Differential metabolism of deoxyribonucleosides by leukaemic T cells of immature and mature phenotype

Experimental evidence has indicated that T lymphoblasts are more sensitive to deoxynucleoside toxicity than are B lymphoblasts. These data have led to the use of purine enzyme inhibitors as selective chemotherapeutic drugs in the treatment of T cell malignancies ranging from T cell acute lymphoblastic leukaemia to cutaneous T cell lymphomas. We have compared the toxicities of 2′-deoxyadenosine, 2′-deoxyguanosine, and thymidine for T cell lines derived from patients with T cell acute lymphoblastic leukaemia with those for mature T cell lines derived from patients with cutaneous T cell leukaemia/lymphoma. We have found that both deoxynucleosides are far less toxic to the mature T cell lies than to T lymphoblasts and that the mature cells accumulate much lower amounts of dATP and dGTP when exposed to deoxyadenosine and deoxyguanosine, respectively. Similar studies performed on peripheral blood cells from patients with T cell leukaemias of mature phenotype and on peripheral blood T cells demonstrate similar low amounts of deoxynucleotide accumulation. Measurements of the activities of several purine metabolizing enzymes that participate in deoxynucleoside phosphorylation or degradation do not reveal differences which would explain the toxicity of deoxynucleosides for immature, as compared to mature, T cells. We conclude that deoxynucleoside metabolism in leukaemic T cells varies with their degree of differentiation. These observations may be relevant to the design of chemotherapeutic regimes for T cell malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72479/1/j.1365-2141.1985.tb04067.x.pd

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: a longitudinal study

Background Pulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are detectable in the sputum, plasma and urine of adults with CF, suggesting that they have potential as biomarkers for P. aeruginosa infection. Aim To investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P. aeruginosa infection. Methods A multicentre observational study of 176 adults and 68 children with CF. Cross-sectionally, comparisons were made between current P. aeruginosa infection using six 2-alkyl-4-quinolones detected in sputum, plasma and urine against hospital microbiological culture results. All participants without P. aeruginosa infection at baseline were followed up for one year to determine if 2-alkyl-4-quinolones were early biomarkers of pulmonary P. aeruginosa infection. Results Cross-sectional analysis: the most promising biomarker with the greatest diagnostic accuracy was 2-heptyl-4-hydroxyquinoline (HHQ). In adults, areas under the ROC curves (95% confidence intervals) for HHQ analyses were 0.82 (0.75–0.89) in sputum, 0.76 (0.69–0.82) in plasma and 0.82 (0.77–0.88) in urine. In children, the corresponding values for HHQ analyses were 0.88 (0.77–0.99) in plasma and 0.83 (0.68–0.97) in urine. Longitudinal analysis: Ten adults and six children had a new positive respiratory culture for P. aeruginosa in follow-up. A positive plasma HHQ test at baseline was significantly associated with a new positive culture for P. aeruginosa in both adults and children in follow-up (odds ratio (OR) = 6.67;-95% CI:-1.48–30.1;-p = 0.01 and OR = 70; 95% CI: 5–956;-p < 0.001 respectively). Conclusions AQs measured in sputum, plasma and urine may be used to diagnose current infection with P. aeruginosa in adults and children with CF. These preliminary data show that plasma HHQ may have potential as an early biomarker of pulmonary P. aeruginosa. Further studies are necessary to evaluate if HHQ could be used in clinical practice to aid early diagnosis of P. aeruginosa infection in the future

Inhomogeneous States in a Small Magnetic Disk with Single-Ion Surface Anisotropy

We investigate analytically and numerically the ground and metastable states for easy-plane Heisenberg magnets with single-ion surface anisotropy and disk geometry. The configurations with two half-vortices at the opposite points of the border are shown to be preferable for strong anisotropy. We propose a simple analytical description of the spin configurations for all values of a surface anisotropy. The effects of lattice pinning leads to appearance of a set of metastable configurations.Comment: 10 pages, 7 figures; submitted to Phys. Rev.

Small animal disease surveillance:Pruritus and Pseudomonas skin infections

Report Summary: • Presentation for investigation and/or treatment of gastrointestinal (GI) disease comprised 3.0 per cent, 2.0 per cent and 1.9 per cent of total dog, cat and rabbit consultations respectively between 1 April 2017 and 31 October 2018 • Diarrhoea and vomiting without blood were the most frequently reported GI disease clinical signs (43.0 and 36.6 per cent in dogs, and 35.9 and 37.7 per cent in cats respectively) • The proportion of GI disease consultations which prescribed antibiotics authorised for systemic administration (including oral and injectable formulations) decreased between April 2014 and October 2018 • The proportion of GI disease consultations which dispensed nutraceutical products advertised as being effective at managing primary GI disease (including prebiotics, probiotics etc.) increased between April 2014 and October 2018 • Between January 2011 and August 2018, 13.5 per cent of 20,194 feline faecal samples submitted to UK-based diagnostic laboratories tested positive for presence of Tritrichomonas foetus • The proportion of feline sample submissions testing positive for T.foetus decreased between 2011 and 201

Cross-domain interference costs during concurrent verbal and spatial serial memory tasks are asymmetric

Some evidence suggests that memory for serial order is domain-general. Evidence also points to asymmetries in interference between verbal and visual-spatial tasks. We confirm that concurrently remembering verbal and spatial serial lists provokes substantial interference compared with remembering a single list, but we further investigate the impact of this interference throughout the serial position curve, where asymmetries are indeed apparent. A concurrent verbal order memory task affects spatial memory performance throughout the serial positions of the list, but performing a spatial order task affects memory for the verbal serial list only for early list items; in the verbal task only, the final items are unaffected by a concurrent task. Adding suffixes eliminates this asymmetry, resulting in impairment throughout the list for both tasks. These results suggest that domain-general working memory resources may be supplemented with resources specific to the verbal domain, but perhaps not with equivalent spatial resources

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd