Insley, G, Streicher, RM, Ingham, E & Fisher, J 2003, 'Severe wear and fracture of zirconia heads against alumina inserts in hip simulator studies with microseparation', The Journal of Arthroplasty, vol. 18, no. 6, pp. 726-734.
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The wear of zirconia femoral heads against alumina acetabular inserts with swing-phase microseparation was investigated in a hip joint simulator. Under mild microseparation conditions, the wear was very low, with an average wear rate of 0.05 mm3/million cycles reported over 5 million cycles of testing. However, under severe microseparation conditions representative of greater joint laxity, the wear rate of zirconia against alumina increased by 2 orders of magnitude, producing severe wear and, in one case, femoral head fracture. The adverse results of this study indicate that the combination of a zirconia femoral head articulating against an alumina acetabular insert is not recommended for clinical use. The results further raise concerns over the suitability of conventional simulators in evaluating the wear of ceramic hip prostheses. © 2003 Elsevier Inc. All rights reserved.
Stewart, TD, Tipper, JL, Insley, G, Streicher, RM, Ingham, E & Fisher, J 2003, 'Severe wear and fracture of zirconia heads against alumina inserts in hip simulator studies with microseparation', JOURNAL OF ARTHROPLASTY, vol. 18, no. 6, pp. 726-734.
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Vanti, WB, Muglia, P, Nguyen, T, Cheng, R, Kennedy, JL, George, SR & O'Dowd, BF 2003, 'Discovery of a null mutation in a human trace amine receptor gene', Genomics, vol. 82, no. 5, pp. 531-536.
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G-protein-coupled receptors (GPCRs) are important mediators of signal transduction, and mutations in GPCR-encoding genes can lead to disease states. Here we describe a null mutation in an orphan GPCR-encoding gene that is predicted to inactivate completely the encoded receptor. The TA3 receptor is a putative member of the recently described mammalian trace amine receptor family, and it is expressed in the pituitary gland and skeletal muscle. We tested for the presence of the mutant form of TA3 (named TA 3-TR) in a normal population, as well as in two disease groups (ADHD and bipolar affective disorder). We found TA3-TR to be commonly expressed in all groups, with ∼20% allele frequency. We did not find any statistically significant correlation between either disease and the presence of TA3-TR.
Vanti, WB, Nguyen, T, Cheng, R, Lynch, KR, George, SR & O’Dowd, BF 2003, 'Novel human G-protein-coupled receptors', Biochemical and Biophysical Research Communications, vol. 305, no. 1, pp. 67-71.
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G-protein-coupled receptors (GPCRs) are important mediators of signal transduction and targets for pharmacological therapeutics. Novel receptor-ligand systems have been discovered through the identification and analysis of orphan GPCRs (oGPCRs). Here we describe the discovery of seven novel human genes encoding oGPCRs. Each novel oGPCR gene was discovered using customized searches of the GenBank genomic databases with previously known GPCR-encoding sequences. The expressed genes can now be used in assays to determine endogenous and pharmacological ligands. GPR133, GPR134, GPR135, GPR136, and GPR137 share identities with a prostate-specific odorant-like GPCR-encoding gene (PSGR). GPR138 and GPR139 share identities with an odorant-like gene derived from human erythroid cells. Transcripts encoding GPR133, GPR134, GPR135, GPR136, and GPR137 were detected in various CNS tissues. The expression of odorant-like genes in non-olfactory tissues requires further clarification, which may be achieved through the search for endogenous cognate ligands for these and other oGPCRs. © 2003 Elsevier Science (USA). All rights reserved.
Williams, S, Tipper, JL, Ingham, E, Stone, MH & Fisher, J 2003, 'In vitro analysis of the wear, wear debris and biological activity of surface-engineered coatings for use in metal-on-metal total hip replacements', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 217, no. 3, pp. 155-163.
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Extremely low wear rates have been reported for metal-on-metal total hip replacements, but concerns remain about the effects of metal ion release, dissolution rates and toxicity. Surface-engineered coatings have the potential to improve wear resistance and reduce the biological activity of the wear debris produced. The aim of this study was to examine the wear and wear debris generation from surface-engineered coatings: titanium nitride (TiN), chromium nitride (CrN) and chromium carbon nitride (CrCN) applied to a cobalt-chrome alloy (CoCr) substrate. The coatings were articulated against themselves in a simple geometry model. The wear particles generated were characterized and the cytotoxic effect on U937 macrophages and L929 fibroblasts assessed. The CrN and CrCN coatings showed a decrease in wear compared to the CoCr bearings and produced small (less than 40 nm in length) wear particles. The wear particles released from the surface engineered bearings also showed a decreased cytotoxic effect on cells compared to the CoCr alloy debris. The reduced wear volumes coupled with the reduced cytotoxicity per unit volume of wear indicate the potential for the clinical application of this technology.
Martinez-Coll, A, Papacosta, C & Nguyen, H 1970, 'Surface electromyography (sEMG) of the sternocleidomastoid (SCM) muscle for variable control using head movement technology', Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439), 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, IEEE, Cancun, Mexico, pp. 1598-1601.
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We have explored the feasibility of an alternative strategy using biological signals such as sEMG of the sternocleidomastoid muscle (SCM) for variable control of our head movement system. Seven volunteers were instrumented with bilateral sEMG sensors on the SCM. Basic neck movements of lateral tilts and graded head rotations were performed. Data were normalized as a percentage of maximum voluntary contractions (MVC) for right and left sides, respectively. The contribution from ipsilateral sEMG signal as percentage of full-range was ?75% for left and 55% for right head tilts. During head rotations at 30, 45, and 60° to both sides, results for sEMG signal amplitude as a percentage of MVC showed excellent reproducibility of the contralateral SCM at approximately 10%, 18%, and 32% on both sides. Despite the small number of subjects for a thorough statistical analysis, no differences exist in t-tests between sEMG (as % of MVC) right and left sides during head rotation; however, differences do exist for each level of rotation (p<0.01). Head rotation provided the most consistent sEMG signal correlation with the degree of motion in all subjects, allowing for reproducible proportional control for our head movement technology.
Martinez-Coll, AA, Morgan, MK & Nguyen, HT 1970, 'Near Infrared Spectroscopy (NIRS) Measurements During Global Cerebral Ischemia in Sheep', Advances in Experimental Medicine and Biology: Oxygen Transport to Tissue XXIII, Oxygen Transport to Tissue, Springer US, Philadelphia, USA, pp. 349-354.
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Stewart, TD, Williams, S, Tipper, JL, Ingham, E, Stone, MH & Fisher, J 1970, 'Advances in simulator testing of orthopaedic joint prostheses', TRIBOLOGICAL RESEARCH AND DESIGN FOR ENGINEERING SYSTEMS, 29th Leeds-Lyon Symposium on Tribology, Elsevier, UNIV LEEDS, BODINGTON HALL, LEEDS, ENGLAND, pp. 291-296.
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