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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Platelet beta-secretase activity is increased in Alzheimer's disease.

beta-Secretase activity is the rate-limiting step in Abeta peptide production from amyloid precursor protein. Abeta is a major component of Alzheimer's disease (AD) cortical amyloid plaques. beta-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether beta-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric beta-secretase activity assay to investigate platelets isolated from individuals with AD (n=86), and age-matched controls (n=115). Platelet membrane beta-secretase activity (expressed as initial rate) varied over fourfold between individuals, raising important questions about in vivo regulation of this proteolytic activity. Nonetheless, we identified a significant 17% increase in platelet membrane beta-secretase activity in individuals with AD compared to controls (p=0.0003, unpaired t-test). Platelet membrane beta-secretase activity did not correlate with mini-mental state examination (MMSE) score in the AD group (mean MMSE=17.7, range 1-23), indicating that the increase did not occur as a secondary result of the disease process, and may even have preceded symptom onset.

Aged↗
PubMed2006

Validation of a self-completion measure of breakfast foods, snacks and fruits and vegetables consumed by 9- to 11-year-old schoolchildren.

OBJECTIVE: To evaluate the validity and reliability of a dietary recall questionnaire, designed for group-level comparisons of foods eaten at breakfast and intake of fruits, vegetables, sweet items and crisps. DESIGN: Validity was assessed relative to 24-h dietary recall interviews, and reliability by comparing the baseline data with 4-month follow-up data. SUBJECTS AND SETTING: Fifty-eight schools took part in the validity assessments, with 374 children completing both measures. Reliability was assessed using 29 schools, with 1233 children at baseline and 1033 at follow-up. Children were aged 9-11 years and schools were located in socio-economically deprived areas of Wales. RESULTS: Results indicated moderate to substantial agreements for most foods eaten at breakfast on the day of reporting and fair to moderate agreements for breakfast foods the previous day. For items throughout the rest of the previous day, agreement was fair to substantial during school hours, but slight after school. Correlations were moderate in terms of 'healthy' items and 'unhealthy' items consumed at breakfast on the day of reporting, but weaker for the previous breakfast. Correlations between measures in terms of fruits, vegetables, sweet items and crisps throughout the rest of the previous day were fair to moderate. The measure demonstrated fair to substantial group-level reliability. CONCLUSIONS: The questionnaire, while subject to a number of limitations, gives an adequately valid and reliable overview of selected aspects of children's diet. It is likely to be of value at group-level in randomized controlled trials of school-based interventions.

Child↗
PubMed2006

COX-1 and COX-2 expression in feline oral squamous cell carcinoma.

This study demonstrated immunohistochemically the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in feline oral squamous cell carcinoma (FOSCC), with primary polyclonal antibodies raised against human epitopes. COX-2 immunolabelling was intracytoplasmic and, in some neoplastic cells, perinuclear; it was demonstrated in a small proportion (< or = 1%) of neoplastic cells and its intensity was usually mild to moderate. In contrast, all neoplastic tissues showed extensive nuclear and cytoplasmic COX-1 immunolabelling. Cytoplasmic COX-1 immunolabelling was less intense than nuclear labelling in neoplastic tissue. In the adjacent histologically normal oral mucosa, COX-2 immunolabelling was absent. The cytoplasmic and nuclear intensity and distribution of COX-1 immunolabelling was significantly higher in neoplastic tissue than in adjacent normal oral mucosa. The results indicate that COX-1 and COX-2 are overexpressed in FOSCC, but the clinical and pathophysiological significance of this finding remains to be determined.

Animals↗
PubMed2006

Experimental infection of big brown bats (Eptesicus fuscus) with Eurasian bat lyssaviruses Aravan, Khujand, and Irkut virus.

Here we describe the results of experimental infections of captive big brown bats (Eptesicus fuscus) with three newly isolated bat lyssaviruses from Eurasia (Aravan, Khujand, and Irkut viruses). Infection of E. fuscus was moderate (total, 55-75%). There was no evidence of transmission to in-contact cage mates. Incubation periods for Irkut virus infection were significantly shorter (p < 0.05) than for either Aravan or Khujand virus infections. In turn, quantification of viral RNA by TaqMan PCR suggests that the dynamics of Irkut virus infection may differ from those of Aravan/Khujand virus infection. Although infectious virus and viral RNA were detected in the brain of every rabid animal, dissemination to non-neuronal tissues was limited. Levels of viral RNA in brain of Aravan/Khujand virus-infected bats was significantly correlated with the number of other tissues positive by TaqMan PCR (p < 0.05), whereas no such relationship was observed for Irkut virus infection (where viral RNA was consistently detected in all tissues other than kidney). Infectious virus was isolated sporadically from salivary glands, and both infectious virus and viral RNA were obtained from oral swabs. The detection of viral RNA in oral swabs suggests that viral shedding in saliva occurred <5 days before the onset of clinical disease.

Animals↗
PubMed2006

Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours.

Between 1997 and 1999, 280 dogs with mast cell tumours were identified, of which 59 (21 per cent) had multiple tumours. Follow-up data for survival analysis were available for 145 dogs with single tumours and 50 dogs with multiple tumours. There was no significant difference between the survival times of the two groups; the survival rates after 12 and 24 months were 88 per cent and 83 per cent, respectively, for the dogs with single tumours, and 86 per cent at both intervals for the dogs with multiple tumours. Eight of the dogs with single tumours had lymph node metastases (stage II disease) and these dogs had a median survival time of 431 days, whereas the 50 dogs with multiple tumours (classified as stage III disease) and the dogs with single tumours (classified as stage I disease) had not reached their median survival times. Golden retrievers appeared to be predisposed to developing multiple tumours in the population studied, with an odds ratio of 3.8. This study found no evidence that dogs with multiple tumours had different survival times than those with single tumours, although there was evidence that the presence of lymph node metastasis generally carried a poorer prognosis.

Animals↗
PubMed2006

Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

Animals↗
PubMed2006

Multiple limbal haemangiosarcomas in a border collie dog: management by lamellar keratectomy/sclerectomy and strontium-90 beta plesiotherapy.

An eight-year-old, neutered, male border collie dog was presented with a six-week history of left ocular discomfort and a raised, red mass at the lateral limbus. The right eye had been enucleated approximately 12 months previously following suspected trauma when the eye had become red and painful. The mass was excised using superficial keratectomy/sclerectomy and the surgery site was treated with strontium-90 beta radiation. Histopathological findings were consistent with a diagnosis of haemangiosarcoma. Immunohistochemical staining showed uniform expression of CD31 in neoplastic cells, confirming their endothelial origin. Two further treatments with strontium-90 beta radiation were applied to the surgical site at weekly intervals. Twenty-six weeks after surgery, a second, raised, red limbal mass became apparent at the medial limbus of the left eye. Surgical excision and adjuvant strontium-90 beta plesiotherapy were performed as described for the initial tumour. Routine histopathological analysis confirmed haemangiosarcoma at this site. Eighty-six weeks following the initial presentation, no recurrence of ocular haemangiosarcoma was evident.

Animals↗
PubMed2006

Intermandibular malignant mesenchymoma in a crossbreed dog.

A 12-year-old German shepherd crossbreed dog was presented with a submandibular mass that was initially diagnosed as myxosarcoma on incisional biopsy. Chest radiographs were taken for staging, and magnetic resonance imaging was performed to assess the feasibility of cytoreductive surgery before adjuvant radiotherapy. The dog underwent debulking surgery, and histology permitted reclassification of the tumour as a malignant mesenchymoma (with myxosarcomatous and osteosarcomatous differentiation). The dog was subsequently treated with four fractions of radiotherapy given at seven-day intervals and three doses of carboplatin. The dog remained stable following therapy until its condition acutely deteriorated, and it was euthanased 153 days after surgery. On postmortem examination, there were no signs of local tumour recurrence, but metastases were observed both in the thorax and in the abdomen.

Animals↗
PubMed2005

Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway.

We investigated the ability of a selection of human influenza A viruses, including recent clinical isolates, to induce IFN-beta production in cultured cell lines. In contrast to the well-characterized laboratory strain A/PR/8/34, several, but not all, recent isolates of H3N2 viruses resulted in moderate IFN-beta stimulation. Through the generation of recombinant viruses, we were able to show that this is not due to a loss of the ability of the NS1 genes to suppress IFN-beta induction; indeed, the NS1 genes behaved similarly with respect to their abilities to block dsRNA signaling. Interestingly, replication of A/Sydney/5/97 virus was less susceptible to pre-treatment with IFN-alpha than the other viruses. In contrast to the universal effect on dsRNA signaling, we noted differences in the effect of NS1 proteins on expression of interferon stimulated genes and also genes induced by a distinct pathway. The majority of NS1 proteins blocked expression from both IFN-dependent and TNF-dependent promoters by an apparent post-transcriptional mechanism. The NS1 gene of A/PR/8/34 NS1 did not confer these blocks. We noted striking differences in the cellular localization of different influenza A virus NS1 proteins during infection, which might explain differences in biological activity.

Animals↗
PubMed2005

Public health monitoring tools for multiple data streams.

INTRODUCTION: In concert with increased concerns regarding both biologic terrorism and new natural infectious disease threats (e.g., severe acute respiratory syndrome [SARS] and West Nile virus), as a result of advances in medical informatics, various data sources are available to epidemiologists for routine, prospective monitoring of public health. The synthesis of this evidence requires tools to find anomalies within various data stream combinations while maintaining manageable false alarm rates. OBJECTIVES: The objectives of this report are to establish statistical hypotheses to define the compound multivariate problem of surveillance systems, present statistical methods for testing these hypotheses, and examine results of applying these methods to simulated and actual data. METHODS: Canonical problems of parallel monitoring and consensus monitoring are considered in this report. Modified Bonferroni methods are examined for parallel monitoring. Both multiple univariate and multivariate methods are applied for consensus monitoring. A multivariate adaptation of Monte Carlo trials, using the injection of epidemic-curve-like signals in the multiple data streams of interest, is presented for evaluation of the various tests. RESULTS: The Monte Carlo test results demonstrate that the multiple univariate combination methods of Fisher and Edgington provide the most robust detection performance across the scenarios tested. As the number of data streams increases, methods based on Hotelling's T2 offer added sensitivity for certain signal scenarios. This potential advantage is clearer when strong correlation exists among the data streams. CONCLUSION: Parallel and consensus monitoring tools must be blended to enable a surveillance system with distributed sensitivity and controlled alert rates. Whether a multiple univariate or multivariate approach should be used for consensus monitoring depends on the number and distribution of useful data sources and also on their covariance structure and stationarity. Strong, consistent correlation among numerous sources warrants the examination of multivariate control charts.

Algorithms↗
PubMed2005

Atomic scale spin-dependent STM on magnetite using antiferromagnetic STM tips.

STM tips made from antiferromagnetic MnNi have been used to investigate the atomic structure of the (001) and (111) surfaces of Fe3O4. The clean (001) surface displays a ( radical2 x radical2)R45 degrees superlattice, which is attributed to charge-ordering on the surface, where Fe(2+)-Fe2+ and Fe(3+)-Fe3+ dimers can be discriminated. The oxygen-terminated (111) surface is characterized by a hexagonal superlattice with a periodicity of 42 A. Oxygen vacancies are observed in atomically resolved images of this superlattice. In the presence of an external magnetic field of 60 mT, a significant change in the atomic corrugation in the topmost oxygen layer around each of these defects is observed. The results on both (001) and (111) surfaces are discussed in terms of possible spin-polarized effects.

Crystallography↗
PubMed2005

Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease.

Several lines of evidence indicate that the Abeta peptide is involved at some level in the pathological process that results in the clinical symptoms of AD (Alzheimer's disease). The N-terminus of Abeta is generated by cleavage of the Met-Asp bond at position 671-672 of APP (amyloid precursor protein), catalysed by a proteolytic activity called beta-secretase. Two 'beta-secretase' proteases have been identified: BACE (beta-site APP-cleaving enzyme) and BACE2. The cause of sporadic AD is currently unknown, but some studies have reported elevated BACE/beta-secretase activity in brain regions affected by the disease. We have demonstrated that robust beta-secretase activity is also detectable in platelets that contain APP and release Abeta. This review considers the current evidence for alterations in beta-secretase activity, and/or alterations in BACE expression, in post-mortem brain tissue and platelets from individuals with AD.

Alzheimer Disease↗
PubMed2005

Caregiver burden, time spent caring and health status in the first 12 months following stroke.

OBJECTIVE: To quantify time caring, burden and health status in carers of stroke patients after discharge from rehabilitation; to identify the potentially modifiable sociodemographic and clinical characteristics associated with these outcomes. METHODS: Patients and carers prospectively interviewed 6 (n=71) and 12 (n=57) months after discharge. Relationships of carer and patient variables with burden, health status and time analysed by Gaussian and Poisson regression. RESULTS: Carers showed considerable burden at 6 and 12 months. Carers spent 4.6 and 3.6 hours per day assisting patients with daily activities at 6 and 12 months, respectively. Improved patient motor and cognitive function were associated with reductions of up to 20 minutes per day in time spent in daily activities. Better patient mental health and cognitive function were associated with better carer mental health. CONCLUSIONS: Potentially modifiable factors such as these may be able to be targeted by caregiver training, support and education programmes and outpatient therapy for patients.

Activities of Daily Living↗
PubMed2005

Implications of increased haemoglobin A2 values in HIV positive women in the antenatal clinic.

Universal antenatal haemoglobinopathy screening in this hospital has identified several women with increased haemoglobin A(2) values, but without hypochromic microcytic red cell indices. This report describes two cases where there is evidence that the raised haemoglobin A(2) value is not caused by heterozygous beta thalassaemia, but rather results from these patients being human immunodeficiency virus (HIV) positive and on antiretroviral therapy. This will have important implications as universal antenatal haemoglobinopathy screening becomes more widespread, and as the number of HIV positive women of childbearing age increases.

Adult↗
PubMed2005

Acute stroke care in an Irish general hospital.

A majority of in-patients with acute stroke in Ireland are cared for by general physicians. We studied the process of care and outcomes of stroke patients admitted to an acute general hospital in a rural setting. Ninety-five patients (55 males and 40 females) were admitted over 36 weeks. A majority of patients had a CT brain scan (97%) and were assessed by the multidisciplinary team (59-70%). The mean length of stay was 16.6 days. In patient mortality was 18.9%. The commonest discharge destination was to the Medical Rehabilitation Unit (44%). A high prevalence of cardiovascular risk factors was identified indicating significant potential for secondary prevention.

Acute Disease↗
PubMed2004

Atomically resolved spin-dependent tunneling on the oxygen-terminated Fe3O4(111).

We employ spin-polarized STM to study the spin-dependent tunneling between a magnetite (111) sample and an antiferromagnetic tip through a vacuum barrier at room temperature. Atomic scale STM images show significant magnetic contrast corresponding to variations in the local surface states induced by oxygen vacancies. The estimated variations in tunneling magnetoresistance of 250% suggest that the spin-transport properties are significantly altered locally by the presence of surface defects.

Journal Article↗
PubMed2004

Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection.

The histological grade of 340 cutaneous mast cell tumours derived from 280 dogs was determined by an established histological grading system; 87 of the tumours (26 per cent) were well differentiated, 199 (59 per cent) were intermediately differentiated and 54 (16 per cent) were poorly differentiated. The one-year survival rates for the dogs with tumours of these three grades were significantly different (P = 0.0001), being 100 per cent, 92 per cent and 46 per cent, respectively. The median survival time for the dogs with poorly differentiated tumours was 278 days, significantly shorter than that for the dogs with either intermediately or well-differentiated tumours, which were both over 1300 days. Regrowth of the tumours was identified in 10 (19 per cent) of the dogs with poorly differentiated tumours, 12 (6 per cent) of the dogs with intermediately differentiated tumours and one of the dogs with well-differentiated tumours; only three of the tumours which regrew had initially had complete margins. The results suggest that wide surgical margins are not a prerequisite for a successful long-term outcome in dogs with well-differentiated cutaneous mast cell tumours.

Animals↗