Ammit, A 2000, 'Antagonist of chemokine receptors CCR1 and CCR3', Respiratory Research, vol. 2, no. 1.
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AMMIT, AJ, ARMOUR, CL & BLACK, JL 2000, 'Smooth-Muscle Myosin Light-Chain Kinase Content Is Increased in Human Sensitized Airways', American Journal of Respiratory and Critical Care Medicine, vol. 161, no. 1, pp. 257-263.
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Ammit, AJ, Hoffman, RK, Amrani, Y, Lazaar, AL, Hay, DWP, Torphy, TJ, Penn, RB & Panettieri, RA 2000, 'Tumor Necrosis Factor- α –Induced Secretion of RANTES and Interleukin-6 from Human Airway Smooth-Muscle Cells', American Journal of Respiratory Cell and Molecular Biology, vol. 23, no. 6, pp. 794-802.
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Ayre, PJ, Vidakovic, SS, Tansley, GD, Watterson, PA & Lovell, NH 2000, 'Sensorless Flow and Head Estimation in the VentrAssist Rotary Blood Pump', Artificial Organs, vol. 24, no. 8, pp. 585-588.
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Abstract: Flow rate and pressure difference (or head) are key variables needed in the control of implantable rotary blood pumps. However, use of flow and/or pressure probes can decrease reliability and increase system power consumption and expense. For a given fluid viscosity, the flow state is determined by any 2 of the 4 pump variables: Flow, pressure difference, speed, and motor input power can be used. Thus, if viscosity is known or if its influence is sufficiently small, flow rate and pressure difference can be estimated from the motor speed and motor input power. For the VentrAssist centrifugal blood pump, which uses a hydrodynamic bearing, sensorless flow and pressure head estimation accuracy of 2 of our impeller designs were compared for a viscosity range of 1.2 to 4.5 mPas. This showed impeller design optimization can improve estimation accuracy. We also compared estimation accuracy using 2 blood analogues used in vitro, aqueous glycerol and red blood cells suspended in Haemaccel. The nature of the blood analogue and not only the viscosity of the fluid seems to influence estimation accuracy in our pump.
Bell, J, Besong, AA, Tipper, JL, Ingham, E, Wroblewski, BM, Stone, MH & Fisher, J 2000, 'Influence of gelatin and bovine serum lubricants on ultra-high molecular weight polyethylene wear debris generated in in vitro simulations', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 214, no. 5, pp. 513-518.
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Ultra-high molecular weight polyethylene (UHMWPE) wear debris induced osteolysis has a major role in the late aseptic loosening and ultimate failure of total hip replacements (THR). Clinically relevant in vitro simulations of wear are essential to predict the osteolytic potential of bearing surfaces in artificial hip joints. Newborn calf or bovine serum has been accepted as a boundary lubricant for such in vitro tests, but its biological stability has been questioned. This study compared the wear factors, number of wear particles and levels of microbial contamination produced in bovine serum and a gelatin-based lubricant. The wear factors produced by the two lubricants were not significantly different, however the wear debris morphology produced was substantially different. The bovine serum became contaminated with micro-organisms within 28 h, whereas the protein-based lubricant remained uncontaminated. The results showed that bovine serum was not a stable boundary lubricant. They also showed that although the wear factors for the two solutions were not significantly different, the protein-based lubricant was not a suitable alternative to bovine serum because the wear debris produced was not clinically relevant.
Benn, DE, Dwight, T, Richardson, AL, Delbridge, L, Bambach, CP, Stowasser, M, Gordon, RD, Marsh, DJ & Robinson, BG 2000, 'Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p.', Cancer Res, vol. 60, no. 24, pp. 7048-7051.
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Pheochromocytomas are tumors of the adrenal medulla originating in the chromaffin cells derived from the neural crest. Ten % of these tumors are associated with the familial cancer syndromes multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and rarely, neurofibromatosis type 1, in which germ-line mutations have been identified in RET, VHL, and NF1, respectively. In both the sporadic and familial form of pheochromocytoma, allelic loss at 1p, 3p, 17p, and 22q has been reported, yet the molecular pathogenesis of these tumors is largely unknown. Allelic loss at chromosome 1p has also been reported in other endocrine tumors, such as medullary thyroid cancer and tumors of the parathyroid gland, as well as in tumors of neural crest origin including neuroblastoma and malignant melanoma. In this study, we performed fine structure mapping of deletions at chromosome 1p in familial and sporadic pheochromocytomas to identify discrete regions likely housing tumor suppressor genes involved in the development of these tumors. Ten microsatellite markers spanning a region of approximately 70 cM (1pter to 1p34.3) were used to screen 20 pheochromocytomas from 19 unrelated patients for loss of heterozygosity (LOH). LOH was detected at five or more loci in 8 of 13 (61%) sporadic samples and at five or more loci in four of five (80%) tumor samples from patients with multiple endocrine neoplasia type 2. No LOH at 1p was detected in pheochromocytomas from two VHL patients. Analysis of the combined sporadic and familial tumor data suggested three possible regions of common somatic loss, designated as PC1 (D1S243 to D1S244), PC2 (D1S228 to D1S507), and PC3 (D1S507 toward the centromere). We propose that chromosome 1p may be the site of at least three putative tumor suppressor loci involved in the tumorigenesis of pheochromocytomas. At least one of these loci, PC2 spanning an interval of <3.8 cM, is likely to have a broader role in the development of endocrine malignancies.
Cadd, A, Keatinge, D, Henssen, M, O’Brien, L, Parker, D, Rohr, Y, Schneider, J & Thompson, J 2000, 'Assessment and documentation of bowel care management in palliative care: incorporating patient preferences into the care regimen', Journal of Clinical Nursing, vol. 9, no. 2, pp. 228-235.
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• Nurses in a palliative care unit (PCU) recognized that there were several inconsistencies relating to assessment and documentation of patient preferences in bowel care management.• Although bowel care is recognized as of key importance to the wellbeing of palliative care patients, there is little evidence in current literature about accommodation of patient preferences in bowel care management.• A questionnaire was developed to assess whether patient preferences were elicited on admission to the PCU, were documented, and were included in the bowel care regimen.• Data were collected from 100 patients in two PCUs in Australia.• The findings suggested that little was assessed or documented about bowel care management on admission except functional or pharmacological information.• According to patients in the study, their preferences were seldom incorporated into the bowel care regimen. Lack of documentation of bowel care preferences was also found following an audit of patient notes.• Techniques for eliciting information, awareness of alternative or complementary methods of bowel care and better documentation procedures are all recommended for inclusion in nursing practice in the palliative care setting.
Coutts, AJ & Reaburn, PR 2000, 'Time and motion analysis of the AFL field umpire. Australian Football League.', J Sci Med Sport, vol. 3, no. 2, pp. 132-139.
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The purpose of the present study was to quantify the movement patterns and work intensities of field umpires while officiating in the three-umpire system of the Australian Football League (AFL). Five umpires were randomly selected and videoed throughout five AFL-matches played at the Brisbane Cricket Ground. Each video was analysed manually for time spent in each of four movement modalities: forward, backward, sideways and stationary which were further analysed into the categories of forward sprinting, forward cruising/jogging and forward walking; backward fast/moderate and backward slow; sideways movement and stationary. The following calculations were made: a) the total time spent performing each movement modality; b) the relative contribution (%) of time spent in each activity; and c) the work to rest ratio. The relative time contribution of each movement modality was: Sprinting (1.9+/-0.2%), Cruising/Jogging (26.1+/-3.2%), Walking (21.9+/-3.1%). Fast/Moderate Backward (14.6+/-1.2%), Slow Backward (13.6+/-1.0%), Sideways (2.2+/-0.3%) and Stationary (19.7+/-2.7%). The average time of effort for each movement modality were found to be: Sprinting (2.2+/-0.4 secs), Cruising/Jogging (6.09+/-1.3 secs), Walking (9.9+/-1.1 secs), Backward Fast/Moderate (4.4+/-0.3 secs), Backward Slow (5.2+/-0.8 secs), Sideways (1.7+/-0.1 secs) and Stationary (7.4+/-1.4 secs). The average work to rest ratio was approximately between 1:4-1:5. The current findings provide a detailed description of the movement patterns and work intensities of AFL field umpires which may be used in the development of training programs specific to the three-umpire system.
Coutts, AJ & Reaburn, PRJ 2000, 'Time and motion analysis of the AFL field umpire', Journal of Science and Medicine in Sport, vol. 3, no. 2, pp. 132-139.
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The purpose of the present study was to quantify the movement patterns and work intensities of field umpires while officiating in the three-umpire system of the Australian Football League (AFL). Five umpires were randomly selected and videoed throughout five AFL-matches played at the Brisbane Cricket Ground. Each video was analysed manually for time spent in each of four movement modalities: forward, backward, sideways and stationary which were further analysed into the categories of forward sprinting, forward cruising/jogging and forward walking; backward fast/moderate and backward slow: sideways movement and stationary. The following calculations were made: a) the total time spent performing each movement modality; b) the relative contribution (%) of time spent in each activity; and c) the work to rest ratio. The relative time contribution of each movement modality was: Sprinting (1.9±0.2%), Cruising/Jogging (26.1±3.2%), Walking (21.9±3.1%), Fast/Moderate Backward (14.6±1.2%), Slow Backward (13.6±1.0%), Sideways (2.2±0.3%) and Stationary (19.7±2.7%). The average time of effort for each movement modality were found to be: Sprinting (2.2±0.4 secs), Cruising/Jogging (6.09±1.3 secs), Walking (9.9±1.1 secs), Backward Fast/Moderate (4.4±0.3 secs), Backward Slow (5.2±0. 8 secs), Sideways (1.7±0.1 secs) and Stationary (7.4±1.4 secs). The average work to rest ratio was approximately between 1:4 - 1:5. The current findings provide a detailed description of the movement patterns and work intensities of AFL field umpires which may be used in the development of training programs specific to the three-umpire system.
De Abreu Lourenco, R 2000, 'Stated Preference Discrete Choice Modelling', CHERE Health Economics Review, no. 15.
Dr. Center, JR, Nguyen, TV, Sambrook, PN & Eisman, JA 2000, 'Hormonal and Biochemical Parameters and Osteoporotic Fractures in Elderly Men', Journal of Bone and Mineral Research, vol. 15, no. 7, pp. 1405-1411.
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Abstract Low testosterone has been associated with hip fracture in men in some studies. However, data on other hormonal parameters and fracture outcome in men is minimal. This study examined the association between free testosterone (free T) estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps strength, femoral neck bone mineral density (FN BMD), and fracture data (1989–1997) also were obtained. Fractures were classified as major (hip, pelvis, proximal tibia, multiple rib, vertebral, and proximal humerus) or minor (remaining distal upper and lower limb fractures). Fifty-four subjects had a fracture (24 major and 30 minor). There was no association between minor fractures and any hormonal parameter. Risk of major fracture was increased 2-fold for each SD increase in age, decrease in weight and height, and increase in SHBG, and risk of major fracture was increased 3-fold for each SD decrease in quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression). Independent predictors of major fracture were FN BMD, 2.7 (1.5–4.7; odds ratio [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5–5.3); and SHBG, 1.7 (1.2–2.4). An abnormal value for three factors resulted in a 30-fold increase in risk but only affected 2% of the population. It is not immediately apparent how 25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk. They may be markers for biological age or health status not measured by methods that are more traditional and as such may be useful in identifying those at high risk of fracture.
Dr. Nguyen, TV & Eisman, JA 2000, 'Genetics of Fracture: Challenges and Opportunities', Journal of Bone and Mineral Research, vol. 15, no. 7, pp. 1253-1256.
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Gabrys, B & Bargiela, A 2000, 'General fuzzy min-max neural network for clustering and classification', IEEE Transactions on Neural Networks, vol. 11, no. 3, pp. 769-783.
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Grbich, C, Parker, D & Maddocks, I 2000, 'Communication and Information Needs of Care-Givers of Adult Family Members at Diagnosis and during Treatment of Terminal Cancer', Progress in Palliative Care, vol. 8, no. 6, pp. 345-350.
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Heise, CE, O'Dowd, BF, Figueroa, DJ, Sawyer, N, Nguyen, T, Im, D-S, Stocco, R, Bellefeuille, JN, Abramovitz, M, Cheng, R, Williams, DL, Zeng, Z, Liu, Q, Ma, L, Clements, MK, Coulombe, N, Liu, Y, Austin, CP, George, SR, O'Neill, GP, Metters, KM, Lynch, KR & Evans, JF 2000, 'Characterization of the Human Cysteinyl Leukotriene 2 Receptor', Journal of Biological Chemistry, vol. 275, no. 39, pp. 30531-30536.
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The contractile and inflammatory actions of the cysteinyl leukotrienes (CysLTs), LTC4, LTD4, and LTE4, are thought to be mediated through at least two distinct but related CysLT G protein-coupled receptors. The human CysLT1 receptor has been recently cloned and characterized. We describe here the cloning and characterization of the second cysteinyl leukotriene receptor, CysLT2, a 346-amino acid protein with 38% amino acid identity to the CysLT1 receptor. The recombinant human CysLT2 receptor was expressed in Xenopus oocytes and HEK293T cells and shown to couple to elevation of intracellular calcium when activated by LTC4, LTD4, or LTE4. Analyses of radiolabeled LTD4 binding to the recombinant CysLT2 receptor demonstrated high affinity binding and a rank order of potency for competition of LTC4 = LTD4 >> LTE4. In contrast to the dual CysLT1/CysLT2 antagonist, BAY u9773, the CysLT1 receptor-selective antagonists MK-571, montelukast (Singulair(TM)), zafirlukast (Accolate(TM)), and pranlukast (Onon(TM)) exhibited low potency in competition for LTD4 binding and as antagonists of CysLT2 receptor signaling. CysLT2 receptor mRNA was detected in lung macrophages and airway smooth muscle, cardiac Purkinje cells, adrenal medulla cells, peripheral blood leukocytes, and brain, and the receptor gene was mapped to chromosome 13q14, a region linked to atopic asthma.
Hoang, DB & Wang, Z 2000, 'Performance of TCP applications over ATM networks with ABR and UBR services - a simulation analysis', COMPUTER COMMUNICATIONS, vol. 23, no. 9, pp. 802-815.
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This paper aims to present a comparative simulation study of the performance of TCP traffic over ATM networks with UBR and ABR services, to identify weaknesses of currently most promising ATM congestion control schemes; and to indicate the requirements f
Hoang, DB, Yu, X & Feng, D 2000, 'Fair intelligent bandwidth allocation for rate-adaptive video traffic', COMPUTER COMMUNICATIONS, vol. 23, no. 14-15, pp. 1425-1436.
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This paper presents an algorithm for network bandwidth sharing using explicit rate feedback, the Fair Intelligent Bandwidth Allocation (FIBA) for transporting rate-adaptive video traffic. We show that the FIBA algorithm is capable of allocating bandwidth
HUTVÁGNER, G, MLYNÁROVÁ, L & NAP, J-P 2000, 'Detailed characterization of the posttranscriptional gene-silencing-related small RNA in a GUS gene-silenced tobacco', RNA, vol. 6, no. 10, pp. 1445-1454.
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Posttranscriptional gene-silencing phenomena such as cosuppression and RNA interference are associated with the occurrence of small, about 21-23 nt short RNA species homologous to the silenced gene. We here show that the small RNA present in silenced transgenic plants can easily be detected in total RNA isolated according to standard procedures. This will allow for the development of routine and early screenings for the presence of small RNA species and, therefore, gene silencing in transgenic plants. We further demonstrate that the small RNA fraction can be visualized with the SYBR Green II RNA stain, isolated from a gel, labeled and used as a specific probe. Using these approaches, we have fine-mapped the sequences of the GUS gene that are represented in the small RNA fraction of a GUS-silenced tobacco line containing an inverted repeat of the GUS gene. In this tobacco line, the silencing-associated small RNA is a mixture of fragments that cover the 3' two-thirds of the GUS coding region. The 5' coding and the 3' noncoding ends of the GUS mRNA are not represented in the small RNA fraction. The RNA fragments are not likely to be a primary synthesis product of an RNA-dependent RNA polymerase, but rather degradation products from nuclease activity. Surprisingly, RNA isolated from wild-type, untransformed plants showed the presence of a similar-sized small RNA pool. This might indicate the existence of small RNA species from putative endogenous genes that are down regulated by a similar posttranscriptional gene-silencing mechanism. The possibility of isolating and labeling the small RNA pool from wild-type plants will provide a way to identify and study such putative genes.
Jones, G & Nguyen, TV 2000, 'Associations Between Maternal Peak Bone Mass and Bone Mass in Prepubertal Male and Female Children', Journal of Bone and Mineral Research, vol. 15, no. 10, pp. 1998-2004.
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Abstract The aim of this study was to estimate heritability of bone density in premenopausal women, prepubertal male, and prepubertal female child pairs. We studied 291 pairs (mothers, mean age, 33 years, range 22–45 years; children, mean age, 7.92 years, range 7.32-8.92 years). Bone density and body composition were assessed by dual-energy X-ray absorptiometry. Height and weight were measured in both mother and child. Body size-adjusted heritability estimates for areal bone density (g/cm2) were all statistically significant (femoral neck, 59%; lumbar spine, 38%; total body, 41%) and were consistently and significantly higher in mother-daughter pairs (n = 105) as compared with mother-son pairs (n = 186). Heritability estimates for bone mineral apparent density (BMAD; g/cm3) were marginally lower but remained statistically significant at all sites (femoral neck, 51%; lumbar spine, 32%; total body, 38%). Maternal osteopenia was associated with significant reductions in bone mass at all sites in the children (femoral neck, 0.75 SD and p < 0.0001; lumbar spine, 0.61 SD and p < 0.0001; total body, 0.43 SD and p = 0.012). Mother-child bone areal bone density correlation coefficients and prediction of low bone mass in the child were greater (but this did not reach statistical significance) if the corresponding anatomical site in the mother was used for prediction with the exception of the total body. These data confirm that heritability of bone mass extends to prepubertal children and is gender- and possibly site-specific as well as under separate genetic control to growth. Furthermore, the strength of the mother-child association is such that bone density screening of mothers would make it possible to identify most prepubertal children at higher risk of osteoporosis in later life.
Jones, PM & George, AM 2000, 'Symmetry and structure in P‐glycoprotein and ABC transporters', European Journal of Biochemistry, vol. 267, no. 17, pp. 5298-5305.
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The ABC superfamily of membrane transporters is one of the largest classes of proteins across all species and one of the most intensely researched. ABC proteins are involved in the trafficking of a diverse variety of biological molecules across cell membranes, with some members implicated in medical syndromes such as cystic fibrosis and multidrug resistance to anti‐cancer drugs. In the absence of X‐ray crystallographic data, structural information has come from spectroscopy, electron microscopy, secondary structure prediction algorithms and residue substitution, epitope labelling and cysteine cross‐linking studies. These have generally supported a model for the topology of the transmembrane domains of ABC transporters in which a single aqueous pore is formed by a toroidal ring of 12 α helices, deployed in two arcs of six helices each. Although this so‐called 6 + 6 helix model can be arranged in either mirror or rotational symmetry configurations, experimental data supports the former. In this review, we put forward arguments against both configurations of this 6 + 6 helix model, based on what is known generally about symmetry relationships in proteins. We relate these arguments to P‐glycoprotein, in particular, and discuss alternative models for the structure of ABC transporters in the light of the most recent research.
Kennerson, M, Nassif, N & Nicholson, G 2000, 'The CMT1A-REP Binary Repeat from Disease Causing Genomic Re-arrangements to a Role in Gene Evolution', Current Genomics, vol. 1, no. 1, pp. 81-90.
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Landers, P, Kerr, KG, Rowbotham, TJ, Tipper, JL, Keig, PM, Ingham, E & Denton, M 2000, 'Survival and Growth of Burkholderia cepacia Within the Free-Living Amoeba Acanthamoeba polyphaga', European Journal of Clinical Microbiology & Infectious Diseases, vol. 19, no. 2, pp. 121-123.
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Lee, DK, Cheng, R, Nguyen, T, Fan, T, Kariyawasam, AP, Liu, Y, Osmond, DH, George, SR & O'Dowd, BF 2000, 'Characterization of Apelin, the Ligand for the APJ Receptor', Journal of Neurochemistry, vol. 74, no. 1, pp. 34-41.
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Abstract: The apelin peptide was recently discovered and demonstrated to be the endogenous ligand for the G protein‐coupled receptor, APJ. A search of the GenBank databases retrieved a rat expressed sequence tag partially encoding the preproapelin sequence. The GenBank search also revealed a human sequence on chromosome Xq25‐26.1, containing the gene encoding preproapelin. We have used the rat sequence to screen a rat brain cDNA library to obtain a cDNA encoding the full‐length open reading frame of rat preproapelin. This cDNA encoded a protein of 77 amino acids, sharing an identity of 82% with human preproapelin. Northern and in situ hybridization analyses revealed both human and rat apelin and APJ to be expressed in the brain and periphery. Both sequence and mRNA expression distribution analyses revealed similarities between apelin and angiotensin II, suggesting they that share related physiological roles. A synthetic apelin peptide was injected intravenously into male Wistar rats, resulting in immediate lowering of both systolic and diastolic blood pressure, which persisted for several minutes. Intraperitoneal apelin injections induced an increase in drinking behavior within the first 30 min after injection, with a return to baseline within 1 h.
Lee, DK, Lynch, KR, Nguyen, T, Im, D-S, Cheng, R, Saldivia, VR, Liu, Y, Liu, ISC, Heng, HHQ, Seeman, P, George, SR, O’Dowd, BF & Marchese, A 2000, 'Cloning and characterization of additional members of the G protein-coupled receptor family', Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, vol. 1490, no. 3, pp. 311-323.
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A search of the expressed sequence tag (EST) database retrieved a human cDNA sequence which partially encoded a novel G protein-coupled receptor (GPCR) GPR26. A human genomic DNA fragment encoding a partial open reading frame (ORF) and a rat cDNA encoding the full length ORF of GPR26 were obtained by library screening. The rat GPR26 cDNA encoded a protein of 317 amino acids, most similar (albeit distantly related) to the serotonin 5- HT(5A) and gastrin releasing hormone BB2 receptors. GPR26 mRNA expression analysis revealed signals in the striatum, pons, cerebellum and cortex. HEK293 and Rh7777 cells transfected with GPR26 cDNA displayed high basal cAMP levels, slow growth rate of clonal populations and derangements of normal cell shape. We also used a sequence reported only in the patent literature encoding GPR57 (a.k.a. HNHCI32) to PCR amplify a DNA fragment which was used to screen a human genomic library. This resulted in the cloning of a genomic fragment containing a pseudogene, ψGPR57, with a 99.6% nucleotide identity to GPR57. Based on shared sequence identities, the receptor encoded by GPR57 was predicted to belong to a novel subfamily of GPCRs together with GPR58 (a.k.a. phBL5, reported only in the patent literature), putative neurotransmitter receptor (PNR) and a 5-HT4 pseudogene. Analysis of this subfamily revealed greatest identities (~56%) between the receptors encoded by GPR57 and GPR58, each with shared identities of ~40% with PNR. Furthermore, ψGPR57, GPR58, PNR and the 5-HT4 pseudogene were mapped in a cluster localized to chromosome 6q22-24. PNR and GPR58 were expressed in COS cells, however no specific binding was observed for various serotonin receptor-specific ligands. (C) 2000 Elsevier Science B.V.
Lee, S 2000, 'Oligomerization of Dopamine and Serotonin Receptors', Neuropsychopharmacology, vol. 23, no. 4, pp. S32-S40.
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Until recently, it has largely been assumed that G proteincoupled receptors (GPCRs) function as monomeric entities. However, over the past few years, we and others havedocumented that GPCRs can form dimers and oligomers, leading to a re-evaluation of the mechanisms thought tomediate GPCR function. Despite the growing number ofinvestigations into dimerization, little is known about thestructural basis of receptor-receptor interactions and thefunctional consequences of dimer formation. Here, wepresent a brief review of some insights we have gained intothe dimerization of dopamine and serotonin receptors. Wehave demonstrated that agonist-regulated trafficking isidentical for receptor monomers and dimers, however, agonist treatment appears to stabilise the receptor oligomers. An investigation of the structural assemblybetween receptors involved in dimerization showed thatthere are several sites of interaction including hydrophobictransmembrane domain interactions and intermoleculardisulphide bonds. We have also examined receptor hetero-oligomerization and demonstrated the potential for novelfunctions as a result of these associations. Finally, as aresult of these observations, we have been able to presentevidence that GPCRs function as oligomers in the cell. © 2000, American College of Neuropsychopharmacology.
Lee, SP, O'Dowd, BF, Ng, GYK, Varghese, G, Akil, H, Mansour, A, Nguyen, T & George, SR 2000, 'Inhibition of Cell Surface Expression by Mutant Receptors Demonstrates that D2 Dopamine Receptors Exist as Oligomers in the Cell', Molecular Pharmacology, vol. 58, no. 1, pp. 120-128.
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Numerous mutant G protein-coupled receptors with diminished or no function have been described that are naturally occurring or that are the product of gene manipulation. It has largely been assumed that receptor mutants do not affect the function of the wild-type receptor; however, the occurrence of G protein-coupled receptor dimerization suggests the possibility that an intermolecular interaction between mutant and wild-type receptors can occur. We have shown previously that the D2 dopamine receptor (D2DR) exists as dimers in cell lines and brain tissue. In this study, we demonstrated that mutant D2DR can modulate the function of the wild-type D2DR. While attempting to elucidate the structure of the D2DR dimer, we demonstrated that nonfunctional D2DR substitution and truncation mutants antagonized wild-type D2DR function. Furthermore, from analyses of this interaction between the receptor mutants and the D2DR, using photoaffinity labeling, we provide evidence that the D2DR is oligomeric in the cell.
Li, J, Dong, G & Ramamohanarao, K 2000, 'Making Use of the Most Expressive Jumping Emerging Patterns for Classification', Knowledge Discovery And Data Mining, Proceedings: Current Issues And New Applications, vol. 1805, no. NA, pp. 220-232.
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Classification aims to discover a model from training data that can be used to predict the class of test instances. In this paper, we propose the use of jumping emerging patterns (JEPs) as the basis for a new classifier called them JEP-Classifier. Each J
Lim, S, Roche, N, Oliver, BG, Mattos, W, Barnes, PJ & Chung, KF 2000, 'Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers - Regulation by interleukin-10', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 162, no. 4, pp. 1355-1360.
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Mcnie, CM, Barton, DC, Ingham, E, Tipper, JL, Fisher, J & Stone, MH 2000, 'The prediction of polyethylene wear rate and debris morphology produced by microscopic asperities on femoral heads', Journal of Materials Science: Materials in Medicine, vol. 11, no. 3, pp. 163-174.
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Melrose, J, Smith, S, Rodgers, K, Little, C, Burkhardt, D & Ghosh, P 2000, 'Immunolocalisation of BPTI-like serine proteinase inhibitory proteins in mast cells, chondrocytes and intervertebral disc fibrochondrocytes of ovine and bovine connective tissues. An immunohistochemical and biochemical study', Histochemistry and Cell Biology, vol. 114, no. 2, pp. 137-146.
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A polyclonal anti-bovine pancreatic trypsin inhibitor (BPTI) IgY was raised in chickens immunised with aprotinin The anti-BPTI IgY was subsequently isolated lated from egg yolks and purified to homogeneity by affinity chromatography on immobilised aproti
Miao, X & Ben-Nissan, B 2000, 'Microstructure and properties of zirconia-alumina nanolaminate sol-gel coatings', Journal of Materials Science, vol. 35, no. 2, pp. 497-502.
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Zirconia-alumina multilayer nanolaminate coatings were applied on stainless steel 316 substrates by a sol-gel dipping method. The coatings were characterized using X-ray diffraction, optical and scanning electron microscopy. The hardness and elastic modulus, the wear resistance and the oxidation resistance of the coatings were measured and assessed. It was observed that the coatings possessed fine grains, fine pores and high retention of tetragonal zirconia phase. The coatings exhibited high hardness and elastic modulus as well as good resistance to oxidation at high temperatures. However, these properties may be influenced by the interactions at the coating/substrate interface.
Moxham, L, Arnold, T, Coutts, A, Michaels, A & Ray, R 2000, 'Cardiovascular Disease in Regional Queensland: A Case Study Identifying the Implications for Changing the Primary Health Care Educational Paradigm', Australian Journal of Primary Health, vol. 6, no. 1, pp. 37-37.
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Australia is perceived by many as the 'lucky' country and the image that has been portrayed to the rest of the world is one that projects a nation of tanned, active, healthy, and sports-loving individuals. This image is outdated and instead Australia is a nation with a national health problem. The health problem is having an impact which is increasingly problematic for governments. It has long been recognised that primary prevention, can be developed in two ways: by using a whole of population approach or through selective targeting (Naidoo & Wills, 1998). Within this context, this paper has chosen to explore and discuss a selective targeting approach through a case analysis of cardiovascular disease in regional Australia. In Australia, cardiovascular disease continues to be one of the major causes of death. This fact is a matter of great concern to all Australians but is particularly significant for people living in the regional city of Rockhampton, Central Queensland, where the death rate from cardiovascular disease is significantly higher than it is for the rest of the state of Queensland (354.4 deaths per 100,000 people per year compared with 310.6, Harper & Taylor, 1997, p. 21). The high death rate from heart disease in Queensland is even higher than the Australian average (Harper & Taylor, 1997, p. 22). Research previously conducted has revealed certain trends regarding cardiovascular disease. This research extends the available knowledge by measuring the cost in economic terms to the community. The findings explain the implications for Rockhampton employers and places regional health professionals in a better position to develop further research as well as to implement and explain alternative health strategies.
Nguyen, HB, Rivers, EP, Havstad, S, Knoblich, B, Ressler, JA, Muzzin, AM & Tomlanovich, MC 2000, 'Critical Care in the Emergency Department A Physiologic Assessment and Outcome Evaluation', Academic Emergency Medicine, vol. 7, no. 12, pp. 1354-1361.
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Abstract. Objectives: The changing landscape of health care in this country has seen an increase in the delivery of care to critically ill patients in the emergency department (ED). However, methodologies to assess care and outcomes similar to those used in the intensive care unit (ICU) are currently lacking in this setting. This study examined the impact of ED intervention on morbidity and mortality using the Acute Physiology and Chronic Health Evaluation (APACHE II), the Simplified Acute Physiology Score (SAPS II), and the Multiple Organ Dysfunction Score (MODS). Methods: This was a prospective, observational cohort study over a three‐month period. Critically ill adult patients presenting to a large urban ED and requiring ICU admission were enrolled. APACHE II, SAPS II, and MODS scores and predicted mortality were obtained at ED admission, ED discharge, and 24, 48, and 72 hours in the ICU. In‐hospital mortality was recorded. Results: Eighty‐one patients aged 64 ± 18 years were enrolled during the study period, with a 30.9% in‐hospital mortality. The ED length of stay was 5.9 ± 2.7 hours and the hospital length of stay was 12.2 ± 16.6 days. Nine (11.1%) patients initially accepted for ICU admission were later admitted to the general ward after ED intervention. Septic shock was the predominant admitting diagnosis. At ED admission, there was a significantly higher APACHE II score in nonsurvivors (23.0 ± 6.0) vs survivors (19.8 ± 6.5, p = 0.04), while there was no significant difference in SAPS II or MODS scores. The APACHE II, SAPS II, and MODS scores were significantly lower in survivors than nonsurvivors throughout the hospital stay (p ≤ 0.001). The hourly rates of change (decreases) in APACHE II, SAPS II, and MODS scores were significantly greater during the ED stay (‐0.55 ± 0.64, ‐1.02 ± 1.10, and ‐0.16 ± 0.43, respectively) than subsequent periods o...
Nguyen, TV & Eisman, JA 2000, 'Assessment of Significant Change in BMD: A New Approach', Journal of Bone and Mineral Research, vol. 15, no. 2, pp. 369-370.
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Nguyen, TV, Blangero, J & Eisman, JA 2000, 'Genetic Epidemiological Approaches to the Search for Osteoporosis Genes', Journal of Bone and Mineral Research, vol. 15, no. 3, pp. 392-401.
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Abstract Important progress has been made in the identification of specific environmental factors and estimation of hereditary components in bone density, quantitative ultrasound (QUS), and bone turnover indices. By contrast, the search for specific genes that regulate bone mass has progressed rather slowly, and the results are more difficult to interpret and reproduce. This article reviews the genetics of osteoporosis and problems plaguing genetic research. It is argued that the search for genes involved in the expression of osteoporotic phenotypes should be based on linkage studies in relatively homogeneous populations. Strategies for increasing the power of studies, such as making use of information from extended pedigrees and multivariate analysis, are discussed. With the advent of a comprehensive human genetic linkage map, a complete identification of genes for osteoporosis appears feasible. Understanding the genetic mechanisms and their interactions with environmental factors should allow more focused and cost-effective osteoporosis prevention and treatment strategies.
Nguyen, TV, Center, JR & Eisman, JA 2000, 'Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study', Maturitas, vol. 36, no. 1, pp. 27-34.
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Nguyen, TV, Pocock, NA & Eisman, JA 2000, 'Interpretation of Bone Mineral Density Measurement and Its Change', Journal of Clinical Densitometry, vol. 3, no. 2, pp. 107-119.
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O'Brien, BA, Harmon, BV, Cameron, DP & Allan, DJ 2000, 'Nicotinamide prevents the development of diabetes in the cyclophosphamide-induced NOD mouse model by reducing beta-cell apoptosis', The Journal of Pathology, vol. 191, no. 1, pp. 86-92.
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The development of diabetes in non-obese diabetic (NOD) mice, which normally takes between 3 and 7 months, can be accelerated by cyclophosphamide (CY) injections, with rapid progression to diabetes within only 2±3 weeks. This insulin-dependent diabetes mellitus (IDDM) can be prevented or delayed in CY-treated NOD mice by nicotinamide (NA). The present study was undertaken to determine the mode of cell death responsible for the development of IDDM in CYtreated male NOD mice and to investigate the effect of NA on beta-cell death. Apoptotic beta cells were present within the islets of Langerhans in haematoxylin and eosin-stained sections of the pancreata harvested from 3- and 12-week-old male NOD mice, from 8 h until 14 days after a single intraperitoneal injection of CY (150 mg/kg body weight). The maximum amount of betacell apoptosis in 3-week-old animals occurred 1±2 days after CY treatment (20 apoptotic cells per 100 islets), after which time levels of apoptosis declined steadily throughout the 14-day period studied. The incidence of beta-cell apoptosis in 12-week-old male NOD mice occurred in two peaks; the ®rst was recorded 8±24 h after CY treatment (30 apoptotic cells/100 islets), while the second, at 7 days (36 apoptotic cells per 100 islets), coincided with increased insulitis. Administration of NA 15 min before CY treatment, and thereafter daily, substantially reduced the amount of apoptosis and effectively eliminated (4 apoptotic cells per 100 islets) the second wave of beta-cell apoptosis seen at day 7 in 12-week-old animals given CY alone. These results show that apoptosis is the mode of beta-cell death responsible for the development of CY-induced IDDM and that prevention of IDDM by NA is associated with a reduction in beta-cell apoptosis.
O'Dowd, BF, Lee, DK, Huang, W, Nguyen, T, Cheng, R, Liu, Y, Wang, B, Gershengorn, MC & George, SR 2000, 'TRH-R2 exhibits similar binding and acute signaling but distinct regulation and anatomic distribution compared with TRH-R1.', Mol Endocrinol, vol. 14, no. 1, pp. 183-193.
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TRH (thyroliberin) is a tripeptide (pGlu-His-ProNH2) that signals via G protein-coupled receptors. Until recently, only a single receptor for TRH was known (TRH-R1), but two groups identified a second receptor, TRH-R2. We independently discovered TRH-R2. Using an extensive set of TRH analogs, we found no differences in TRH-R1 and TRH-R2 binding or in acute stimulation of signaling. TRH-R2 was more rapidly internalized upon binding TRH and exhibited a greater level of TRH-induced down-regulation than TRH-R1. During prolonged exposure to TRH, cells expressing TRH-R2 exhibited a lower level of gene induction than cells expressing TRH-R1. TRH-R2 receptor mRNA was present in very discrete nuclei and regions of rat brain. A major mRNA transcript for TRH-R2 was seen in the cerebral cortex, pons, thalamus, hypothalamus, and midbrain with faint bands found in the striatum and pituitary. The extensive distribution of TRH-R2 in the brain suggests that it mediates many of the known functions of TRH that are not transduced by TRH-R1. The variations in agonist-induced internalization and down-regulation/desensitization, and anatomic distribution of TRH-R2 compared with TRH-R1, suggest important functional differences between the two receptors.
Parker, D & De Bellis, A 2000, 'A profile of dying residents in South Australian nursing homes', Nursing and Residential Care, vol. 2, no. 2, pp. 66-72.
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In Australia there is increasing interest in palliative care for nursing home residents who experience a period of increased care need in the months, weeks or days before death (Maddocks et al, 1996). The term ‘palliative care’ has been used interchangeably with ‘hospice care’ and ‘terminal care’ in Australia. In this article, however, palliative care refers to a holistic philosophy of care relating to the care needs of those in the terminal phase of illness. This article focuses on residents identified as dying and requiring palliative care in 10 South Australian nursing homes.
Patiag, D, Qu, X, Gray, S, Idris, I, Wilkes, M, Seale, JP & Donnelly, R 2000, 'Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro', Journal of Endocrinology, vol. 167, no. 3, pp. 525-531.
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Angiotensin II (ANGII) increases insulin sensitivity in diabetic and non-diabetic subjects, even at subpressor doses, and because there is 'crosstalk' between ANGII and insulin-signaling pathways the underlying mechanism may not be due solely to changes in regional blood flow. A series of experimental studies was undertaken to evaluate the effects of ANGII on glucose and lipid metabolism in vivo and in vitro. Groups of fructose-fed, insulin-resistant Sprague-Dawley (SD) rats were pre-treated with 0.3 mg/kg per day of the AT(1)-receptor antagonist L-158 809 (n=16), or vehicle (n=16), by oral gavage. This was prior to an oral glucose tolerance test (day 5) and measurement of the effects of ANGII infusion (20 ng/kg per min i.v. for 3 h) on whole-body insulin sensitivity using the insulin suppression test (day 7). The effect of ANGII infusion on total triglyceride secretion rate (TGSR) was evaluated in normal SD rats pretreated for 7 days with L-158 809 (n=12) or vehicle (n=12). AT(1)- and AT(2)- receptor mRNA expression and [(3)H]2-deoxyglucose uptake were assessed in cultured L6 myoblasts. Short-term treatment with L-158 809 had no effect on glucose tolerance or fasting triglyceride levels in fructose-fed rats. ANGII infusion had no effect on insulin sensitivity in fructose-fed rats pretreated with vehicle (steady-state plasma glucose (SSPG) values 8.1+/-1.6 vs 8. 4+/-0.4 mmol/l), but pretreatment with L-158 809 resulted in ANGII having a modest insulin antagonist effect in this insulin-resistant model (SSPG values 9.6+/-0.3 vs 7.1+/-0.6, P<0.03). ANGII infusion had no significant effect on TGSR (e.g. 24.6+/-1.4 vs 28.4+/-0.9 mg/100 g per h in vehicle-treated animals). RT-PCR analysis showed that L6 cells express both AT(1)- and AT(2)-receptor mRNA. Incubation with ANGII (10(-9) and 10(-8) M) had no significant effect on the dose-response curve for insulin-stimulated [(3)H]2-deoxyglucose uptake. For example, C(I200) values (dose of insulin requ...
Randell, AG, Nguyen, TV, Bhalerao, N, Silverman, SL, Sambrook, PN & Eisman, JA 2000, 'Deterioration in Quality of Life Following Hip Fracture: A Prospective Study', Osteoporosis International, vol. 11, no. 5, pp. 460-466.
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Rodgers, KJ & Dean, RT 2000, 'Metabolism of protein-bound DOPA in mammals', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 32, no. 9, pp. 945-955.
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Protein-bound 3,4-dihydroxyphenylalanine (DOPA) can be generated in mammalian cells by both controlled enzymatic pathways, and by uncontrolled radical reactions. Protein-bound DOPA (PB-DOPA) has reducing activity and the capacity to inflict secondary dam
Tasevski, V, Benn, D, King, M, Luttrell, B & Simpson, A 2000, 'Mitogenic Effect of Lithium in FRTL-5 Cells Can be Reversed by BlockingDe NovoCholesterol Synthesis and Subsequent Signal Transduction', Thyroid, vol. 10, no. 4, pp. 305-311.
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Lithium therapy is the therapeutic mainstay for bipolar disorder and has been associated in the thyroid with euthymic goiter, hyper and hypothyroidism as well as thyroid autoimmune disease. The FRTL-5 cell line is a well known model of thyroid cell physiology, where lithium has been shown to increase 3H-thymidine uptake at concentrations of 2 mM. This mitogenic effect was not associated with adenylate cyclase as measured by cyclic adenosine monophosphate (cAMP) production. The de novo synthesis of cholesterol is an important signal transduction pathway in FRTL-5 cells, where newly synthesized Rho GTPase is geranylgeranylated, enabling membrane localization of the G-protein and subsequent G1 to S-phase transition, resulting from extracellular stimulation. Here we confirm lithium mitogenicity at therapeutically relevant concentrations (1 mM) and demonstrate a lithium-associated accumulation of FRTL-5 cells in S-phase of the cell cycle. These effects could be abolished by Pravastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), the rate-limiting enzyme in the formation of intermediates (de novo cholesterol synthesis) required for G-protein prenylation. Pravastatin, similar to lithium, showed no effect on cAMP production either under basal or thyroid stimulating hormone (TSH)-stimulated conditions indicating that de novo cholesterol synthesis is not involved with adenylate cyclase. The inhibitory effect of pravastatin could be overcome by reinitiating de novo cholesterol synthesis. This was achieved by the addition of the cell permeable, first metabolite (mevalonate) after HMG-CoA, which allowed the cycle to continue, leading eventually to protein prenylation, despite the presence of Pravastatin. These novel findings demonstrate lithium involvement in de novo cholesterol synthesis and G-protein prenylation, an important signal transduction pathway in FRTL-5 cells.
Thompson, MD, Gonzalez, N, Nguyen, T, Comings, DE, George, SR & O'Dowd, BF 2000, 'Serotonin transporter gene polymorphisms in alcohol dependence', Alcohol, vol. 22, no. 2, pp. 61-67.
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The serotonin transporter (5-HTT) gene is a candidate gene in alcohol dependence because serotonin reuptake inhibitors (SRIs) can alleviate alcohol withdrawal. Studies of the 5-HTT gene in alcohol dependence have not resulted in a consensus. Recent studies have examined the transcriptionally active promoter polymorphism, a 44-bp deletion resulting in short (S) or long (L) alleles. In this study, 131 alcohol-dependent patients of Northern and Western European descent were genotyped. Seventy of these patients were diagnosed with alcohol dependence without comorbid disorders. Sixty-one patients were diagnosed with alcohol dependence comorbid with Tourette syndrome (alcoholic-TS). We found an excess of the S allele in alcohol-dependent patients (47%) compared with 125 ethnically matched controls (39%). A similar trend was found in 150 ethnically matched TS patients without alcohol dependence comorbidity (51%). However, the statistical significance of this trend in the data was not present after Bonferroni correction. The data presented suggests a trend toward increased frequency of the S promoter allele in alcohol-dependent, alcoholic-TS and TS patients. (C) 2000 Elsevier Science Inc.
Tie, H, Walker, BD, Singleton, C, Bursill, J, Wyse, KR, Valenzuela, S, Qiu, M, Breit, SN & Campbell, TJ 2000, 'The Antipsychotic Agents Thioridazine, Chlorpromazine And Clozapine Block The Human-ether-a-go-go-related Gene (herg) Potassium Channel: Cellular Mechanism For Proarrhythmia', Journal Of The American College Of Cardiology, vol. 35, no. 2, pp. 1-1.
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NA
Tipper, JL, Ingham, E, Hailey, JL, Besong, AA, Fisher, J, Wroblewski, BM & Stone, MH 2000, 'Quantitative analysis of polyethylene wear debris, wear rate and head damage in retrieved Charnley hip prostheses', Journal of Materials Science: Materials in Medicine, vol. 11, no. 2, pp. 117-124.
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Submicrometer- and micrometer-sized ultra-high molecular weight polyethylene (UHMWPE) wear particles have been associated with osteolysis and failure of total artificial joints. Previous studies have isolated predominantly submicrometer-sized particles at the expense of larger particles ( > 10 μm). This study aimed to isolate and characterize quantitatively all sizes of UHMWPE wear particles generated in 18 Charnley hip prostheses. In addition, to analyze the wear debris with respect to the total volumetric wear of the cup and damage to the femoral head. Particle size distributions ranged from 0.1 to - > 1000 μm. A significant proportion (3-82%) of the mass of the wear debris isolated was > 10 μm. The mode of the frequency distribution of the particles was in the range 0.1-0.5 μm for all patients. However, analysis of the mass of wear debris as a function of its size allowed differentiation of the wear debris from different patients. Femoral head damage was associated with high volumetric wear and increased numbers of biologically active submicrometer-sized particles. (C) 2000 Kluwer Academic Publishers.
Tuch, BE, Yao, M, Tabiin, MT, Simpson, AM, Gross, DJ, Holman, S, Humphrey, R & Szymanska, B 2000, 'Reversal Of Diabetes By Transplantation Of Insulin-producing Human Liver Cells', Diabetologia, vol. 43, no. 0, pp. 1-1.
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NA
Valenzuela, SM, Mazzanti, M, Tonini, R, Qiu, MR, Warton, K, Musgrove, EA, Campbell, TJ & Breit, SN 2000, 'The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle', The Journal of Physiology, vol. 529, no. 3, pp. 541-552.
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1. NCC27 is a nuclear chloride ion channel, identified in the PMA-activated U937 human monocyte cell line. NCC27 mRNA is expressed in virtually all cells and tissues and the gene encoding NCC27 is also highly conserved. Because of these factors, we have
Waite, PME, Gorrie, CA, Benetatos, E, Brown, J, Duflou, J & Gibson, T 2000, 'Neuropathology in children following fatal road trauma', EUROPEAN JOURNAL OF NEUROSCIENCE, vol. 12, pp. 223-223.
Watterson, PA 2000, 'Energy calculation of a permanent magnet system by surface and flux integrals (the flux-mmf method)', IEEE Transactions on Magnetics, vol. 36, no. 2, pp. 470-475.
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Watterson, PA, Woodard, JC, Ramsden, VS & Reizes, JA 2000, 'VentrAssist hydrodynamically suspended, open, centrifugal blood pump', ARTIFICIAL ORGANS, vol. 24, no. 6, pp. 475-477.
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