18 research outputs found

    Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

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    Outcomes of long left coronary endarterectomy in patients with diffuse coronary artery disease

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    Aim: Historically the outcome of left coronary artery endarterectomy (LCAE) has been associated with increased morbidity and mortality when surgeons performed it with coronary artery bypass grafting (CABG). We aim to review outcomes after open LCAE-CABG in patients managed with aggressive dual antiplatelet therapy.Methods: From 1999 to 2007 open LCAE with CABG was performed in 87 patients. We compared the short and long-terms outcomes of 75 propensity-matched conventional CABG patients. Both groups were operated on by a single surgeon.Results: Sixty-six percent (66%; n = 58/87) of LCAE group had diffuse atheroma in Left anterior descending artery (LAD); 31% (n = 27/87) involved both LAD and branches of the circumflex artery (Cx); 3%; (n = 3/87) involved the Cx in isolation. Cross clamp time (43.29 vs. 59.04, P = 0.019) and bypass time (57.29 vs. 74.04, P = 0.007) were significantly higher in the LCAE group. There was no significant difference in early (1% vs. 1.3%) and late mortality (4% vs. 4.5% at 10 years). The hospital length of stay (5.58 vs. 6.67, P = 0.03), was higher in the LACE group when compared with the CABG group. The freedom from angina and long-term survival were not significantly different between the two groups.Conclusion: Patients undergoing CABG with Left-sided coronary endarterectomy had increased cross-clamp and bypass times with prolonged stay in hospital and increased blood transfusion rates. The mortality, morbidity, long-term survival and freedom from angina are not different when compared to CABG alone. The use of retrograde blood cardioplegia and aggressive antiplatelets may have contributed to the excellent outcome

    NAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairment

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    We report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family’s disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA. In vitro assays for the p.Tyr43Ser mutant enzyme showed a significant decrease in catalytic activity and reduced stability compared to wild-type Naa10 protein. NAA10 has previously been associated with Ogden syndrome, Lenz microphthalmia syndrome and non-syndromic developmental delay. Our findings expand the clinical spectrum of NAA10 and suggest that the proposed correlation between mutant Naa10 enzyme activity and phenotype severity is more complex than anticipated; the p.Tyr43Ser mutant enzyme has less catalytic activity than the p.Ser37Pro mutant associated with lethal Ogden syndrome but results in a milder phenotype. Importantly, we highlight the need for cardiac assessment in males and females with NAA10 variants as both patients and carriers can have long QT

    Cell Populations Expressing Stemness-Associated Markers in Lung Adenocarcinoma

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    The stemness-associated markers OCT4, NANOG, SOX2, KLF4 and c-MYC are expressed in numerous cancer types suggesting the presence of cancer stem cells (CSCs). Immunohistochemical (IHC) staining performed on 12 lung adenocarcinoma (LA) tissue samples showed protein expression of OCT4, NANOG, SOX2, KLF4 and c-MYC, and the CSC marker CD44. In situ hybridization (ISH) performed on six of the LA tissue samples showed mRNA expression of OCT4, NANOG, SOX2, KLF4 and c-MYC. Immunofluorescence staining performed on three of the tissue samples showed co-expression of OCT4 and c-MYC with NANOG, SOX2 and KLF4 by tumor gland cells, and expression of OCT4 and c-MYC exclusively by cells within the stroma. RT-qPCR performed on five LA-derived primary cell lines showed mRNA expression of all the markers except SOX2. Western blotting performed on four LA-derived primary cell lines demonstrated protein expression of all the markers except SOX2 and NANOG. Initial tumorsphere assays performed on four LA-derived primary cell lines demonstrated 0–80% of tumorspheres surpassing the 50 µm threshold. The expression of the stemness-associated markers OCT4, SOX2, NANOG, KFL4 and c-MYC by LA at the mRNA and protein level, and the unique expression patterns suggest a putative presence of CSC subpopulations within LA, which may be a novel therapeutic target for this cancer. Further functional studies are required to investigate the possession of stemness traits

    Influence of baroreflex-mediated tachycardia on the regulation of dynamic cerebral perfusion during acute hypotension in humans

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    The effect of acute arterial baroreflex dysfunction on cerebral autoregulation (CA) in otherwise healthy humans is unknown. We identified dynamic CA with and without arterial baroreflex-mediated tachycardia and consequent changes in cardiac output during acute hypotension whilst continuously monitoring changes in middle cerebral artery mean blood velocity (MCA Vmean). Acute hypotension was induced in nine healthy subjects (mean ±s.d.; 26 ± 3 years) by releasing bilateral thigh cuffs after 6 min of supra-systolic resting ischaemia. Hypotension was induced before and after sympathetic blockade (β-1 receptors), and combined sympathetic–cholinergic blockade. That sequential bolus injections of sodium nitroprusside (50 μg), followed 60 s later by phenylephrine hydrochloride (50 μg), elicited < 5 beats min−1 change in heart rate was verified to confirm that full cardiac autonomic blockade was achieved. Thigh cuff release elicited a transient drop in mean arterial pressure and resultant tachycardia. This tachycardic response was diminished in full cardiac blockade (vs. control, P= 0.029; vs.β-1 adrenergic blockade, P= 0.031). Dynamic CA was also attenuated in the full blockade condition compared to both control (P= 0.028) and β-1 adrenergic blockade conditions (P= 0.015), and was related with the attenuated tachycardia response (P= 0.015). These data indicate an important role of the cardiac baroreflex in dynamic CA

    Complete Genome Sequence of the Oral Pathogenic Bacterium Porphyromonas gingivalis Strain W83

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    The complete 2,343,479-bp genome sequence of the gram-negative, pathogenic oral bacterium Porphyromonas gingivalis strain W83, a major contributor to periodontal disease, was determined. Whole-genome comparative analysis with other available complete genome sequences confirms the close relationship between the Cytophaga-Flavobacteria-Bacteroides (CFB) phylum and the green-sulfur bacteria. Within the CFB phyla, the genomes most similar to that of P. gingivalis are those of Bacteroides thetaiotaomicron and B. fragilis. Outside of the CFB phyla the most similar genome to P. gingivalis is that of Chlorobium tepidum, supporting the previous phylogenetic studies that indicated that the Chlorobia and CFB phyla are related, albeit distantly. Genome analysis of strain W83 reveals a range of pathways and virulence determinants that relate to the novel biology of this oral pathogen. Among these determinants are at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases. Genome analysis also reveals that P. gingivalis can metabolize a range of amino acids and generate a number of metabolic end products that are toxic to the human host or human gingival tissue and contribute to the development of periodontal disease
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