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Biomedical subjects

P Lord

Publications and source records attributed to P Lord.

At least 19 recordsLinked to original sources
PubMed2006

Protein classification using ontology classification.

MOTIVATION: The classification of proteins expressed by an organism is an important step in understanding the molecular biology of that organism. Traditionally, this classification has been performed by human experts. Human knowledge can recognise the functional properties that are sufficient to place an individual gene product into a particular protein family group. Automation of this task usually fails to meet the 'gold standard' of the human annotator because of the difficult recognition stage. The growing number of genomes, the rapid changes in knowledge and the central role of classification in the annotation process, however, motivates the need to automate this process. RESULTS: We capture human understanding of how to recognise members of the protein phosphatases family by domain architecture as an ontology. By describing protein instances in terms of the domains they contain, it is possible to use description logic reasoners and our ontology to assign those proteins to a protein family class. We have tested our system on classifying the protein phosphatases of the human and Aspergillus fumigatus genomes and found that our knowledge-based, automatic classification matches, and sometimes surpasses, that of the human annotators. We have made the classification process fast and reproducible and, where appropriate knowledge is available, the method can potentially be generalised for use with any protein family. AVAILABILITY: All components described in this paper are freely available. OWL ontology http://www.bioinf.man.ac.uk/phosphabase myGrid http://www.mygrid.org.uk Instance Store http://instancestore.man.ac.uk.

Algorithms↗
PubMed2004

High detail radiography and histology of the centrodistal tarsal joint of Icelandic horses age 6 months to 6 years.

REASONS FOR PERFORMING STUDY: Osteoarthrosis (OA) in the distal tarsal joints, bone spavin, is a well known condition which is common in Icelandic horses age 6-12 years. OBJECTIVES: To determine the nature, location and age of appearance of early radiographic and histological changes in the centrodistal tarsal joint (CD) of young Icelandic horses. METHODS: Slab sections from the CD of young Icelandic horses were examined by high detail radiography (age 6 months to 6 years, n = 111) and histology (age 6 months to 4 years, n = 82) to detect and describe the early changes indicative of OA. Horses younger than 5 years were unridden. RESULTS: Chondronecrotic lesions histologically similar to those described in the early pathogenesis of OA were seen in 33% of the joints, located both medially and laterally. Radiographic sclerosis of the subchondral bone was recorded in 60% of the specimens, most often medially. Medial location was not associated with chondronecrosis, but was strongly related to age. Sclerosis was an infrequent finding on the lateral side, and was probably secondary to chondronecrosis in the corresponding part of the joint. Small defects in the subchondral bone were considered to be the most specific radiographic sign of OA as they were strongly associated with chondronecrosis. CONCLUSIONS: The high prevalence of chondronecrosis in the young horses indicates an early onset and slow progression of the disease. The early appearance also shows that the initiation of the disease is unrelated to the use of horses for riding. As clinical manifestation of OA in the distal tarsal joints is most often described in mature or old horses, the first stages of the disease are not likely to result in clinical signs. Subchondral bone sclerosis did not appear to be a primary factor in the development of OA in the CD but was considered to reflect an uneven distribution of biomechanical forces within the joint. POTENTIAL RELEVANCE: The development of OA in the CD of young Icelandic horses seems to be due to poor conformation or joint architecture rather than trauma or overloading. These aetiological factors are likely to be of importance for OA in the distal tarsal joints in other breeds as well. The influence of hindlimb conformation and the architecture of the distal tarsal joints on the biomechanics of joints need to be investigated, preferably by locomotion analysis in young horses.

Age Factors↗
PubMed2004

Relationship between scintigraphic and radiographic evaluations of spinous processes in the thoracolumbar spine in riding horses without clinical signs of back problems.

REASONS FOR PERFORMING STUDY: Radiography and scintigraphy are used to aid diagnosis of the cause of back pain, but a large variation in appearance and radiopharmaceutical uptake in fully functioning horses make diagnosis difficult. OBJECTIVES: To describe the range of and compare scintigraphic and radiographic findings in the spinous processes of horses without clinical signs of back problems. METHODS: Thirty-three apparently normal riding horses underwent scintigraphic and radiographic examinations of the spinous processes in the thoracolumbar spine. Scintigraphic images were evaluated in a continuous blue, green and red colour scale, and the level of radiopharmaceutical uptake in the spinous processes from T10-L2 was graded into none, mild, moderate or severe increased radiopharmaceutical uptake. Structural changes along the borders of the spinous processes and the width of the interspinous spaces from T10-L2 were recorded. RESULTS: Only 7 horses had no scintigraphic or radiographic findings. Nine horses had no increased radiopharmaceutical uptake, 17 had no sclerosis, 21 had no radiolucencies and 11 had normal spacing of the spinous processes (>4 mm wide). The majority of findings in 26 horses were located from T13-18 and were mild. CONCLUSIONS: The findings of a wide spectrum of scintigraphic and radiographic changes leads to the conclusion that changes within this range found in affected horses cannot be interpreted as clinically significant. POTENTIAL RELEVANCE: To determine whether scintigraphy and/or radiography can be used to separate horses with back pain from horses without clinical signs, the results from this study should be compared to the scintigraphic and radiographic findings in horses with clinical signs.

Analysis of Variance↗
PubMed2003

Day-to-day variability in glomerular filtration rate in normal dogs by scintigraphic technique.

The sources of variability in variability of scintigraphic measurements of glomerular filtration rate (GFR) have not been determined. The day to day variability of GFR was studied in 18 healthy beagle dogs. The renal uptake of 99mTc-diethylenetriaminepentaacetic acid (DTPA) of each dog was measured using a scintigraphic technique three times at intervals of 5-26 days. GFR was calculated from a regression equation relating uptake to plasma clearance, derived in our laboratory. The mean GFR was 3.97 +/- 0.72 (SD) ml/min/kg with values from 2.66 to 5.67 ml/min/kg. Analysis of variance (ANOVA) using a linear mixed model showed that most variability is a result of the dogs, less because of day to day variability and very little to the measurement variability. The repeatability coefficients for the day to day variability and measurement variability were 1.06 and 0.21 ml/min/kg respectively. The day to day variability can be caused by physiological homeostatic adjustments by the kidneys needed because of fluctuations in food and fluid intake, each dog's individual capacity to adjust, and to intrinsic errors in the measurement method. These results should be considered when using the scintigraphic method for clinical evaluation and research.

Animals↗
PubMed2003

Culling rate of Icelandic horses due to bone spavin.

A survival analysis was used to compare the culling rate of Icelandic horses due to the presence of radiographic and clinical signs of bone spavin. A follow-up study of 508 horses from a survey five years earlier was performed. In the original survey 46% of the horses had radiographic signs of bone spavin (RS) and/or lameness after flexion test of the tarsus. The horse owners were interviewed by telephone. The owners were asked if the horses were still used for riding and if not, they were regarded as culled. The owners were then asked when and why the horses were culled. During the 5 years, 98 horses had been culled, 151 had been withdrawn (sold or selected for breeding) and 259 were still used for riding. Hind limb lameness (HLL) was the most common reason for culling (n = 42). The rate of culling was low up to the age of II years, when it rose to 0.05 for horses with RS. The risk ratio for culling was twice as high for horses with RS compared with horses without RS and 5.5 times higher for culling because of HLL. The risk of culling (prognostic value) was highest for the combination of RS with lameness after flexion test, next highest for RS and lowest for lameness after flexion test as the only finding. It was concluded that bone spavin affects the duration of use of Icelandic horses and is the most common cause of culling due to disease of riding horses in the age range of 7-17 years.

Animals↗
PubMed2002

Differential gene expression in rats following subacute exposure to the anticonvulsant sodium valproate.

Sodium valproate (VPA) is clinically employed as an anticonvulsant and, to a lesser extent, as a mood stabilizer. While the incidence of toxicity associated with the clinical use of valproate is low, serious hepatotoxicity makes up a significant percentage of these rare adverse effects, with fatalities occurring mainly in children receiving polypharmacy. Previous studies have highlighted the different pharmacological effects of acute valproate exposure, a combination of which are likely to underpin its observed broad-spectrum anticonvulsant efficacy. However, limited studies have been undertaken to investigate the subacute effects of this compound and how genomic effects may underlie the observed hepatotoxic effects. Investigation into the mild hepatoxicity observed in rats exposed to high doses of VPA may provide important information on the human situation. Male Sprague-Dawley rats were dosed with 500 mg/kg/day sodium valproate: after necropsy, mRNA was subjected to suppression PCR subtractive hybridization, identifying 8 up-regulated and 14 down-regulated mRNA species. The down-regulation of several mRNA species coding for enzymes involved in cellular energetics (e.g., succinate dehydrogenase, aldolase B) was of particular interest, as mitochondrial dysfunction is a key feature of valproate hepatotoxicity. In vitro studies were then undertaken to examine the dose and time dependence of these changes and also their effect on the overall energy levels within the cell. We demonstrate that, both in vivo and in vitro, valproate exposure in rats results in a significant decrease in pathways involved in cellular energy homeostasis. These changes may provide insight into the rare human hepatoxicity associated with this compound.

Animals↗
PubMed2001

Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitis.

OBJECTIVES: There is a lack of information on the natural history of patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). However, cryptogenic fibrosing alveolitis (CFA) is known to have a poor long-term prognosis. As part of a longitudinal prospective study, we compared baseline characteristics in 18 patients with RA-ILD and 18 patients with CFA matched for age, sex and symptoms. We wished to establish whether there were significant baseline differences in clinical, physiological or radiological parameters. METHODS: A diagnosis of ILD was confirmed by high-resolution computed tomography (HRCT) and supported by clinical and physiological findings in all patients. A number of clinical, immunological, physiological and radiological parameters were compared between the two groups. The median age in each group was 77 yr and 10 patients in each group were male. RESULTS: Twelve of the RA patients had smoked in excess of 10 pack yr as compared with nine patients with CFA (not significant). Clubbing was found in five patients with RA-ILD and in 14 with CFA (P=0.008). Pulmonary function tests showed no significant differences between the groups in forced expiratory volume in 1s, vital capacity or gas transfer factor. HRCT showed more ground glass shadowing and peripheral disease in RA patients, but more established basal disease in those with CFA. Additionally, HRCT evidence of honeycombing was associated with an absence of rheumatoid factor and a low gas transfer factor. CONCLUSIONS: Clubbing is more common in patients with CFA, while RA-ILD patients have a higher prevalence of rheumatoid factor. Together with the differences in baseline HRCT, these variables in two groups of patients with similar physiological impairment at baseline may be important predictors of outcome in the longer term.

Aged↗
PubMed1999

Semi-quantitative assessment of tibial blood flow and distribution in response to surgical intervention using first pass radionuclide angiography and intravascular vital dye.

The acute vascular response in bone to surgical trauma was investigated utilizing a sheep model. Blood flow and distribution were determined using two methods; perfusion of the vasculature with an intravascular vital dye (Disulphine blue) prior to euthanasia and by radionuclide angiography (RNA) before and after each surgical intervention. The pattern of Disulphine blue distribution provided a good indication of local perfusion and response to surgical trauma (drilling holes). Radionuclide angiography provided a dynamic image of the vascular response to surgical trauma. The generation of time activity curves of the first pass of radionuclide bolus enabled calculation of the relative blood flow through selected regions. For both techniques areas of ischaemia were apparent which were directly related to the location of screw holes. We conclude that factors other than bone plate contact influence the ischaemia that develops in bone subsequent to the application of bone plates.

Animals↗
PubMed1997

Changes in protein and mRNA levels of growth factor/growth factor receptors in rat livers after administration of phenobarbitone or methylclofenapate.

The effects of phenobarbitone and methylclofenapate were studied on the expression of growth factor and growth factor receptors in livers of male Wistar rats. The major findings were: (1) a significant reduction in epidermal growth factor receptor (EGFR) protein observed with both treatments, and (2) levels of EGFR transcripts were only slightly decreased with both compounds. The reduction in the receptor level therefore does not occur via regulation of transcription. Mannose-6-phosphate receptors (M6PR, also called insulin-like growth factor II receptor) and M6PR transcripts remained unchanged in both experimental groups. Hepatocyte growth factor receptor (HGFR) transcripts were also unchanged in both experimental groups. Transcript levels of transforming growth factor-beta 1 (TGF-beta 1) were lower in both treatment groups compared with the control; the reduction was significant in the methylclofenapate group. This may have relevance to the finding by others that nafenopin, another peroxisome proliferator, suppresses rat hepatocyte apoptosis. Another finding of general interest was that the three "housekeeping genes", namely albumin, actin and glyceraldehyde-3-phosphate dehydrogenase, were influenced by both treatments thus limiting their use as controls for gel loading. The adaptation of a growth regulatory mechanism via EGFR and its ligands may provide conditions such that cells with aberrant growth control have a selective growth advantage over normal cells thus promoting tumorigenesis.

Animals↗
PubMed1986

Informed consent.

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Informed Consent↗