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Biomedical subjects

Elizabeth Cooper

Publications and source records attributed to Elizabeth Cooper.

9 recordsLinked to original sources
PubMed2005

Subtype-specific regulation of equilibrative nucleoside transporters by protein kinase CK2.

Two subtypes of equilibrative transporters, es (equilibrative inhibitor-sensitive) and ei (equilibrative inhibitor-insensitive), are responsible for the majority of nucleoside flux across mammalian cell membranes. Sequence analyses of the representative genes, ENT1 {equilibrative nucleoside transporter 1; also known as SLC29A1 [solute carrier family 29 (nucleoside transporters), member 1]} and ENT2 (SLC29A2), suggest that protein kinase CK2-mediated phosphorylation may be involved in the regulation of es- and ei-mediated nucleoside transport. We used human osteosarcoma cells transfected with catalytically active or inactive alpha' and alpha subunits of CK2 to assess the effects of CK2 manipulation on nucleoside transport activity. Expression of inactive CK2alpha' (decreased CK2alpha' activity) increased the number of binding sites (approximately 1.5-fold) for the es-specific probe [3H]NBMPR ([3H]nitrobenzylthioinosine), and increased (approximately 1.8-fold) the V(max) for 2-chloro[3H]adenosine of the NBMPR-sensitive (es) nucleoside transporter. There was a concomitant decrease in the V(max) of the NBMPR-resistant (ei-mediated) uptake of 2-chloro[3H]adenosine. This inhibition of CK2alpha' activity had no effect, however, on either the K(D) of [3H]NBMPR binding or the K(m) of 2-chloro[3H]adenosine uptake. Quantitative PCR showed a transient decrease in the expression of both hENT1 (human ENT1) and hENT2 mRNAs within 4-12 h of induction of the inactive CK2alpha' subunit, but both transcripts had returned to control levels by 24 h. These data suggest that inhibition of CK2alpha' reduced ei activity by attenuation of hENT2 transcription, while the increase in es/hENT1 activity was mediated by post-translational action of CK2. The observed modification in es activity was probably due to a CK2alpha'-mediated change in the phosphorylation state of the ENT1 protein, or an interacting protein, effecting an increase in the plasma membrane lifetime of the transport proteins.

2-Chloroadenosine↗
PubMed2005

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome.

Previous work by others have suggested the occurrence of one or more chemical or metabolic 'markers' for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups. Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed. Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.

Acids↗
PubMed2005

Onychomycosis: a critical study of techniques and criteria for confirming the etiologic significance of nondermatophytes.

Nondermatophytic filamentous fungi (NDF) other than Scytalidium species are variously said to cause between 0 and 50% of all toenail onychomycoses, though most estimates are in the 2-5% range. Due to the difficulty of obtaining 'gold standard' control data for comparison, the accuracy of many laboratory evaluation processes used to deal with potential NDF onychomycoses has never been rigorously measured, thus allowing use of differing interpretations of the significance of cultures. To allow valid comparison of these procedures and interpretations, a large series of patients who declined treatment were sampled on multiple occasions from all apparently onychomycotic toenails until adequate certainty had been attained that all etiologic agents had been isolated and, where necessary, confirmed as etiologic via consistent repeated isolation. This information was used to evaluate results that had been obtained in the initial direct microscopy and culture studies for the same patient population, as such results are strongly relied on in routine diagnosis. Direct microscopy (KOH) was found to be 73.8% sensitive for dermatophytes and 67.2% sensitive for proven etiologic NDF (difference not significant). Culture of the initial specimen coincidentally had a sensitivity of 74.6% for both fungal groups. KOH and culture in tandem were 83.9% sensitive for indicating fungal etiology based on the first specimen. Different evaluative frameworks currently used to interpret NDF isolations were contrasted. The 'classic' evaluation procedure, in which all NDF considered etiologic must be isolated from at least two successive nail specimens, at least one of which must be microscopic positive for compatible fungal filaments, had a sensitivity of 59.5% but a specificity of 100% for true NDF infections and mixed NDF/dermatophyte infections. The most widely used 'simple association' evaluation criterion, in which NDF outgrowth is considered etiologic whenever direct microscopy is positive for fungal elements and no dermatophyte grows out from the initial specimen, had a sensitivity of 53.6% and a specificity of 70.3% for NDF infections. A frequently criticized, but in some quarters still advocated, variant of the simple association criterion considers NDF outgrowth to be significant whenever the corresponding specimen is positive for fungal filaments in direct microscopy; application of this criterion yielded a sensitivity of 60.7% for true infections but a specificity of only 42%. With the aid of two standard notes soliciting repeat specimens, the classic criterion was able to attain 92.7% accuracy in recognizing all NDF etiologic agents and 100% accuracy in disregarding all contaminants from initial specimens that were positive in direct microscopy and yielded a filamentous fungus in initial culture. Even in exhaustive longitudinal study, only 20.2% of NDF infections were found to be associated with a concurrent dermatophytosis. In auxiliary studies, some nails remained NDF-infected after dermatophytes had been successfully eliminated by therapy.

Arthrodermataceae↗
PubMed2005

A norovirus gastroenteritis epidemic in a long-term-care facility.

BACKGROUND: In Victoria, Australia, from July to December 2002, 126 outbreaks of viral and suspected viral gastroenteritis were reported in healthcare institutions. Norovirus was found to account for at least 77 of the 126 outbreaks. METHODS: In October 2002, the infection control unit investigated an outbreak of acute gastroenteritis on three wards in a 500-bed, long-term-care facility in Melbourne, Victoria, Australia. Cohorting and other infection control measures were initiated. RESULTS: The outbreak was controlled 32 days after the first symptoms of acute gastroenteritis were identified. Fifty-two patients and 11 staff members were affected. Norovirus genotype 2 was detected on two of the three wards. Norovirus was not isolated in the third ward but was suspected to be the causative organism. CONCLUSIONS: Outbreaks of viral gastroenteritis can cause significant morbidity in a long-term-care facility, affecting both patients and staff. In addition, the transmission of viral pathogens can be well established before there is recognition of an outbreak.

Australia↗
PubMed2002

Characteristics of a large cluster of vancomycin-resistant enterococci in an Australian hospital.

Investigation of a cluster of hospital inpatients colonized with vancomycin-resistant enterococci (VRE) revealed a point-prevalence of 19.1%. The outbreak was controlled using established guidelines and additional strategies, including minimizing patient transfers and enforcing appropriate antibiotic prescribing. The incidence of VRE has remained low during the ensuing 30 months.

Anti-Bacterial Agents↗