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101.
Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: A systematic reappraisal of classic cytogenetic data
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Panagiotis Baliakas Michalis Iskas Anne Gardiner Zadie Davis Karla Plevova Florence Nguyen‐Khac Jitka Malcikova Achilles Anagnostopoulos Sharron Glide Sarah Mould Kristina Stepanovska Martin Brejcha Chrysoula Belessi Frederic Davi Sarka Pospisilova Anastasia Athanasiadou Kostas Stamatopoulos David Oscier 《American journal of hematology》2014,89(3):249-255
The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry ≥1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC (≥3 aberrations) was detected in 157 cases and significantly (P < 0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time‐to‐first‐treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior. Am. J. Hematol. 89:249–255, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
102.
Charlotte Bradbury Kate Fletcher Yongzhong Sun Carl Heneghan Chris Gardiner Andrea Roalfe Pollyanna Hardy Debbie McCahon Gail Heritage Helen Shackleford FD Richard Hobbs David Fitzmaurice 《British journal of haematology》2020,188(6):962-975
Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81–11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients. 相似文献
103.
Philip G. Drennan Evan J. Begg Sharon J. Gardiner Carl M.J. Kirkpatrick Steve T. Chambers 《International journal of antimicrobial agents》2019,53(4):401-407
We have evaluated the literature to review optimal dosing and monitoring of intravenous vancomycin in adults, in response to evolving understanding of targets associated with efficacy and toxicity. The area under the total concentration–time curve (0–24 h) divided by the minimum inhibitory concentration (AUC24/MIC) is the most commonly accepted index to guide vancomycin dosing for the treatment of Staphylococcus aureus infections, with a value of 400 h a widely recommended target for efficacy. Upper limits of AUC24 exposure of around 700 (mg/L).h have been proposed, based on the hypothesis that higher exposures of vancomycin are associated with an unacceptable risk of nephrotoxicity. If AUC24/MIC targets are used, sources of variability in the assessment of both AUC24 and MIC need to be considered. Current consensus guidelines recommend measuring trough vancomycin concentrations during intermittent dosing as a surrogate for the AUC24. Trough concentrations are a misleading surrogate for AUC24 and a poor end-point in themselves. AUC24 estimation using log-linear pharmacokinetic methods based on two plasma concentrations, or Bayesian methods are superior. Alternatively, a single concentration measured during continuous infusion allows simple AUC24 estimation and dose-adjustment. All of these methods have logistical challenges which must be overcome if they are to be adopted successfully. 相似文献
104.
Brenda J. Meyer John M. Gardiner Dermot M. Bowler 《Journal of autism and developmental disorders》2014,44(10):2514-2524
Rehearsal strategies of adults with autism spectrum disorders (ASDs) and demographically matched typically developed (TD) adults were strategically manipulated by cueing participants to either learn, or forget each list word prior to a recognition task. Participants were also asked to distinguish between autonoetic and noetic states of awareness using the Remember/Know paradigm. The ASD group recognised a similar number of to-be-forgotten words as the TD group, but significantly fewer to-be-learned words. This deficit was only evident in Remember responses that reflect autonoetic awareness, or episodic memory, and not Know responses. These findings support the elaborative encoding deficit hypothesis and provide a link between the previously established mild episodic memory impairments in adults with high functioning autism and the encoding strategies employed. 相似文献
105.
Maria H. Morrison Ciara Keane Louise M. Quinn Aoife Kelly Cliona O’Farrelly Colm Bergin Clair M. Gardiner 《Human immunology》2014
The interferon-lambda (IFNL) cytokines have been shown to be important in HCV infection with SNPs in the IFNL3 gene associated with both natural and treatment induced viral clearance. We have recently shown that rs1299860 (an IFNL3 associated SNP) and an NK cell gene, KIR2DS3, synergised to increase the odds of chronic infection in a homogenous cohort of Irish women infected with HCV. To characterise a biological basis for the genetic synergy, we investigated for any evidence that IFNL cytokines regulate NK cell functions. Using a range of functional responses, we did not find any evidence of NK cell activation by IFNL3, IFNL1 or IFNL2 cytokines. Similar results were found using human and murine NK cells. In addition, and in contrast to our preliminary study, we did not find any evidence that IFNL cytokines inhibited NK cell cytokine production; thus, the biological basis for the genetic synergy remains to be discovered. 相似文献
106.
Spread of X inactivation on chromosome 15 is associated with a more severe phenotype in a girl with an unbalanced t(X; 15) translocation
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107.
108.
Pierre H. Mangin Elizabeth E. Gardiner Warwick S. Nesbitt Steven W. Kerrigan Netanel Korin Wilbur A. Lam Mikhail A. Panteleev 《Journal of thrombosis and haemostasis》2020,18(3):748-752
Experimental videomicroscopic in vitro assays of thrombus formation based on blood perfusion are instrumental in a wide range of basic studies in thrombosis, screening for hereditary or acquired plateletrelated pathologies, and assessing the effectiveness of novel anti‐platelet therapies. Here, we discuss application of the broadly used “in vitro thrombosis model”: a frequently used assay to study the formation of 3D aggregates under flow, which involves perfusing anticoagulated whole blood over fibrillar collagen in a flow geometry of rectangular cross‐section, such as glass microcapillaries or parallel‐plate flow chambers. Major advantaged of this assay are simplicity and ability to reproduce the four main stages of platelet thrombus formation, i.e. platelet tethering, adhesion, activation and aggregation under a wide range of hemodynamic conditions. On the other hand, these devices represent, at best, simple reductive models of thrombosis. We also describe how blood flow assays can be used to study various aspects of platelet function on adhesive proteins and discuss the relevance of such flow models. Finally, we propose recommendations for standardization related to the use of this assay that cover collagen source, coating methods, micropatterning, sample composition, anticoagulation, choice of flow device, hemodynamic conditions, quantification challenges, variability, pre‐analytical conditions and other issues. 相似文献
109.
Arianne C Lim Kitty WM Bloemenkamp Kees Boer Johannes J Duvekot Jan Jaap HM Erwich Tom HM Hasaart Pieter Hummel Ben WJ Mol Jos PM Offermans Charlotte M van Oirschot Job G Santema Hubertina CJ Scheepers Willem A Schöls Frank PHA Vandenbussche Maurice GAJ Wouters Hein W Bruinse 《BMC pregnancy and childbirth》2007,7(1):1-6
Background
Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.Methods
552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.Results
The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.Conclusion
Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy. 相似文献110.
Irma E. Jrvel Hannah M. Mitchison David F. Callen Terry J. Lerner Norman A. Doggett Peter E. M. Taschner R. Mark Gardiner Sara E. Mole 《American journal of medical genetics. Part A》1995,57(2):316-319
CLN3 has been mapped genetically to 16p12, to the interval between D16S288 and D16S383, a sex-averaged genetic distance of 2.1 cM. Analysis of disease haplotypes for four microsatellite markers in this interval, D16S288, D16S299, D16S298, and SPN, has shown significant allelic association between one allele at each of these loci and CLN3. All four of the associated markers were used as nucleation sites in the isolation of genomic clones (YACs). A contig was assembled which contains 3 of the 4 associated markers and which confirmed the relative order of these markers. Marker D16S272 has been located on the physical map between D16S288 and D16S299. Restriction mapping has demonstrated the location of possible CpG islands. One gene, STP, has been localised on the YAC contig proximal to D16S298 and is therefore a candidate for CLN3. Other genes, including IL4R, SGLT2, and UQCRC2, have been excluded from this region. © 1995 Wiley-Liss, Inc. 相似文献