7,052 research outputs found
Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.
No full textThe MLL gene located at 11q23 has been described as a 'promiscuous' gene due its involvement with a large number of genetic partners. The EU Concerted Action Workshop on 11q23 provided 550 cases for study of which 82 showed abnormalities which did not involve the established translocations or deletion of 11q23. In these 'other' cases, which included inversions and duplications, 11q23 was found to be involved with 25 chromosome partners of which 10 had not been previously reported. These were 1q31, 4p11, 6q13, 8q21, 10q22, 10q25, 11q11, 11q21, 13q34 and 18q23. This study demonstrated the value of the Workshop, in confirming the diversity of chromosomal partner sites involved with 11q23 and in the identification of new partners
Acquired abnormalities of chromosome 21 in acute lymphoblastic leukaemia
No full textThe intrachromosomal amplification of chromosome 21 (iAMP21) was identifiedas a novel and prognositically important acquired chromosomal abnormality inchildhood acute lymphoblastic leukaemia (ALL). It is defined by multiple copiesof the RUNX1 gene, as seen by fluorescence in situ hybridisation (FISH), localisedto a single abnormal duplicated chromosome 21 [dup(21)]. The morphologicalform of this chromosome is highly variable between patients and currently theonly reliable method of detection is FISH with probes to RUNX1. Studies of 48iAMP21 patients using detailed FISH techniques and array-based comparativegenomic hybridisation highlighted an extensive region of chromosome 21involvement. A minimum common region of amplification, between 33.19 and39.80Mb, including RUNX1 was identified, together with a minimum commonregion of deletion, between 46.54 and 46.92Mb, in 100% and 77% of patients,respectively. This study established that there were unique patterns of imbalance,with evidence of deletions, inversions and amplification, displayed on thedup(21), between individual patients. This provided evidence of an abnormalitythat may have arisen from a breakage-fusion-bridge mechanism, possibly initiatedby loss of a telomere. Results indicated that iAMP21 represents a distinct geneticsubgroup of childhood ALL and is not secondary to a cryptic abnormality ofchromosome 21. Two possible variant cases were identified both involvingchromosome 15. The abnormality can be distinguished from other numericalabnormalities of chromosome 21 by exploiting the unique pattern of gain,amplification and deletion seen in these patients. This allowed for thedevelopment of diagnostic tests based on copy number using either FISH ormultiplex ligation dependent probe amplification (MLPA), both of whichsuccessfully identified iAMP21 patients
Competing conventions: The Big Branders’ struggle to incorporate new quality conceptions in the Norwegian food market
Get PDFThe paper addresses recent changes in the Norwegian agrifood industry from the analytical perspective of quality conventions. Storper and Salais’ “worlds of production” plus Boltanski and Thévenots’ “orders of worth” are used as a basis for the empirical study. First, the paper discusses how the largest Norwegian branders try to strategically adapt to “novel” quality attributes like health-enhancing food, origin/terroir, environmental sustainability and ethics. Second, the paper investigates the companies’ quality signalling strategy: How are these “novel” qualities communicated to consumers? Multiple options are available: Do they attempt to systematically incorporate “novel qualities” into their private brand equity (“conventionalizing qualities”)? Do they prefer a co-labelling scheme with a third party control, or do they use any other measures for quality signalling? The paper thereby discusses how the largest Norwegian branders in the food sector cope with conflicting and competing quality conventions.Food quality, economics of convention., Food Consumption/Nutrition/Food Safety,
The sophisticated architecture of the rat atrioventricular node
Get PDFIn the mammalian heart, the action potential spontaneously generated in the sinoatrial (SA) node propagates through the atria to reach the atrioventricular (AV) node. As the only conduction pathway between the atria and ventricles, the AV node functions to delay and regulate action potential conduction between the atria and ventricles. Since Tawara described the anatomical and morphological characteristics of the AV node in 1906, it has been difficult to correlate electrophysiological recordings with distinct cell types and the three dimensional
structure of the AV node due to the exceptional functional and architectural complexity of this region. The cardiac voltage-gated Na+ channel isoform (Na1.5) is known to play a major role in the generation and conduction of the action potential in the heart. Recently, various mutations of
Na, 1.5 responsible for AV conduction block and Na,, 1.5+/- mice with impaired AV conduction have been reported. Various neuronal Na' channel isoforms have also been shown to be expressed in the heart (mouse ventricular myocytes and rat and mouse SA node) and to be functionally important. The distribution of neuronal Na channel isoforms in the AV node is unknown. The aim of this study was to investigate the distribution of cardiac and neuronal Na'channel isoforms in and around the AV node.
The nodal cell region was identified by Masson's trichrome staining and confocal microscopy with immunohistochemical markers, such as connexin43 (Cx43), desmoplakin(DP), atrial natriuretic peptide (ANP) and the type 4 hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel. The unique pattern of expression in the nodal cell region (DP-positive/Cx43-negative/ANP-negative/HCN4-positive) allowed it to be distinguished from the surrounding working myocardium (DP-positive/Cx43-positive/HCN4-negative).
I have investigated the expression of Na,1.5 and other Na+ channel isoforms in rat AV node. Na1.1 was distributed in a similar manner to Na1.5, Na1.2 was not detected. Na1.3
labelling was restricted to nerve fibres and nerve cell bodies and was not detected in myocytes.Na1.3 labelling was abundant in the enclosed node and the common bundle, but much less abundant in other regions. Na1.4, the skeletal isoform, was not studied. Na1.5 labelling was present in atrial and ventricular myocardium and the left bundle branch (right not studied). However, Na1.5 labelling was absent in the open node, the enclosed node and the common
bundle, but present at a reduced level in the posterior nodal extension, transitional cells and AV ring bundle. Na 1.6 was not detected.
The study has revealed a complex organisation of three different myocyte types at the AV junction (including the tricuspid annulus). Impaired AV conduction as a result of mutations in or loss of Na1.5 must be the result of impaired conduction in the AV node inputs (posterior
nodal extension and transitional cells) or output (bundle branch) rather than the AV node itself (open and enclosed nodes)
Does TP53 guard ALL genomes?
No full textIn this issue of Blood, Stengel et al advance our knowledge of the genomic landscape of acute lymphoblastic leukemia (ALL) by demonstrating a high frequency of TP53 mutations in specific genetic subtypes
One man\u27s dose, another man\u27s poison
No full textIn this issue of Blood, Dulucq and colleagues report that genetic polymorphisms in the promoter of dihydrofolate reductase (DHFR) are linked to expression and outcome in childhood acute lymphoblastic leukemia (ALL)
New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia
No full textA cute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyperdiploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are highrisk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL
The clinical relevance of chromosomal and genomic abnormalities in B-cell precursor acute lymphoblastic leukaemia
No full textAcute lymphoblastic leukaemia (ALL) occurs at all ages but is the most common cancer of childhood. The current treatment of paediatric ALL is highly successful with up to 90% children being cured. In contrast, survival rates for adult ALL are significantly lower at around 40%. The discovery and characterisation of genetic abnormalities have increased our understanding of the biology of the disease and provided important prognostic and predictive markers which have improved patient outcome. Not only is the spectrum of these aberrations vast but, due to advances in technology, continually expanding. A wide range of chromosomal and genomic abnormalities have been reported as being associated with patient outcome but only a subset are currently used to risk stratify patients. This review highlights the main genetic abnormalities which are used to manage patients with B-cell precursor ALL and discusses the evidence which has been accumulated on several newly described genomic abnormalities. (C) 2012 Elsevier Ltd. All rights reserved
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