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Setor K. Kunutsor Michael R. Whitehouse Ashley W. Blom Tim Board Peter Kay B. Mike Wroblewski Valérie Zeller Szu-Yuan Chen Pang-Hsin Hsieh Bassam A. Masri Amir Herman Jean-Yves Jenny Ran Schwarzkopf John-Paul Whittaker Ben Burston Ronald Huang Camilo Restrepo Javad Parvizi Sergio Rudelli Emerson Honda David E. Uip Guillem Bori Ernesto Muñoz-Mahamud Elizabeth Darley Alba Ribera Elena Cañas Javier Cabo José Cordero-Ampuero Maria Luisa Sorlí Redó Simon Strange Erik Lenguerrand Rachael Gooberman-Hill Jason Webb Alasdair MacGowan Paul Dieppe Matthew Wilson Andrew D. Beswick The Global Infection Orthopaedic Management Collaboration 《European journal of epidemiology》2018,33(10):933-946
One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6–20.7) and 32.3 (95% CI 27.3–38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58–5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip. 相似文献
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Alasdair John Edgar 《Journal of muscle research and cell motility》1989,10(6):465-472
Summary The Ca2+-dependent actin-polymerization nucleating protein of the cytoplasmic fraction of Baby hamster kidney (BHK) C13 cells has been isolated by anion-exchange, hydroxyapatite and gel-filtration chromatography. This protein has been identified as a cytoplasmic gelsolin by the following criteria: molecular mass of 90 kDa on SDS-PAGE, immunocrossreactivity with pig plasma gelsolin and similar actin-binding properties to gelsolins purified from other sources. BHK gelsolin forms a 12 ternary complex with rabbit muscle actin that is dependent on the presence of Ca2+. The ternary complex is dissociated on chelation of Ca2+ with EGTA to a binary complex and free actin. BHK gelsolin nucleates the polymerization of pyrene-labelled G-actin in a Ca2+-dependent manner. The proportion of unpolymerized monomer is increased in the presence of BHK gelsolin by an amount consistent with capping of the positive filament ends. The rate of actin depolymerization induced by diluting F-actin to below its critical concentration (Cc) is unaffected by the presence of BHK gelsolin in EGTA. However, in the presence of Ca2+ the rate of depolymerization is increased indicating that BHK gelsolin severs actin filaments in a Ca2+-dependent manner. 相似文献
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David D. Kim Donna J. Lang Darren E. R. Warburton Melissa L. Woodward Randall F. White Alasdair M. Barr William G. Honer Ric M. Procyshyn 《Clinical autonomic research》2017,27(6):407-410
Purpose
To explore the relationship between antipsychotic-associated antagonism of alpha2-adrenergic receptors and resting heart rate in individuals with schizophrenia.Methods
Thirty-one inpatients treated with antipsychotics were included in this exploratory analysis. Antipsychotic doses were converted to haloperidol equivalents for alpha2-adrenergic receptor antagonism. Resting heart rate was measured with the patient in the seated upright posture.Results
After controlling for confounding variables, the relationship between alpha2-adrenergic receptor antagonism and resting heart rate demonstrated a positive linear effect (P = 0.002) as well as a nonlinear effect that accounted for an additional 14% of the variability in resting heart rate (P = 0.005).Conclusion
The observed inverted-U relationship between alpha2-adrenergic receptor antagonism and resting heart rate can possibly be attributed to an altered response of beta1-adrenergic receptors to increased norepinephrine release. Further investigations are required to confirm this exploratory finding, taking into account additional variables that include other receptors which either directly or indirectly influence heart rate.ClinicalTrials.gov Identifier
NCT01392885.48.
Human Mast Cell Apoptosis Is Regulated Through Bcl-2 and Bcl-XL 总被引:4,自引:0,他引:4
Mekori YA Gilfillan AM Akin C Hartmann K Metcalfe DD 《Journal of clinical immunology》2001,21(3):171-174
It is well established that human mast cell proliferation and maturation are regulated by kit ligand (stem cell factor). Little is known, however, about how these two processes are negatively regulated and thus, how mast cell number is controlled in normal and pathologic conditions. We therefore first hypothesized that SCF-dependent human mast cells would undergo programmed cell death (apoptosis) on removal of SCF as has been shown for growth factor-dependent rodent mast cells. We then examined whether SCF acts as a survival factor through the regulation of the bcl-2 family of apoptosis-regulatory genes. As hypothesized, elimination of SCF from primary peripheral blood-derived human mast cell cultures resulted in a significant apoptotic process. During apoptosis, down-regulation of the two apoptosis-regulatory proteins Bcl-2 and Bcl-XLwas observed. Moreover, a deregulated expression of these two proteins was found in two human mast cell lines which are SCF-independent. Thus, SCF functions as a survival factor by repressing apoptosis of human mast cells through Bcl-2 and Bcl-XL. Deregulated expression of these antiapoptotic proteins may contribute to proliferation and accumulation of mast cells in certain forms of systemic mast cell disorders. 相似文献
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Spindle-shaped viruses are a dominant morphotype in hypersaline waters but their molecular characteristics and their relationship to other archaeal viruses have not been determined. Here, we describe the isolation, characteristics and genome sequence of His2, a spindle-shaped halovirus, and compare it to the previously reported halovirus His1. Their particle dimensions, host-ranges and buoyant densities were found to be similar but they differed in their stabilities to raised temperature, low salinity and chloroform. The genomes of both viruses were linear dsDNA, of similar size (His1, 14,464 bp; His2, 16,067 bp) and mol% G+C (approximately 40%), with long, inverted terminal repeat sequences. The genomic termini of both viruses are likely to possess bound proteins. They shared little nucleotide similarity and, except for their putative DNA polymerase ORFs, no significant similarity at the predicted protein level. A few of the 35 predicted ORFs of both viruses showed significant matches to sequences in GenBank, and these were always to proteins of haloarchaea. Their DNA polymerases showed 42% aa identity, and belonged to the type B group of replicases that use protein-priming. Purified His2 particles were composed of four main proteins (62, 36, 28 and 21 kDa) and the gene for the major capsid protein was identified. Hypothetical proteins similar to His2 VP1 are present in four haloarchaeal genomes but are not part of complete prophages. This, and other evidence, suggests a high frequency of recombination between haloviruses and their hosts. His1 and His2 are unlike fuselloviruses and have been placed in a new virus group, Salterprovirus. 相似文献
50.
Joanne L. Jones Chia-Ling Phuah Amanda L. Cox Sara A. Thompson Maria Ban Jacqueline Shawcross Amie Walton Stephen J. Sawcer Alastair Compston Alasdair J. Coles 《The Journal of clinical investigation》2009,119(7):2052-2061
Phase II clinical trials revealed that the lymphocyte-depleting humanized monoclonal antibody alemtuzumab (Campath-1H) is highly effective in the treatment of early relapsing-remitting multiple sclerosis. However, 30% of patients develop autoimmunity months to years after pulsed exposure to alemtuzumab, usually targeting the thyroid gland and, more rarely, blood components. In this study, we show that autoimmunity arose in those patients with greater T cell apoptosis and cell cycling in response to alemtuzumab-induced lymphocyte depletion, a phenomenon that is driven by higher levels of IL-21. Before treatment, patients who went on to develop secondary autoimmunity had more than 2-fold greater levels of serum IL-21 than the nonautoimmune group. We suggest that serum IL-21 may, therefore, serve as a biomarker for the risk of developing autoimmunity months to years after alemtuzumab treatment. This has implications for counseling those patients with multiple sclerosis who are considering lymphocyte-depleting therapy with alemtuzumab. Finally, we demonstrate through genotyping that IL-21 expression is genetically predetermined. We propose that, by driving cycles of T cell expansion and apoptosis to excess, IL-21 increases the stochastic opportunities for T cells to encounter self antigen and, hence, for autoimmunity. 相似文献