Bell, J, Tipper, JL, Ingham, E, Stone, MH, Wroblewski, BM & Fisher, J 2002, 'Quantitative analysis of UHMWPE wear debris isolated from the periprosthetic femoral tissues from a series of Charnley total hip arthroplasties.', Biomed Mater Eng, vol. 12, no. 2, pp. 189-201.
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Submicrometer and micrometer-sized UHMWPE wear particles have been associated with osteolysis and failure of total hip replacements. A previous study by Tipper et al. examined the wear debris isolated from the acetabular periprosthetic tissues from 18 Charnley total hip replacements, and compared this data to the tribological variables of the prostheses. The present study aimed to isolate the UHMWPE wear debris from the femoral periprosthetic tissues from 10 of the same cohort of patients, and compare it with the debris isolated from the corresponding acetabular tissues. A variety of particle morphologies were observed, discrete submicrometer particles, along with flakes and fibrils. The particle size distributions ranged from 0.1 to >250 microm, however, the largest particles were only found in samples when the femoral head damage was characterised as low (R(pm) < 0.2 microm). The mode of the frequency distribution of particles was in the range of 0.1-0.5 microm for all the femoral tissues. Considerable variations were found in the mass distributions of the wear particles as a function of size for different patients. The net mass of debris isolated from the femoral tissues was significantly lower (p < 0.05, Student's t-test) than from the corresponding acetabular tissues. This along with considerable spatial variation in the net mass of debris isolated from the different regions of the same sample of acetabular tissue, indicates that the transportation of the debris has a marked effect on the net mass of debris accumulated in different tissues.
Buist, MD 2002, 'Effects of a medical emergency team on reduction of incidence of and mortality from unexpected cardiac arrests in hospital: preliminary study', BMJ, vol. 324, no. 7334, pp. 387-390.
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Fisher, J, Hu, XQ, Tipper, JL, Stewart, TD, Williams, S, Stone, MH, Davies, C, Hatto, P, Bolton, J, Riley, M, Hardaker, C, Isaac, GH, Berry, G & Ingham, E 2002, 'An in vitro study of the reduction in wear of metal-on-metal hip prostheses using surface-engineered femoral heads', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 216, no. 4, pp. 219-230.
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Although the wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/106 cycles) is much lower than the more widely used polyethylene-on-metal bearings, there are concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically, in the human body. The aim of this study was to investigate the possibility of reducing the volume of wear, the concentration of metal debris and the level of metal ion release through using surfaceengineered femoral heads. Three thick (8-12 μm) coatings (TiN, CrN and CrCN) and one thin (2 μm) coating (diamond-like carbon, DLC), were evaluated on the femoral heads when articulating against high carbon content cobalt-chromium alloy acetabular inserts (HC CoCrMo) and compared with a clinically used MOM cobalt-chromium alloy bearing couple using a physiological anatomical hip joint simulator (Leeds Mark II). This study showed that CrN, CrCN and DLC coatings produced substantially lower wear volumes for both the coated femoral heads and the HC CoCrMo inserts. The TiN coating itself had little wear, but it caused relatively high wear of the HC CoCrMo inserts compared with the other coatings. The majority of the wear debris for all half-coated couples comprised small, 30 nm or less, CoCrMo metal particles. The Co, Cr and Mo ion concentrations released from the bearing couples of CrN-, CrCN- and DLC-coated heads articulating against HC CoCrMo inserts were at least 7 times lower than those released from the clinical MOM prostheses. These surface-engineered femoral heads articulating on HC CoCrMo acetabular inserts produced significantly lower wear volumes and rates, and hence lower volumetric concentrations of wear particles, compared with the clinical MOM prosthesis. The substantially lower ion concentration released by these surface-engineered components provides important evidence to support the clinical application of this technology.
Hutvagner, G & Zamore, PD 2002, 'RNA interference: Nature hates double strands', BIOFUTUR, vol. 228, no. 228, pp. 52-57.
Hutvágner, G & Zamore, PD 2002, 'A microRNA in a Multiple-Turnover RNAi Enzyme Complex', Science, vol. 297, no. 5589, pp. 2056-2060.
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In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let - 7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Human let - 7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let - 7 –containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.
Hutvágner, G & Zamore, PD 2002, 'RNAi: nature abhors a double-strand', Current Opinion in Genetics & Development, vol. 12, no. 2, pp. 225-232.
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In organisms as diverse as nematodes, trypanosomes, plants, and fungi, double-stranded RNA triggers the destruction of homologous mRNAs, a phenomenon known as RNA interference. RNA interference begins with the transformation of the double-stranded RNA into small RNAs that then guide a protein nuclease to destroy their mRNA targets.
Ingram, J, Matthews, JB, Tipper, J, Stone, M, Fisher, J & Ingham, E 2002, 'Comparison of the biological activity of grade GUR 1120 and GUR 415HP UHMWPE wear debris.', Biomed Mater Eng, vol. 12, no. 2, pp. 177-188.
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This study evaluated the in vitro response of murine macrophages to clinically relevant polyethylene particles from two grades of UHMWPE at varying volume doses. Clinically relevant UHMWPE wear debris was generated in vitro using a tri-pin-on-disc tribometer. The debris was observed using a scanning electron microscope and analysed by image analysis. There was no significant difference in the wear rates of the two grades of UHMWPE. Analysis of the wear debris showed that GUR 415HP produced a higher percentage of mass of debris in the submeter size range compared to GUR 1120. The wear debris was co-cultured with C3H murine peritoneal macrophages at particle volume (microm(3)): cell number ratios of 100 :1, 50 :1, 10 :1 and 1 :1 for both grades of UHMWPE and additionally at 0.5 :1 and 0.1 :1 for grade GUR 415HP. The secretion of TNF-alpha was determined by ELISA. Significantly elevated levels of TNF-alpha were secreted at 100 :1 ratio when macrophages were challenged with wear debris from GUR 1120 and at 10 :1 and 1 :1 for debris from GUR 415HP. The results suggested that the greater percentage mass of debris in the submicrometer size range from GUR 415HP lead to a substantial increase in biological activity for this grade of UHMWPE on a volume for volume basis when compared with GUR 1120.
Molloy, D, Kaloo, PD, Cooper, M & Nguyen, TV 2002, 'Laparoscopic entry: a literature review and analysis of techniques and complications of primary port entry', Australian and New Zealand Journal of Obstetrics and Gynaecology, vol. 42, no. 3, pp. 246-254.
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ABSTRACTObjectiveTo obtain consensus as to the optimal form of entry technique for access to the peritoneal cavity.DesignA meta‐analysis of all relevant English language studies of laparoscopic entry complications.Main outcome measuresIncidence of bowel and major vascular injuries.ResultsBowel injuries occur in 0.7/1000 and major vascular injuries in 0.4/1000. The overall incidence of major injuries at time of entry is 1.1/1000. The direct entry technique is associated with a significantly reduced major injury incidence of 0.5/1000, when compared to both open and Veress entry produces (1.1 and 0.9/1000 respectively, p = 0.0005). Entry‐related bowel injuries are reported more often following general surgical laparoscopies than with gynaecological procedures (p = 0.001). No such difference is seen in the incidence of vascular injuries (p = 0.987). Open entry is statistically more likely to be associated with bowel injury than either Veress needle or direct entry. However, open entry appears to minimize vascular injury at time of entry.ConclusionsThere remains no clear evidence as to the optimal form of laparoscopic entry in the low‐risk patient. However, direct entry may be an under‐utilised and safe alternative to the Veress needle and open entry technique.
Naganathan, V, Macgregor, A, Snieder, H, Nguyen, T, Spector, T & Sambrook, P 2002, 'Gender Differences in the Genetic Factors Responsible for Variation in Bone Density and Ultrasound', Journal of Bone and Mineral Research, vol. 17, no. 4, pp. 725-733.
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Abstract Although genetic factors are thought to explain a large proportion of the variation in bone density in women, few studies have been conducted in men. Therefore, it is unclear whether the individual differences in bone strength between men and women are a reflection of gender differences in the relative influence of genetic and environmental factors on bone density variance. The aim of this study was to determine if there were gender differences in the genetic components of variance for bone density and ultrasound. In addition, the study aimed to explore the hypothesis that there are unique gender-specific genetic determinants of these traits. Bone mineral density (BMD) of the hip, distal forearm, and lumbar spine were measured by dual-energy X-ray absorptiometry (DXA) as well as quantitative ultrasound (QUS) at the calcaneus in healthy female twin pairs (286 identical [MZ] and 265 nonidentical [DZ]), male twin pairs (72 MZ and 65 DZ), and 82 opposite-sex (OS) pairs aged between 18 and 80 years. For hip BMD, distal forearm, and QUS measurements, the differences between MZ correlations and like-sex DZ correlations were similar for both sexes, suggesting little difference in the component of total variance explained by genetic factors between male and female twin pairs. However, correlations between OS twin pairs were lower than that of like-sex twin pairs, suggesting the possibility of unique gender-specific genetic effects. At the forearm, model fitting suggested a small gender difference in the magnitude of genetic variance as well as the presence of a unique gender-specific genetic variance component. Hip, lumbar spine, and QUS measurements were better explained by models that assumed no gender differences in genetic variance between the sexes, but the study had insufficient power to detect small differences in the genetic components of variance. The results of this study suggest that the proport...
Phung, H, Bauman, A, Nguyen, TV, Young, L, Tran, M & Hillman, K 2002, 'Risk factors for low birth weight in a socio-economically disadvantaged population: Parity, marital status, ethnicity and cigarette smoking', European Journal of Epidemiology, vol. 18, no. 3, pp. 235-243.
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Qin, C, Nguyen, T, Stewart, J, Samudio, I, Burghardt, R & Safe, S 2002, 'Estrogen Up-Regulation of p53 Gene Expression in MCF-7 Breast Cancer Cells Is Mediated by Calmodulin Kinase IV-Dependent Activation of a Nuclear Factor κB/CCAAT-Binding Transcription Factor-1 Complex', Molecular Endocrinology, vol. 16, no. 8, pp. 1793-1809.
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Schwarz, DS, Hutvágner, G, Haley, B & Zamore, PD 2002, 'Evidence that siRNAs Function as Guides, Not Primers, in the Drosophila and Human RNAi Pathways', Molecular Cell, vol. 10, no. 3, pp. 537-548.
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In Drosophila, two features of small interfering RNA (siRNA) structure - 5′ phosphates and 3′ hydroxyls - are reported to be essential for RNA interference (RNAi). Here, we show that as in Drosophila, a 5′ phosphate is required for siRNA function in human HeLa cells. In contrast, we find no evidence in flies or humans for a role in RNAi for the siRNA 3′ hydroxyl group. Our in vitro data suggest that in both flies and mammals, each siRNA guides endonucleolytic cleavage of the target RNA at a single site. We conclude that the underlying mechanism of RNAi is conserved between flies and mammals and that RNA-dependent RNA polymerases are not required for RNAi in these organisms.
Smith, GB 2002, 'Medical emergency teams and cardiac arrests in hospital', BMJ, vol. 324, no. 7347, pp. 1215a-1215.
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Tipper, JL, Hatton, A, Nevelos, JE, Ingham, E, Doyle, C, Streicher, R, Nevelos, AB & Fisher, J 2002, 'Alumina–alumina artificial hip joints. Part II: Characterisation of the wear debris from in vitro hip joint simulations', Biomaterials, vol. 23, no. 16, pp. 3441-3448.
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Törjék, O, Kiss, E, Mázikné Tokei, K, Hutvágner, G, Silhavy, D, Bánfalvi, Z, Kertész, Z, Pauk, J & Heszky, L 2002, 'Molecular homogeneity of conventional and doubled haploid wheat cultivars and their DH lines', Novenytermeles, vol. 51, no. 1, pp. 7-20.
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A traditional cultivar (GK Góbé), a cultivar of doubled haploid (DH) origin (GK Délibáb), various DH lines of GK Góbé (first cycle DH lines) and DH lines of GK Délibáb (second cycle DH lines) were compared with PCR-bascd molecular techniques. High molecular weight DNA was isolated from randomly selected individuals of these groups and analysed by the RAPD, SSR, STS and AFLP methods. The objective of the analyses was to determine the existence or magnitude of the difference between cultivars produced by classical and haploid methods (populations are represented by the individuals of each group), and to find which marker system would be most suitable to investigate the homogeneity of DH populations. From the 30 RAPD primers tested, only 6 differentiated the two cultivars (GK Góbé and Délibáb). Individual polymorphism could not be observed. There were 8 fragments generated on 15 loci with 12 SSR and STS primers, which were suitable to differentiate the two cultivars. Individual polymorphisms could be detected within the cultivar GK Délibáb (cultivar of doubled haploid origin) with primer WMS186. In the AFLP analyses, 7 of 8 primer combinations were suitable to show differences, resulting in an average of 100-150 fragments. Eighty-one polymorphic fragments were obtained with these 7 primer combinations. Twenty-three of the 81 polymorphic bands (markers) could detect individual differences. Nine of them were suitable to distingiushc cultivar GK Góbé and its DH group. Based on AFLP fragments, the fewest individual polymorphisms were obtained within the DH group of GK Délibáb (second cycle DH lines). The genetic stability of doubled haploid lines of androgenic origin is the prerequisite of their breeding value. The productivity and adaptability of the new DH varieties were similar to the conventional cultivars in field trials. In the present investigation conventional and DH varieties were analysed and compared by different molecular (RAPD, SSR, STS and AFL) m...
White, SA, Nguyen, T & Fernald, RD 2002, 'Social regulation of gonadotropin-releasing hormone', Journal of Experimental Biology, vol. 205, no. 17, pp. 2567-2581.
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Behavioral interactions among social animals can regulate both reproductive behavior and fertility. A prime example of socially regulated reproduction occurs in the cichlid fish Haplochromis burtoni, in which interactions between males dynamically regulate gonadal function throughout life. This plasticity is mediated by the brain, where neurons that contain the key reproductive regulatory peptide gonadotropin-releasing hormone (GnRH) change size reversibly depending on male social status. To understand how behavior controls the brain, we manipulated the social system of these fish, quantified their behavior and then assessed neural and physiological changes in the reproductive and stress axes. GnRH gene expression was assessed using molecular probes specific for the three GnRH forms in the brain of H. burtoni. We found that perception of social opportunity to increase status by a male leads to heightened aggressiveness, to increased expression of only one of the three GnRH forms and to increases in size of GnRH-containing neurons and of the gonads. The biological changes characteristic of social ascent happen faster than changes following social descent. Interestingly, behavioral changes show the reverse pattern: aggressive behaviors emerge more slowly in ascending animals than they disappear in descending animals. Although the gonads and GnRH neurons undergo similar changes in female H. burtoni, regulation occurs via endogenous rather than exogenous social signals. Our data show that recognition of social signals by males alters stress levels, which may contribute to the alteration in GnRH gene expression in particular neurons essential for the animal to perform in its new social status.
Endo, M, Tipper, JL, Barton, DC, Stone, MH, Ingham, E & Fisher, J 1970, 'Comparison of wear, wear debris and functional biological activity of moderately crosslinked and non-crosslinked polyethylenes in hip prostheses', Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, SAGE Publications, pp. 111-122.
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The wear, wear debris and functional biological activity of non-crosslinked and moderately crosslinked ultrahigh molecular weight polyethylene (UHMWPE) acetabular cups have been compared when articulating against smooth and intentionally scratched femoral heads. Volumetric wear rates were determined in a hip joint simulator and the debris was isolated from the lubricant and characterized by the percentage number and volumetric concentration as a function of particle size. The volumetric concentration was integrated with the biological activity function determined from in vitro cell culture studies to predict an index of specific biological activity (SBA). The product of specific biological activity and volumetric wear rate was used to determine the index of functional biological activity (FBA).On smooth femoral heads the crosslinked UHMWPE had a 30 per cent lower wear rate, but it had a greater percentage volume of smaller, more biologically active particles, which resulted in a similar index of FBA compared with the non-crosslinked material. On the scratched femoral heads the volumetric wear rate was three times higher for the moderately crosslinked UHMWPE and two times higher for the non-crosslinked UHMWPE compared with the smooth femoral heads. This resulted in a higher wear rate for the moderately crosslinked material on the scratched femoral heads. All the differences in wear rate were statistically significant. There were only small differences in particle volume concentration distributions, and this resulted in similar indices of FBA which were approximately twice the values of those found on the smooth femoral heads. Both materials showed lower wear and FBA than for previously studied aged and oxidized UHMWPE gamma irradiated in air. However, this study did not reveal any advantage in terms of predicted FBA for moderately crosslinked UHMWPE compared with non-crosslinked UHMWPE.
Jin, ZM, Medley, JB, Dowson, D, Hooke, CJ, Smith, SL, Booker, JF, Ikeuchi, K, Morita, Y, Nakat, K, Kim, YH, Sekino, T, Niihara, K, Spencer, N, Paré, P, Sawae, Y, Murakami, T, Sawano, T, Noda, I, Shimotoso, T, Chan, FW, Young, S, Stewart, TD, Williams, S, Tipper, JL, Ingham, E, Stone, MH & Fisher, J 1970, 'Session VII bio-tribology (1) - Hip and knee joints', Tribology Series, pp. 874-879.