Baheiraei, A, Ritchie, JE, Eisman, JA & Nguyen, TV 2005, 'Psychometric properties of the Persian version of the osteoporosis knowledge and health belief questionnaires', Maturitas, vol. 50, no. 2, pp. 134-139.
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Fan, T, Varghese, G, Nguyen, T, Tse, R, O'Dowd, BF & George, SR 2005, 'A Role for the Distal Carboxyl Tails in Generating the Novel Pharmacology and G Protein Activation Profile of μ and δ Opioid Receptor Hetero-oligomers', Journal of Biological Chemistry, vol. 280, no. 46, pp. 38478-38488.
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Opioid receptor pharmacology in vivo has predicted a greater number of receptor subtypes than explained by the profiles of the three cloned opioid receptors, and the functional dependence of the receptors on each other shown in gene-deleted animal models remains unexplained. One mechanism for such findings is the generation of novel signaling complexes by receptor hetero- oligomerization, which we previously showed results in significantly different pharmacology for μ and δ receptor hetero-oligomers compared with the individual receptors. In the present study, we show that deltorphin-II is a fully functional agonist of the μ-δ heteromer, which induced desensitization and inhibited adenylyl cyclase through a pertussis toxin-insensitive G protein. Activation of the μ-δ receptor heteromer resulted in preferential activation of Gαz, illustrated by incorporation of GTPγ35S, whereas activation of the individually expressed μ and δ receptors preferentially activated Gαi. The unique pharmacology of the μ-δ heteromer was dependent on the reciprocal involvement of the distal carboxyl tails of both receptors, so that truncation of the distal μ receptor carboxyl tail modified the δ-selective ligand-binding pocket, and truncation of the δ receptor distal carboxyl tail modified the μ-selective binding pocket. The distal carboxyl tails of both receptors also had a significant role in receptor interaction, as evidenced by the reduced ability to co-immunoprecipitate when the carboxyl tails were truncated. The interaction between μ and δ receptors occurred constitutively when the receptors were co-expressed, but did not occur when receptor expression was temporally separated, indicating that the hetero-oligomers were generated by a co-translational mechanism. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Galvin, AL, Tipper, JL, Ingham, E & Fisher, J 2005, 'Nanometre size wear debris generated from crosslinked and non-crosslinked ultra high molecular weight polyethylene in artificial joints', Wear, vol. 259, no. 7-12, pp. 977-983.
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Hutvagner, G 2005, 'Small RNA asymmetry in RNAi: Function in RISC assembly and gene regulation', FEBS Letters, vol. 579, no. 26, pp. 5850-5857.
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RNAi is a conserved gene‐specific regulatory mechanism, which silences target gene expression transcriptionally and post‐transcriptionally. The RNAi machinery converts the sequence specific information of a long double stranded RNAs (dsRNAs) into small 21–22 nt long dsRNAs (siRNAs, miRNAs) which assemble into an effector complex, the RNA induced silencing complex (RISC). RISC assembly is asymmetric; one strand of an siRNA or a miRNA preferentially incorporates into the RNA–protein complex. Here, I review the rules of the asymmetric RISC formation and discuss their possible regulatory function in several steps in RNAi.
Kwong, RA, Kalish, LH, Nguyen, TV, Kench, JG, Bova, RJ, Cole, IE, Musgrove, EA & Sutherland, RL 2005, 'p14ARF Protein Expression Is a Predictor of Both Relapse and Survival in Squamous Cell Carcinoma of the Anterior Tongue', Clinical Cancer Research, vol. 11, no. 11, pp. 4107-4116.
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Abstract Purpose: The INK4A-ARF locus at chromosome 9p21 is frequently altered in head and neck squamous cell carcinoma (SCC) and encodes two distinct tumor suppressors, p16INK4A and p14ARF. This study addressed the role of p14ARF as a potential prognostic marker in this disease. Experimental Design: p14ARF protein expression was assessed by immunohistochemistry in a cohort of 140 patients with SCC of the anterior tongue. Using univariate and multivariate Cox's proportional hazards models, the outcomes examined were time to disease recurrence or death, with or without clinicopathologic covariates, including nodal status, disease stage, treatment status, Ki-67 staining, and molecular markers with known functional or genetic relationships with p14ARF (p16INK4A, p53, pRb, p21WAF1/CIP1, E2F-1). Results: On multivariate analysis, p14ARF positivity (nucleolar p14ARF staining and/or nuclear p14ARF staining in ≥30% of tumor cells) was an independent predictor of improved disease-free survival (DFS; P = 0.002) and overall survival (OS; P = 0.002). This was further enhanced when p14ARF positivity was cosegregated with positive (≥1%) p16INK4A staining (DFS, P < 0.001; OS, P < 0.001). Patients whose cancers were p14ARF negative and p53 positive (>50%) had the poorest outcome (DFS, P < 0.001; OS, P < 0.001) of any patient subgroup analyzed. Conclusions: These data show that in patients with SCC of the tongue, combined nuclear and nucleolar expression of p14ARF protein predicts for improved DFS and OS independent of established prognostic markers.
Lee, DK, Saldivia, VR, Nguyen, T, Cheng, R, George, SR & O’Dowd, BF 2005, 'Modification of the Terminal Residue of Apelin-13 Antagonizes Its Hypotensive Action', Endocrinology, vol. 146, no. 1, pp. 231-236.
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The apelin peptide is the endogenous ligand for the apelin G protein-coupled receptor. The distribution of the apelin peptides and receptor are widespread in the central nervous system and periphery, with reported roles in the hypothalamic-pituitary-adrenal axis, blood pressure regulation and as one of the most potent positive inotropic substances yet identified. In this report, we show that in native tissues preproapelin exists as a dimer. Dimeric preproapelin was reduced to monomers by dithiothreitol treatment, indicating disulfide linkages. To evaluate the role of the carboxyl-terminal phenylalanine in the hypotensive action of apelin-13, analogs were generated and tested for their role on blood pressure regulation. Injections of apelin-13 and apelin-12 (15 μg/kg) into spontaneously hypertensive rats lowered systolic and diastolic blood pressure to result in decreases of approximately 60% and 15% in mean arterial blood pressure, respectively. Apelin-13(13[d-Phe]) treatment did not differ from apelin-13 in either efficacy or duration of effect, whereas apelin-13(F13A) revealed a loss of function. However, concomitant administration of apelin-13(F13A) (30 μg/kg) blocked hypotensive effects of apelin-13 (15 μg/kg), which revealed that apelin-13(F13A) behaved as an apelin-specific antagonist.
Meier, C, Nguyen, TV, Center, JR, Seibel, MJ & Eisman, JA 2005, 'Bone Resorption and Osteoporotic Fractures in Elderly Men: The Dubbo Osteoporosis Epidemiology Study', Journal of Bone and Mineral Research, vol. 20, no. 4, pp. 579-587.
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Abstract Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. In a case-cohort control study of 151 elderly men followed prospectively over 6.3 years, high bone resorption as assessed by S-ICTP was associated with increased risk of osteoporotic fracture, independent of BMD. Combining measurements of BMD and bone turnover may improve fracture prediction in elderly men. Introduction: Approximately one-third of osteoporotic fractures occur in men. Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. The association between fracture risk and rates of bone turnover has not been well established in men. We examined this relationship in elderly community-dwelling men. Materials and Methods: This case-cohort control study included 50 men with incident low-trauma fractures (cases; age, 72.3 ± 6.7 years) and 101 men without fracture (controls; age, 70.4 ± 4.1 years), who have been prospectively followed in the Dubbo Osteoporosis Epidemiology Study for a median of 6.3 years (range, 2-13 years). BMD at the lumbar spine (LSBMD) and at the femoral neck (FNBMD) and markers of bone turnover were measured at baseline. Bone resorption was assessed by measuring nonfasting serum concentrations of the carboxyterminal cross-linked telopeptide of type I collagen (S-ICTP) and of a linear octapeptide derived from the carboxyterminal type I collagen telopeptide (S-CTX). Bone formation was assessed by measuring the serum levels of the aminoterminal propeptide of type I procollagen (S-PINP). Results: Men with subsequent fractures had lower BMD at baseline, both at the femoral neck and the spine, lower dietary calcium intake, and higher S-ICTP levels than age-and weight-matched controls. Smoking habits, S-CTX, and S-PINP did...
Nelson, AE, Howe, CJ, Nguyen, TV, Seibel, MJ, Baxter, RC, Handelsman, DJ, Kazlauskas, R & Ho, KK 2005, 'Erythropoietin administration does not influence the GH–IGF axis or makers of bone turnover in recreational athletes', Clinical Endocrinology, vol. 63, no. 3, pp. 305-309.
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SummaryObjective Measurement of biochemical markers of the IGF‐system and of collagen turnover is a potential approach to detect GH abuse in sport. These markers are increased in patients on dialysis treated with recombinant human erythropoietin (r‐HuEPO), mimicking the effects of GH. The aim was to determine whether r‐HuEPO induces similar effects on the IGF‐system and collagen turnover in healthy athletes.Subjects and measurements Young male Caucasian recreational athletes were administered 50 U/kg r‐HuEPO (n = 14) or placebo (n = 16) three times a week for 25 days, followed by a 4‐week wash‐out period. IGF‐I, IGFBP‐3, the acid labile subunit (ALS), N‐terminal propeptide of type I collagen (PINP), C‐terminal telopeptide of type I collagen (ICTP) and N‐terminal propeptide of type III collagen (PIIINP) were measured in samples collected at baseline (two samples), after 10, 22 and 24 days of r‐HuEPO treatment and at the end of the 4‐week wash‐out period.Results Treatment with r‐HuEPO resulted in approximately threefold elevation of serum EPO and marked elevation of markers of erythropoiesis. There was no significant treatment effect of r‐HuEPO compared to baseline on IGF‐I, IGFBP‐3, ALS, PINP, ICTP or PIIINP.Conclusions r‐HuEPO administration did not change markers of the IGF‐system and of collagen turnover in young healthy male athletes. Therefore, use of r‐HuEPO in athletes should not affect the validity of a GH doping test using these GH‐responsive markers.
Nguyen, TT, Taylor, PWJ, Redden, RJ & Ford, R 2005, 'Resistance to Ascochyta rabiei (Pass.) Lab. in a wild Cicer germplasm collection', Australian Journal of Experimental Agriculture, vol. 45, no. 10, pp. 1291-1291.
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Cultivated chickpea germplasm collections contain a low frequency of ascochyta blight resistant accessions. This might lead to limitations on the future progress of chickpea breeding worldwide. In an effort to identify novel sources of resistance to ascochyta blight, 56 unique accessions, comprising 8 annual wild Cicer species, were evaluated under a controlled environment that was optimal for infection with an aggressive Australian isolate of Ascochyta rabiei (Pass.) Labrousse. The majority of wild Cicer accessions were either susceptible or highly susceptible to A. rabiei 21 days after inoculation; however, 11 accessions, of which 7 were Cicer judaicum, were resistant. The most resistant accession detected in this study, ATC 46934, together with accessions ATC 46892 and ATC 46935, which were resistant in this and another study, should be targeted for use in future interspecific resistance breeding programs.
Nguyen, TV 2005, 'Pharmacogenetics of anti-resorptive therapy efficacy: a Bayesian interpretation', Osteoporosis International, vol. 16, no. 8, pp. 857-860.
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Nguyen, TV, Esteban, LM, White, CP, Grant, SF, Center, JR, Gardiner, EM & Eisman, JA 2005, 'Contribution of the Collagen I α1 and Vitamin D Receptor Genes to the Risk of Hip Fracture in Elderly Women', The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 12, pp. 6575-6579.
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Nguyen, TV, Nguyen, ND & Ahlborg, HG 2005, 'Risk Assessment and Fracture Discrimination by Ultrasound: The Debate Continues', Journal of Bone and Mineral Research, vol. 20, no. 3, pp. 536-538.
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O'Dowd, BF, Ji, X, Alijaniaram, M, Rajaram, RD, Kong, MMC, Rashid, A, Nguyen, T & George, SR 2005, 'Dopamine Receptor Oligomerization Visualized in Living Cells', Journal of Biological Chemistry, vol. 280, no. 44, pp. 37225-37235.
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G protein-coupled receptors occur as dimers within arrays of oligomers. We visualized ensembles of dopamine receptor oligomers in living cells and evaluated the contributions of receptor conformation to the dynamics of oligomer association and dissociation, using a strategy of trafficking a receptor to another cellular compartment. We incorporated a nuclear localization sequence into the D1 dopamine receptor, which translocated from the cell surface to the nucleus. Receptor inverse agonists blocked this translocation, retaining the modified receptor, D1-nuclear localization signal (NLS), at the cell surface. D1 co-translocated with D1-NLS to the nucleus, indicating formation of homooligomers. (+)-Butaclamol retained both receptors at the cell surface, and removal of the drug allowed translocation of both receptors to the nucleus. Agonist-nonbinding D1(S198A/S199A)-NLS, containing two substituted serine residues in transmembrane 5 also oligomerized with D1, and both were retained on the cell surface by (+)-butaclamol. Drug removal disrupted these oligomerized receptors so that D1 remained at the cell surface while D1(S198A/S199A)-NLS trafficked to the nucleus. Thus, receptor conformational differences permitted oligomer disruption and showed that ligand-binding pocket occupancy by the inverse agonist induced a conformational change. We demonstrated robust heterooligomerization between the D2 dopamine receptor and the D1 receptor. The heterooligomers could not be disrupted by inverse agonists targeting either one of the receptor constituents. However, D2 did not heterooligomerize with the structurally modified D1(S198A/S199A), indicating an impaired interface for their interaction. Thus, we describe a novel method showing that a homogeneous receptor conformation maintains the structural integrity of oligomers, whereas conformational heterogeneity disrupts it. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Pongchaiyakul, C, Kosulwat, V, Rojroongwasinkul, N, Charoenkiatkul, S, Thepsuthammarat, K, Laopaiboon, M, Nguyen, TV & Rajatanavin, R 2005, 'Prediction of Percentage Body Fat in Rural Thai Population Using Simple Anthropometric Measurements', Obesity Research, vol. 13, no. 4, pp. 729-738.
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AbstractObjective: To develop and validate sex‐specific equations for predicting percentage body fat (%BF) in rural Thai population, based on BMI and anthropometric measurements.Research Methods and Procedures: %BF (DXA; GE Lunar Corp., Madison, WI) was measured in 181 men and 255 women who were healthy and between 20 and 84 years old. Anthropometric measures such as weight (kilograms), height (centimeters), BMI (kilograms per meter squared), waist circumference (centimeters), hip circumference (centimeters), thickness at triceps skinfold (millimeters), biceps skinfold (millimeters), subscapular skinfold (millimeters), and suprailiac skinfold (millimeters) were also measured. The sample was randomly divided into a development group (98 men and 125 women) and a validation group (83 men and 130 women). Regression equations of %BF derived from the development group were then evaluated for accuracy in the validation group.Results: The equation for estimating %BF in men was: %BF(men) = 0.42 × subscapular skinfold + 0.62 × BMI − 0.28 × biceps skinfold + 0.17 × waist circumference − 18.47, and in women: %BF(women) = 0.42 × hip circumference + 0.17 × suprailiac skinfold + 0.46 × BMI − 23.75. The coefficient of determination (R2) for both equations was 0.68. Without anthropometric variables, the predictive equation using BMI, age, and sex was: %BF = 1.65 × BMI + 0.06 × age − 15.3 × sex − 10.67 (where sex = 1 for men and sex = 0 for women), with R2 = 0.83. When these equations were applied to the validation sample, the difference between measured and predicted %BF ranged between ±9%, and the positive predictive values were above 0.9.Discussion: These results suggest that simple, n...
Pongchaiyakul, C, Nguyen, ND, Eisman, JA & Nguyen, TV 2005, 'Clinical risk indices, prediction of osteoporosis, and prevention of fractures: diagnostic consequences and costs', Osteoporosis International, vol. 16, no. 11, pp. 1444-1450.
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Pongchaiyakul, C, Nguyen, TV, Foocharoen, C & Rajatanavin, R 2005, 'Estimated volumetric bone mineral density in a rural Thai men and women: Khon Kaen Osteoporosis Study (KKOS).', J Med Assoc Thai, vol. 88 Suppl 5, pp. S46-S52.
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The authors examined the areal bone mineral density (aFNBMD) and estimated volumetric bone mineral density at the femoral neck (vFNBMD) in rural Thai men and women. A total of 181 men and 255 women, between 20 and 84 years of age, living in rural areas of Khon Kaen province, were randomly selected. Areal FNBMD and estimated v FNBMD were determined using dual energy X-ray absorptiometry (DPX-IQ, GE Lunar Corp, Madison, WI). Men had a significantly higher aFNBMD than women, whereas the estimated vFNBMD was similar regardless of sex. The peak for the aFNBMD vs. vFNBMD was observed between 20 and 29 vs. 30 and 39 years of age in men and women, respectively. The prevalence of osteoporosis in men and women using estimated vFNBMD vs. aFNBMD cut-offs was 19 and 14.2 vs 11.8 and 26 percent, respectively. Prevalence increased with age. Estimated vFNBMD shows only small sex-correlated differences in bone density. Estimated vFNBMD was more sensitive than aFNBMD, when used to define the osteoporotic cut-offs in men, while it was less sensitive than aFNBMD in women.
Pongchaiyakul, C, Nguyen, TV, Kosulwat, V, Rojroongwasinkul, N, Charoenkiatkul, S & Rajatanavin, R 2005, 'Effect of urbanization on bone mineral density: A Thai epidemiological study', BMC Musculoskeletal Disorders, vol. 6, no. 1.
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Background: The incidence of fractures in rural populations is lower than in urban populations, although the reason for this difference is unclear. This cross-sectional study was designed to examine the difference in bone mineral density (BMD), a primary predictor of fracture risk, between urban and rural Thai populations. Methods: Femoral neck and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (GE Lunar, Madison, WI) in 411 urban and 436 rural subjects (340 men and 507 women), aged between 20 and 84 years. Body mass index (BMI) was calculated from weight and height. Results: After adjusting for age and body weight in an analysis of covariance model, femoral neck BMD in rural men and women was significantly higher than those in urban men and women (P < 0.001), but the difference was not observed at the lumbar spine. After stratifying by sex, age group, and BMI category, the urban-rural difference in femoral neck BMD became more pronounced in men and women aged <50 years and with BMI ≥ 25 kg/m2. Conclusions: These data suggest that femoral neck BMD in rural men and women was higher than their counterparts in urban areas. This difference could potentially explain part of the urban-rural difference in fracture incidence. © 2005 Pongchaiyakul et al; licensee BioMed Central Ltd.
Pongchaiyakul, C, Nguyen, TV, Kosulwat, V, Rojroongwasinkul, N, Charoenkiatkul, S, Eisman, JA & Rajatanavin, R 2005, 'Contribution of lean tissue mass to the urban-rural difference in bone mineral density', Osteoporosis International, vol. 16, no. 12, pp. 1761-1768.
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Ramírez de Molina, A, Gallego-Ortega, D, Sarmentero, J, Bañez-Coronel, M, Martín-Cantalejo, Y & Lacal, JC 2005, 'Choline Kinase Is a Novel Oncogene that Potentiates RhoA-Induced Carcinogenesis', Cancer Research, vol. 65, no. 13, pp. 5647-5653.
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Abstract Choline kinase is overexpressed in human breast, lung, colorectal, and prostate tumors, a finding that suggests the involvement of this enzyme in carcinogenesis. Here we show that overexpression of choline kinase induce oncogenic transformation of human embryo kidney fibroblasts and canine epithelial Madin-Darby canine kidney cells. Choline kinase lays downstream of RhoA signaling and is activated through ROCK kinase, one of the best-characterized RhoA effectors. In keeping with this, coexpression of RhoA and choline kinase potentiates both anchorage independent growth and tumorigenesis. Finally, choline kinase–mediated transformation is sensitive to MN58b, a well-characterized specific choline kinase inhibitor. These results provide the definitive evidence that choline kinase has oncogenic properties and that choline kinase inhibition constitutes a novel valid antitumor strategy.
So, CH, Varghese, G, Curley, KJ, Kong, MMC, Alijaniaram, M, Ji, X, Nguyen, T, O'Dowd, BF & George, SR 2005, 'D1 and D2 Dopamine Receptors Form Heterooligomers and Cointernalize after Selective Activation of Either Receptor', Molecular Pharmacology, vol. 68, no. 3, pp. 568-578.
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We provided evidence for the formation of a novel phospholipase C-mediated calcium signal arising from coactivation of D1 and D2 dopamine receptors. In the present study, robust fluorescence resonance energy transfer showed that these receptors exist in close proximity indicative of D1-D2 receptor heterooligomerization. The close proximity of these receptors within the heterooligomer allowed for cross-phosphorylation of the D2 receptor by selective activation of the D1 receptor. D1-D2 receptor heterooligomers were internalized when the receptors were coactivated by dopamine or either receptor was singly activated by the D1-selective agonist (±)-6-chloro-7,8-dihydroxy-1- phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) or the D2-selective agonist quinpirole. The D2 receptor expressed alone did not internalize after activation by quinpirole except when coexpressed with the D1 receptor. D1-D2 receptor heterooligomerization resulted in an altered level of steady-state cell surface expression compared with D1 and D2 homooligomers, with increased D2 and decreased D1 receptor cell surface density. Together, these results demonstrated that D1 and D2 receptors formed heterooligomeric units with unique cell surface localization, internalization, and transactivation properties that are distinct from that of D1 and D2 receptor homooligomers. Copyright © 2005 The American Society for Pharmacology and Experimental Therapeutics.
