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Biomedical subjects

R G Cooper

Publications and source records attributed to R G Cooper.

At least 19 recordsLinked to original sources
PubMed2006

Monocyte chemotactic protein-1 single nucleotide polymorphisms do not confer susceptibility for the development of adult onset polymyositis/dermatomyositis in UK Caucasians.

OBJECTIVES: Polymyositis (PM) and dermatomyositis (DM) form part of the idiopathic inflammatory myopathies (IIMs). The chemokine monocyte chemotactic protein-1 (MCP-1) is expressed at sites of the T cell inflammatory response in the IIMs. We thus investigate whether genetic markers in the MCP-1 gene confer disease susceptibility for the development of PM and DM. METHODS: DNA samples were analysed from a group of 195 UK Caucasian IIM patients, comprising 103 PM and 92 DM. Their results were compared with those of 162 ethnically matched controls. The polymorphic positions of three single nucleotide polymorphisms (SNPs) and one insertion-deletion sequence within regions coding for MCP-1 were tested. The SNPs examined were located in intron 1 (rs2857657, C/G), exon 2 (rs4586, A/G) and the 3 ' untranslated region (rs13900, C/T). The insertion-deletion sequence was located in intron 1 (rs3917887, AGCTCCTCCTTCTC/-). Each SNP was tested for Hardy-Weinberg equilibrium and allelic/genotypic associations. Haplotype frequencies were estimated using the Expectation/Maximization algorithm. RESULTS: There was strong linkage disequilibrium present between three out of these four markers. The majority of controls were in Hardy Weinberg equilibrium. No allelic, genotypic or haplotypic associations were detected when comparing PM or DM cases to controls, or when PM and DM were compared with each other. CONCLUSIONS: Genetic markers in the MCP-1 gene do not demonstrate significant genetic associations with the IIMs, and do not discriminate PM from DM in a UK Caucasian population.

Adolescent↗
PubMed2006

The presence of quill mites (Gabucinia bicaudata) and lice (Struthiolipeurus struthionis) in ostrich wing feathers.

Quill mites (Gabucinia bicaudata) and lice (Struthiolipeurus struthionis) may infest ostrich feathers, resulting in skin damage, pruritus and excessive feather preening and loss. Four different feather types (prime white, femina extra wide, femina class 1, and femina short; n = 10) were collected. The quill mites and lice were removed with fine forceps, studied using a photographic optical microscope and counted microscopically at x 100 magnification following collection by sedimentation. They were placed in separate Petri dishes containing lactophenol solution and examined (x40 magnification). Anatomical features are described. The density of quill mites in all feather types of both wings was higher than that of the lice. There was no significant difference between the counts of both arthropods on the left wing and the right wing, respectively, except for the femina class 1 quill mites (P = 0.01). The femina extra wide feathers were a preferred habitat in both wings. Large standard deviations (quill mites left wing: 73 +/- 8; quill mites right wing: 69 +/- 7) suggested variations in the degree of migration between feather shafts or as a response to escape preening. It is recommended that ostriches be treated with an oral preparation of Ivermectin administered per os at a dosage rate of 0.2 mg/kg at 30-day intervals for quill mites, and with a 1-5 % Malathion dust at 14-day intervals for lice.

Animals↗
PubMed2004

Ostrich nutrition: a review from a Zimbabwean perspective.

The ostrich is an important animal in many livestock industries and, in the developing world, the export of meat and skins is a valuable source of foreign currency. As the successful growth and reproductive performance of ostriches depends on good nutrition it is extremely important to provide the correct diet. Some researchers have incorrectly assumed that poultry diets are useful for ostriches, but the vitamin and mineral requirements of these birds are unique and their diets should never be substituted with poultry or other livestock feeds. Producers should be knowledgeable about how different ingredients provide the essential nutrients for growth and development. Adequate nutrition is key to good flock performance and more research into ostrich nutrition is required. In Zimbabwe, one of the greatest costs involved in the keep of ostrich breeder birds is purchased feed, which can cost approximately US$ 4,555 for every 10 birds per annum. In order to cover these costs, the producer needs to ensure an adequate supply of birds for slaughter.

Animal Feed↗
PubMed2002

Quarts out of pint pots -- expanding the pint. Clinical budgeting in practice.

Clinical budgeting is the process whereby clinical users are charged for the resources they use. A system for recharging users for the costs of tests was introduced at the Northern General Hospital, Sheffield, in 1995, and has been in operation since. The system has allowed pathology to maintain budgetary balance, has automatically compensated for workload increases, has allowed the introduction of new tests, and has encouraged clinical users to include pathology costs in their bids for funding for clinical developments. The system works according to rules agreed between pathology and its users at the outset, but once set up takes a minimal amount of work to operate and maintain.

Budgets↗
PubMed2001

Paraspinal muscle EMG fatigue testing with two methods in healthy volunteers. Reliability in the context of clinical applications.

OBJECTIVE: Comparison of the accuracy of surface electromyogram for back muscle endurance assessment with two different tests. DESIGN: Test-retest measurements in 16 healthy volunteers on two separate occasions for each test under controlled conditions. BACKGROUND: Back muscle endurance is considered important in low back pain rehabilitation. Reliability of paraspinal muscle endurance assessment is a pre-requisite for accurate and meaningful clinical applications of the technique. METHODS: All participants performed each test twice. A direct comparison was made between two popular fatigue testing methods, the modified Biering-Sørensen and a 60% maximum voluntary isometric contraction in the upright position during which time fatigue was assessed from the electromyogram spectral and amplitude analysis. RESULTS: Reproducibility of initial median frequency was excellent for both tests. Normalised median frequency slope values were more reliable with the 60% maximum voluntary contraction upright test. The clinical applicability of these measures in detecting significant differences after patient rehabilitation is recommended. Root mean square had very large between-day error for both tests.

Adult↗
PubMed2000

Renal electrolyte and fluid handling in the rat following chloroquine and/or ethanol administration.

We postulated that chloroquine and/or ethanol affect plasma arginine vasopressin (AVP) concentrations to alter renal function. Therefore, we studied the effects of chloroquine and/or ethanol on plasma AVP concentrations and fluid, urinary Na(+) and K(+) outputs in separate groups of anaesthetized Sprague-Dawley (SD) rats challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl.min(-1). After a 3-h equilibration period, vehicle, chloroquine (0.06 microg. min(-1)), ethanol (2.4 or 24 microg.min(-1)) or both chloroquine and ethanol were added to the infusate after 1 h (control) for 1 h 20 min (treatment). The animals were switched back to the infusate alone for the final 1 h 40 min recovery periods. Urine flow Na(+) and K(+) excretion rates were determined at 20-min intervals over the subsequent 4-h postequilibration period. Blood was collected from separate groups of animals at the end of treatment period or equivalent time for control animals for measurement of plasma aldosterone and AVP concentrations by radioimmunoassay. Simultaneous chloroquine and ethanol infusion significantly (p < 0.01) increased plasma chloroquine concentrations in an ethanol dose-dependent manner by comparison with animals administered chloroquine alone. Chloroquine infusion alone (0.06 microg.min(-1)) and/or ethanol (2.4 or 24 microg.min(-1)) elevated plasma AVP concentrations from 9.73 +/- 1.64 fmol.l(-1) in control rats to 15.65 +/- 2.49 fmol.l(-1), 17. 39 +/- 4.21 fmol.l(-1), and 33.87 +/- 6.18 fmol.l(-1), respectively. Separate administration of chloroquine or ethanol at low dose rates increased urinary Na(+) excretion rates. We conclude that the impairment of renal electrolyte handling associated with chloroquine administration may be exacerbated by ethanol.

Animals↗
PubMed2000

Effects of ethanol on the changes in renal fluid and electrolyte handling and kidney morphology induced by long-term chloroquine administration to rats.

This study investigated the effects of long-term chloroquine and ethanol administration on renal fluid and electrolyte handling and kidney structure. Male Sprague-Dawley rats were orally administered with chloroquine diphosphate (20 microg kg(-1) bw) and/or ethanol (1.6 g kg(-1) bw) every third consecutive day for 4 weeks. Urine volume and total urinary outputs of Na+ and K+ were determined from 24-h samples. For detailed renal studies, rats were subsequently anaesthetised and challenged with a continuous jugular infusion of 0.077 M NaCl at 150 microl min(-1) 24 h after the last treatment. After a 3-h equilibration period, urine flow, Na+ and K+ excretion rates were determined over a 4-h period. Plasma concentrations of AVP and aldosterone were measured in unanaesthetised rats and in anaesthetised rats after hypotonic saline infusion. In separate groups, the rats were anaesthetised with an overdose of ether after 4 weeks of treatment and part of the right kidney was quickly collected and routinely processed for light microscopy. Chloroquine decreased Na+ excretion and increased plasma aldosterone concentrations in anaesthetised rats. Ethanol alone did not alter urinary Na+ outputs or aldosterone levels. Combined chloroquine and ethanol increased renal Na+ excretion, but did not affect plasma aldosterone levels. In unanaesthetised animals all treatments increased aldosterone levels by comparison with control rats. Urinary Na+ excretion was decreased by separate administration of either chloroquine or ethanol, but increased by combined treatment. Microscopic studies showed that concurrent chloroquine and ethanol administration induced extensive damage of the proximal tubule and collecting ducts cells. The results of this study suggest that alcohol consumption and chloroquine administration could result in diminished renal function possibly due to alteration of renally active hormones or kidney morphology.

Aldosterone↗
PubMed2000

Cell delivery, intracellular trafficking and expression of an integrin-mediated gene transfer vector in tracheal epithelial cells.

The mechanism of cell entry and intracellular fate of a gene transfer vector composed of a receptor-targeting, DNA-condensing peptide, RGD-oligolysine, a luciferase encoding plasmid DNA (pDNA) and a cationic liposome was examined. We demonstrate by confocal microscopy, electron microscopy and subcellular fractionation that the major mechanism of entry of the vector is endocytic. The vector complex rapidly (5 min) internalizes into early endosomes, then late endosomes and lysosomes. Entry involves, at least in part, clathrin-coated pit-mediated endocytosis since different conditions or drugs known to influence this pathway modify both uptake of pDNA and its expression. The observed increase in expression with addition of a lip some correlated with an increase in the rate of transfer of the pDNA to lysosomes, a decrease in intracellular recycling and exocytosis of the pDNA and an increase in the amount of pDNA in the nuclear fraction. Trafficking within the cell involved endosome fusion and the acid environment of the endosomes-lysosomes was beneficial for expression. After 30 min both the peptide and pDNA localized to the nucleus and the amount of intact pDNA in the nuclear fraction was highest with liposome and peptide. A better understanding of the cellular mechanisms by which vectors transfer to and traffic in cells should help design improved vectors.

Cation Exchange Resins↗
PubMed2000

Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery.

A novel formulation of cationic liposomes containing the novel cytofectin ACHx was used for delivery of an anti-inflammatory cytokine gene, IL-10, to mice with established collagen induced arthritis. A single intraperitoneal injection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and prolonged amelioration of arthritis for 30 days. Preliminary experiments suggested that the therapeutic effect was IL-10 dose-dependent. The distribution of the human IL-10 DNA after injection was widespread, including the inflamed paws. Human IL-10 mRNA was also detected in the paws 24 h after injection. IL-10 protein was below the level of detection in paws and serum but was detected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for anti-inflammatory treatment of arthritis.

Animals↗
PubMed2000

Effects of ethanol on plasma chloroquine, arginine vasopressin (AVP) concentrations and renal hydro-electrolyte handling in the rat.

Current evidence in literature suggests that acute effects of either chloroquine or ethanol on kidney function partly depend on influencing plasma concentrations of arginine vasopressin (AVP). Therefore, the goal of the current study was to explore the effects of chloroquine and/or various doses of ethanol on plasma AVP levels and associated effects on renal hydro-electrolyte handling. Separate groups of male anaesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 microL/min(-1). After 3 h equilibration period, consecutive 20 min urine collections were made over the subsequent 4 h of 1 h control, 1 h 20 min treatment and 1 h 40 min postequilibration periods for measurements of urine flow and Na+ and K+ excretion rates. Chloroquine (0.06 microg/min(-1)) and/or ethanol at either 2.4, 6, 18 or 24 microg/min(-1) were added to the infusate during the treatment period. Trunk blood was collected after the treatment period from parallel groups for AVP, ethanol and chloroquine measurements. Vehicle infused animals acted as control animals. Infusion of ethanol at low rate of 2.4 microg/min(-1) increased Na+ excretion rates, but high rates (6-24 microg/min(-1)) did not elicit such effects. Plasma ethanol concentrations were undetectable following administration of ethanol alone at 2.4 or 6 microg/min(-1). However, ethanols were measurable following co-infusion of chloroquine and ethanol at 6 microg/min(-1) (6+/-1 mg/dL(-1)). Concurrent chloroquine and ethanol (24 microg/min(-1)) administration elevated plasma ethanol concentrations by 26% by comparison with that of ethanol alone at the same dose. Chloroquine and ethanol infusion at all doses significantly (p < 0.01) increased plasma chloroquine concentrations. Intravenous infusion of ethanol increased plasma AVP concentrations in a dose-dependent manner. The observations of this study suggest that acute ethanol increases plasma AVP levels in a dose-dependent manner to affect hydro-electrolyte balance.

Animals↗
PubMed1999

Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation.

The Raf family of serine/threonine protein kinases couple growth factor receptor stimulation to mitogen activated protein kinase activation, but their own regulation is poorly understood. Using phospho-specific antisera, we show that activated Raf-1 is phosphorylated on S338 and Y341. Expression of Raf-1 with oncogenic Ras gives predominantly S338 phosphorylation, whereas activated Src gives predominantly Y341 phosphorylation. Phosphorylation at both sites is maximal only when both oncogenic Ras and activated Src are present. Raf-1 that cannot interact with Ras-GTP is not phosphorylated, showing that phosphorylation is Ras dependent, presumably occurring at the plasma membrane. Mutations which prevent phosphorylation at either site block Raf-1 activation and maximal activity is seen only when both are phosphorylated. Mutations at S339 or Y340 do not block Raf-1 activation. While B-Raf lacks a tyrosine phosphorylation site equivalent to Y341 of Raf-1, S445 of B-Raf is equivalent to S338 of Raf-1. Phosphorylation of S445 is constitutive and is not stimulated by oncogenic Ras. However, S445 phosphorylation still contributes to B-Raf activation by elevating basal and consequently Ras-stimulated activity. Thus, there are considerable differences between the activation of the Raf proteins; Ras-GTP mediates two phosphorylation events required for Raf-1 activation but does not regulate such events for B-Raf.

Animals↗
PubMed1999

Cationic liposome-mediated DNA transfection in organotypic explant cultures of the ventral mesencephalon.

We have examined the potential of cationic liposomes as a tool for approaches to gene therapy in the CNS. Our previous work has shown that cationic liposomes formulated from 3 beta-[N-(N',N'-dimethylaminoethane)carbamoyl] cholesterol (DC-Chol) and dioleoyl-L-alpha-phosphatidylethanolamine (DOPE) could achieve high transfection levels in a neuronal cell line (McQuillin et al. Neuroreport 1997; 8: 1481-1484). We therefore wished to assess transfection efficiencies in organotypic cultures from the brain with a reporter plasmid expressing E. coli beta-galactosidase in order to mimic an in vivo model. Explant cultures were generated according to the method of Stoppini et al (J Neurosci Meth 1991; 37: 173-182) with slight modifications. Brain slices were maintained on transparent porous membranes and were observed to maintain their intrinsic connectivity and cytoarchitecture to a large degree over periods of up to 6 weeks in culture. CNS tissue was obtained from rats at birth or 5 days after birth. After transfection beta-galactosidase expression was detected in cells of both neuronal and non-neuronal morphology. Control cultures were exposed to liposome alone and a plasmid that had the beta-galactosidase gene insert removed. Only low levels of endogenous beta-galactosidase reactivity were seen in these control cultures. DC-Chol/DOPE-mediated transfection was confirmed using a RT-PCR protocol capable of differentiating between untranscribed plasmid DNA and RNA generated from the transfected vector. These results suggest that cationic liposomes, particularly DC-Chol/DOPE liposomes, will be useful as delivery agents for gene transfer to CNS cells in vitro and possibly in vivo.

Animals↗
PubMed1999

Predicting 'normal' grip strength for rheumatoid arthritis patients.

OBJECTIVE: An ability to predict accurately 'normal' grip strength in rheumatoid arthritis (RA) patients would facilitate a more accurate assessment of the degree of their functional loss. This, in turn, would allow the setting of more meaningful treatment goals aimed at restoring hand function towards normal. This study carefully measures three modalities of hand grip strength and their correlation with multiple simple anthropometric parameters in normal subjects. We aim to determine which of these parameters are best correlated to grip strength, and whether this correlation is strong enough to allow the accurate prediction of what normal grip strength should be in RA patients. METHODS: In 81 normal subjects (67 female), power, pinch and tripod grip strength measurements were made using an MIE digital pinch grip analyser. These strength data were correlated with specific local forearm anthropometric measurements: forearm circumference, forearm length, forearm volume, hand circumference, hand length, hand volume, hand and forearm volume, and various general anthropometric parameters (weight, height and age). These normal subjects had been chosen so as to be age and sex matched with 83 RA patients (67 female) in whom the same strength and anthropometric parameters were assessed and correlated. In patients, the grip strength results were additionally correlated with two markers of disease activity: a modified Ritchie Articular Index local to the hand and forearm (mRAI) and a visual analogue scale (VAS) assessing subjective pain severity. RESULTS: In normal subjects, clear correlations were demonstrated between hand grip strengths and all specific anthropometric variables, the strongest correlation being with forearm and hand volume (r = 0.729 and 0.638 for dominant and non-dominant hands, respectively; P < 0.01 for both). The patients were considerably weaker than normal subjects. Markers of disease activity showed a negative correlation with grip strength. In normal subjects, the dominant hand was significantly stronger than the non-dominant hand, and on average by 8%, while the opposite was true in patients, who were 20% weaker on the dominant side. CONCLUSION: Simple anthropometric measurements, and forearm and hand volume in particular, would be useful at baseline for predicting 'normal' hand grip strength in RA patients, both in the clinical setting and in research trials aimed at improving grip strength and hand function.

Aged↗
PubMed1999

Prediction of maximal back muscle strength from indices of body mass and fat-free body mass.

OBJECTIVES: The purpose of this study was to examine, in healthy volunteers, the relationship between back extensor muscle strength and body size. METHODS: The maximal voluntary isometric back extensor strength of 456 volunteers, aged 18-42 yr and with no history of low back pain, was measured in a standing, slightly flexed forward posture. This was then correlated with two indices of body size: body mass and fat-free body mass. RESULTS: Significant linear relationships were observed between back muscle strength and each of the two indices of body size. There was a gender difference in both the slope and the intercept of the regression equations describing the relationships. There was no independent influence of age within the range studied. CONCLUSION: It was possible to establish predictive equations for back extensor strength based on body size which could be used to quantify strength 'deficits', for instance in patients with low back pain, and to prescribe submaximal target forces for use in endurance training and testing.

Adult↗