bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical experience with metal-on-metal total joint replacements: Indications and results
Authors: Learmonth I D , Gheduzzi S , Vail T P 
Published: October 2007

Survivorship of total joint arthroplasty depends on the durability of fixation and durability of articulation. The metal-on-polyethylene articular couple has been the most widely used. Polyethylene wear (and the associated cytochemical events that culminate in osteolysis) has been identified as a major factor adversely influencing the durability of joint replacement. This stimulated the orthopaedic community to explore the possibility of using alternative bearings with lower wear rates. Hard-on-hard bearings have been shown to be associated with reduced wear. Metal-on-metal bearings have wear rates that are 20-100 times lower than metal on conventional polyethylene. However, patients with metal-on-metal articulations have increased levels of cobalt and chromium in the serum and urine, and this has raised concerns about toxicity, mutagenesis, and hypersensitivity. At this stage there is no epidemiological evidence to suggest that the risk of carcinogenesis is anything more than theoretical. Successful long-term results have been reported with the cast cobalt-chromium metal-on-metal couples of the mid-1960s. Tissues retrieved at revision of these implants did not show the giant-cell inflammatory response associated with polyethylene particles. Several researchers have reported excellent mid-term results with the current generation of high-precision metal-on-metal bearings.
Development rationale for an articular surface replacement: A science-based evolution
Authors: Isaac G H , Siebel T , Schmalzried T P , Cobb A G , O'Sullivan T , Oakeshott R D , Flett M , Vail T P 
Published: October 2007

Hip resurfacing has an enduring appeal because of the advantages of bone conservation and maximal joint stability. However, a far from satisfactory experience with earlier resurfacing designs led to its virtual disappearance in the 1980s. The concept was reintroduced in the late 1990s. The current generation of resurfacing devices generally consisted of a large-diameter metal-on-metal articulation, the femoral components being cemented and the acetabular components utilizing various forms of cementless fixation. The encouraging medium-term results, with a follow-up of up to 8 years using the current generation of surface replacement joints, combined with favourable reports related to long-term performance of some metal bearings have led to a rapid increase in the use of such components with these devices. This trend is most marked in younger, more active patients who have expectations of restoration of lifestyle in addition to improved mobility and pain relief and in whom failure with conventional total hip replacement is much higher than previously reported with more sedentary patients. The aim of this paper is, firstly, to highlight a number of areas of improvement and, secondly, to explain how these may be addressed by making modifications to the design of both implants and instrumentation and to the surgical technique. The areas identified for improvement were tissue preservation (thinner components, and reduced steps between sizes), acetabular cup issues (fixation, insertion, and positioning), femoral component issues (design, loading, and cementation), improved bearing surface characteristics, and simplified precise instrumentation with a low-trauma surgical technique.
Cementing techniques in hip resurfacing
Authors: Chandler M , Z Kowalski R S , Watkins N D , Briscoe A , R New A M 
Published: October 2007

The subject of the cementing technique in hip resurfacing has been poorly studied to date. The hip resurfacing prosthesis is unique in the family of cemented prostheses because the cement mantle is blind (hidden underneath the implant) and is radiographically obscured. This presents an immediate challenge to the surgeon at the time of surgery, but also has a longer-term implication in terms of lack of post-operative clinical observation. This should be compared with total hip replacement or total knee replacement where the cement mantle can at least be partially observed both intra- and post-operatively. With this in mind, the objective of this review is, firstly, to understand the cement mantles typically achieved in current clinical practice and, secondly, to identify those factors affecting the cement mantle and to consolidate them into an improved and reproducible cementing technique. The outcome of this work shows that the low-viscosity technique can commonly lead to excessive cement penetration in the proximal femoral head and an incompletely seated component, whereas a more consistent controlled cement mantle can be achieved with a high-viscosity cementing technique. Consequently, it is recommended that a high-viscosity technique should be used to minimize the build-up of excessive cement, to reduce the temperature created by the exothermic polymerization, and to help to ensure correct seating of the prosthesis. A combination of these factors is potentially critical to the clinical success of some articular surface replacement (ASR) procedures. It is important to note that we specifically studied the DePuy ASR system; therefore only the general principles (and not the specifics) of the cementing technique may apply to other resurfacing prostheses, because of differences in internal geometry, clearance, and surgical technique.
The tribology of metal-on-metal total hip replacements
Authors: Scholes S C , Unsworth A 
Published: October 2007

Total hip surgery is an effective way of alleviating the pain and discomfort caused by diseased or damaged joints. However, in the majority of cases, these joints have a finite life. The main reason for failure is osteolysis (bone resorption). It is well documented that an important cause of osteolysis, and therefore the subsequent loosening and failure of conventional metal- or ceramic-on-ultra-high molecular weight polyethylene joints, is the body's immunological response to the polyethylene wear particles. To avoid this, interest has been renewed in metal-on-metal joints. The intention of this paper is to review the studies that have taken place within different laboratories to determine the tribological performance of new-generation metal-on-metal total hip replacements. These types of joint offer a potential solution to enhance the longevity of prosthetic hip systems; however, problems may arise owing to the effects of metal ion release, which are, as yet, not fully understood.
Adaptive control of dynamically substructured systems: The single-input single-output case
Authors: Stoten D P , Hyde R. A. 
Published: October 2007

In recent years, there has been much interest in using the principle of dynamic substructuring as a framework for the testing of critical engineering components and systems. The most significant advantage of the method is that it can offer the opportunity to test full-size non-linear components within a laboratory environment. Such a test would be run in parallel with a real-time numerical simulation of the remaining part of the overall system to be emulated. Potentially, the most significant disadvantage of the method is the very high fidelity of control that is required, in order to achieve near-perfect synchronization of the test rig and the numerical model. This problem is further exacerbated by the presence of unknown and changing dynamic parameters, disturbances, and non-linearities in the test rig. The purpose of this paper is to lay a foundation for the linear control of dynamically sub-structured systems and, leading on from that, robust adaptive control via an extension to the adaptive minimal control synthesis (MCS) algorithm. Comparative simulation results from using the linear and adaptive control strategies are also included in the paper.
Change in the Governance of Medicine: the politics of self-regulation
Authors: Salter Brian 
Published: October 2007

English
This article develops and applies an analytical framework which shows how the political forces at work in the triangular relationship between medicine, society and the State interact to guide and constrain change in medicine’s system of governance. Under pressure from society and the State, the medical profession is now obliged to reform itself and accept a higher degree of public accountability. This article explores the dimensions of the changes required, their likely impact on the political benefits which historically have sustained the triangular relationship, and hence the complex politics which must inevitably accompany such reforms.
The Development of Domiciliary Care: mission accomplished?
Authors: Wistow Gerold , Hardy Brian 
Published: October 2007

English
The development of domiciliary care through the independent sector was central to the successful implementation of the 1993 community care changes. A considerable degree of success has been achieved: there has been substantial growth in the volume of home care hours funded by local authorities, all of it concentrated in the independent sector. As a result, the sector now provides more than two fifths of all local authority-funded home care. This pattern of development has not been unproblematic, however. Purchaser–provider relationships have created some provider instability and threatened continuity of care for users. The continuing task for local authorities as purchasers is to develop relationships with their providers which ensure that the quality of care services, and the way they are delivered, are consistent with user-defined standards.
Staff Qualifications and Ratios in Children’s Homes: are they the key to the outcomes of care?
Authors: Sinclair Ian , Gibbs Ian 
Published: October 2007

English
Official reports into methods of improving the performance of children’s homes have focused on staff training, staff ratios and size. This article tests these conclusions on 48 children’s homes. It develops a measure of performance based on the social climate of a home and relates this to size, to the proportion of qualified staff, to whether the head of home was qualified and to staff ratios. The analysis supports the importance of size but finds no relationship between staff ratios and qualifications on the one hand and performance on the other.
Mass Spectrometry–Based Detection of Hemoglobin E Mutation by Allele-Specific Base Extension Reaction
Authors: Tsang Jason CH , Charoenkwan Pimlak , Chow Katherine CK , Jin Yongjie , Wanapirak Chanane , Sanguansermsri Torpong , Lo YM Dennis , Chiu Rossa WK 
Published: October 2007

Abstract
Background: The specific detection of a minor population of mutant DNA molecules requires methods of high specificity and sensitivity. While the single-allele base extension reaction (SABER) was shown to be useful for the detection of certain beta-thalassemia mutations, we encountered problems with false positivity during development of SABER for the noninvasive prenatal diagnosis of the hemoglobin E (HbE) disease. Systematic optimization resulted in an alternative protocol, the allele-specific base extension reaction (ASBER).
Methods: An artificial model was established by mixing genomic DNA of HbE carriers and normal individuals. Effects of terminator concentration and annealing temperature on the nonspecificity of SABER were then studied. The use of a single relevant terminator and the other 3 types of dideoxynucleotide as competing terminators were also compared in the development of the ASBER protocol. Thirteen cases of HbE-susceptible pregnancies were tested to compare the SABER and the ASBER protocols.
Results: Decreasing the single relevant terminator concentration and increasing the annealing temperature in SABER were found to improve specificity. The use of the other 3 types of dideoxynucleotide as competing terminators was shown to offer better detection sensitivity than a single terminator in ASBER. Genotyping results were all correctly determined by ASBER, except one false-negative detection (sensitivity: 80%, specificity: 100%).
Conclusions: An alternative mass spectrometry–based protocol for noninvasive prenatal diagnosis, ASBER, has been successfully developed to allow the detection of a minor DNA population with a point mutation.
Glucocorticoid receptor-mediated expression of kallikrein 10 in human breast cancer cell lines
Authors: Kulasingam Vathany , Diamandis Eleftherios P. 
Published: October 2007

Abstract
Using the breast cell lines MCF-10A, MDA-MB-468 and T-47D, we investigated the role of various glucocorticoids in regulating human kallikrein 10 expression. We found that increased concentrations of glucocorticoids decreased KLK10 expression in MCF-10A and increased KLK10 expression in MDA-MB-468 and T-47D cells. Stimulation of the cell lines using other steroid hormones did not yield any difference in KLK10 expression in MCF-10A and MDA-MB-468 cells, suggesting that regulation of KLK10 occurs primarily through glucocorticoids. However, T-47D cells expressed higher levels of KLK10 upon dihydrotestosterone stimulation. Blocking the glucocorticoid receptor (GR) demonstrated that the mechanisms of induction and repression are different in the three cell lines studied. Taken together, our results suggest an alternative mode of KLK10 regulation – by glucocorticoids via GR-dependent mechanisms.
Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3
Authors: Schmutzler Cornelia , Mentrup Birgit , Schomburg Lutz , Hoang-Vu Cuong , Herzog Volker , Köhrle Josef 
Published: October 2007

Abstract
The thyroid gland has an exceptionally high selenium content, even during selenium deficiency. At least 11 selenoproteins are expressed, which may be involved in the protection of the gland against the high amounts of H2O2 produced during thyroid hormone biosynthesis. As determined here by in situ hybridization and Northern blotting experiments, glutathione peroxidases (GPx) 1 and 4 and selenoprotein P were moderately expressed, occurring selectively in the follicular cells and in leukocytes of germinal follicles of thyroids affected by Hashimoto's thyroiditis. Selenoprotein 15 was only marginally expressed and distributed over all cell types. GPx3 mRNA was exclusively localized to the thyrocytes, showed the highest expression levels and was down-regulated in 5 of 6 thyroid cancer samples as compared to matched normal controls. GPx3 could be extracted from thyroidal colloid by incubation with 0.5% sodium dodecyl sulfate indicating that this enzyme is (i) secreted into the follicular lumen and (ii) loosely attached to the colloidal thyroglobulin. These findings are consistent with a role of selenoproteins in the protection of the thyroid from possible damage by H2O2. Particularly, GPx3 might use excess H2O2 and catalyze the polymerization of thyroglobulin to the highly cross-linked storage form present in the colloid.
Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function
Authors: Savaskan Nicolai E. , Ufer Christoph , Kühn Hartmut , Borchert Astrid 
Published: October 2007

Abstract
Selenoproteins have been recognized as modulators of brain function and signaling. Phospholipid hydroperoxide glutathione peroxidase (GPx4/PHGPx) is a unique member of the selenium-dependent glutathione peroxidases in mammals with a pivotal role in brain development and function. GPx4 exists as a cytosolic, mitochondrial, and nuclear isoform derived from a single gene. In mice, the GPx4 gene is located on chromosome 10 in close proximity to a functional retrotransposome that is expressed under the control of captured regulatory elements. Elucidation of crystallographic data uncovered structural peculiarities of GPx4 that provide the molecular basis for its unique enzymatic properties and substrate specificity. Monomeric GPx4 is multifunctional: it acts as a reducing enzyme of peroxidized phospholipids and thiols and as a structural protein. Transcriptional regulation of the different GPx4 isoforms requires several isoform-specific cis-regulatory sequences and trans-activating factors. Cytosolic and mitochondrial GPx4 are the major isoforms exclusively expressed by neurons in the developing brain. In stark contrast, following brain trauma, GPx4 is specifically upregulated in non-neuronal cells, i.e., reactive astrocytes. Molecular approaches to genetic modification in mice have revealed an essential and isoform-specific function for GPx4 in development and disease. Here we review recent findings on GPx4 with emphasis on its molecular structure and function and consider potential mechanisms that underlie neural development and neuropathological conditions.
An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors
Authors: Wildemann Dirk , Hernandez Alvarez Birte , Stoller Gerlind , Zhou Xiao Zhen , Lu Kun Ping , Erdmann Frank , Ferrari David , Fischer Gunter 
Published: October 2007

Abstract
The peptidyl prolyl cis/trans isomerase (PPIase) Pin1 plays an important role in phosphorylation-dependent events of the cell cycle. This function is linked to its display of two phosphothreonine/phosphoserine-proline binding motifs, one within the type IV WW domain and a second within the parvulin-like catalytic domain. By microinjection of the compound Ac-Phe-D-Thr(PO3H2)-Pip-Nal-Gln-NH2, which inhibits Xenopus laevis Pin1 with a K
i value of 19.4±1.5 nM, into the animal pole of X. laevis embryos at the two-cell stage, the impact of Pin1 PPIase activity on cell cycle progression and embryonic development could be analysed, independent of WW domain-mediated phosphoprotein binding. Injected embryos showed a dramatically decreased survival rate at late stages of development that could only be partially compensated by co-injection with mRNAs of enzymatically active Pin1 variants, demonstrating that the phosphorylation-specific PPIase activity of Pin1 is essential for cell division and development in X. laevis.
Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals
Authors: Conrad Marcus , Schneider Manuela , Seiler Alexander , Bornkamm Georg W. 
Published: October 2007

Abstract
The redox enzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) has emerged as one of the most significant selenoenzymes in mammals, corroborated by early embryonic lethality of PHGPx null mice. PHGPx is one of five selenium-dependent glutathione peroxidases and the second glutathione peroxidase to be discovered in 1982. PHGPx has a particular position within this family owing to its peculiar structural and catalytic properties, its multifaceted roles during male gametogenesis, and its necessity for early mouse development. Interestingly, mice devoid of endogenous glutathione die at the same embryonic stage as PHGPx-deficient mice compatible with the hypothesis that a similar phenotype of embryonic lethality may be provoked by PHGPx deficiency and lack of its reducing substrate glutathione. Various gain- and loss-of-function approaches in mice have provided some insights into the physiological functions of PHGPx. These include a protective role for PHGPx in response to irradiation, increased resistance of transgenic PHGPx mice to toxin-induced liver damage, a putative role in various steps of embryogenesis, and a contribution to sperm chromatin condensation. The expression of three forms of PHGPx and early embryonic lethality call for more specific studies, such as tissue-specific disruption of PHGPx, to precisely understand the contribution of PHGPx to mammalian physiology and under pathological conditions.
B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance
Authors: Geisberger Roland , Kiermayer Claudia , Hömig Cornelia , Conrad Marcus , Schmidt Jörg , Zimber-Strobl Ursula , Brielmeier Markus 
Published: October 2007

AbstractThioredoxin reductases (Txnrds) are a group of selenoenzymes participating in cellular redox regulation. Three Txnrd isoforms are known, each of which exhibits distinct cellular localisation and tissue-specific expression pattern. Txnrd1 is found in the cytoplasm, expression of Txnrd2 is restricted to mitochondria and Txnrd3 shows testis-specific expression. Recently, it was shown that Txnrd2 strongly affects the development of blood cells, since mouse embryos deficient forTxnrd2are severely anaemic, show increased apoptosis in foetal liver and possess haematopoietic liver stem cells of reduced capacity to proliferatein vitro. However, becauseTxnrd2-deficient mice die at embryonic day 13.5, it was not known how this enzyme affects blood cell function in the adult animal. In the present study we show that conditionalTxnrd2knockouts generated using CD4-and CD19Cre transgenic mice lack Txnrd2 expression in CD4-- and CD19-positive T- and B-lymphocytes, respectively. However, the development and differentiation of both cell types in thymus and bone marrow was not significantly impaired. In addition, B-cell proliferation and activation in response to CD40 and IL-4 was unaltered inTxnrd2-deficient B-cells.
Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
Authors: Hu Ying , Urig Sabine , Koncarevic Sasa , Wu Xinjiang , Fischer Marina , Rahlfs Stefan , Mersch-Sundermann Volker , Becker Katja 
Published: October 2007

Abstract
We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks. Isothiocyanates inhibited isolated redox-active enzymes in a time- and dose-dependent manner. As shown for the most active compound, benzyl isothiocyanate (BITC), on thioredoxin reductase, the inhibition has an initial competitive part (K
i=6.1±1.0 μM) followed by a time-dependent irreversible inhibition (k
2=72.8±25.5 M
-1 s-1). Also, glutathione reductase and glutathione S-transferase were irreversibly modified by BITC. Sulforaphane led to irreversible inhibition of the studied redox enzymes, but with 5–10 times lower k
2 values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k
2=100 M
-2 s-1). This reaction might contribute to enhanced oxidative stress and the induction of the selenoprotein glutathione peroxidase as determined on activity and transcript levels. All chemopreventive agents tested induced transcript levels of genes associated with cell cycle arrest and apoptosis. This upregulation was accompanied by a dose-dependent decrease in cell number. Our data indicate that modulation of cellular redox networks is likely to contribute to the effects of sulfur-containing chemopreventive agents.
Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells
Authors: Steinbrenner Holger , Alili Lirija , Stuhlmann Dominik , Sies Helmut , Brenneisen Peter 
Published: October 2007

Abstract
Selenoprotein P (SeP) is a highly glycosylated plasma protein containing up to 10 selenocysteine residues. It is secreted by hepatocytes and also by the human hepatoma cell line HepG2. Pharmacological inhibitors interfering with N-glycosylation, intracellular trafficking and calcium homeostasis were applied to examine post-translational processing and secretion of SeP by HepG2 cells. In parallel, the prototypic secretory glycoprotein α1-antitrypsin was used as technical control. Secretion of SeP was stimulated by increasing the extracellular calcium concentration and by inhibiting the release of sequestered calcium through dantrolene or U-73122. In contrast, brefeldin A and thapsigargin suppressed SeP secretion. Tunicamycin and monensin induced the synthesis of truncated non-glycosylated and partially glycosylated forms of SeP, which were secreted in spite of their impaired glycosylation. Both non-glycosylated and partially glycosylated SeP is utilised as selenium donor by target cells: impaired glycosylation affected neither the ability of SeP to induce the synthesis of the selenoenzyme cytosolic glutathione peroxidase nor its capacity to protect endothelial cells from oxidative stress.