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Biomedical subjects

J M Cooper

Publications and source records attributed to J M Cooper.

At least 19 recordsLinked to original sources
PubMed2006

The liquid-liquid diffusive extraction of hydrocarbons from a North Sea oil using a microfluidic format.

Extraction of a GC-amenable hydrocarbon fraction from oil by liquid-liquid diffusion across a laminar interface can be performed in a microfluidic format. Analysis of figures of merit, determined using standard analytical techniques, show this method to be an effective new tool for rapidly processing small quantities of oil and petroleum for GC analysis. Methods based upon similar microsystems devices could find widespread use in a variety of fields, including those associated with organic geochemistry and oil exploration and production, where the manipulation of petroleum constituents (greater than C14) is necessary for analytical purposes.

Journal Article↗
PubMed2006

Multipoint holographic optical velocimetry in microfluidic systems.

We show how holographic optical trapping can be used for the multipoint measurement of fluid flow in microscopic geometries. An array of microprobes can be simultaneously trapped and used to map out the fluid flow in a microfluidic device. The optical traps are alternately turned on and off such that the probe particles are displaced by the flow of the surrounding fluid and then retrapped. The particles' displacements are monitored by digital video microscopy and directly converted into velocity field values. This technique enables the measurement of a two-dimensional flow field at points arbitrarily distributed in a three-dimensional volume. The validity of the technique is demonstrated for the case of the flow around a spinning sphere and the flow at the outlet of a microchannel.

Journal Article↗
PubMed2006

In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the human gut microflora.

AIMS: To determine the fermentation profiles by human gut bacteria of arabino-oligosaccharides of varying degree of polymerization. MATERIALS AND METHODS: Sugar beet arabinan was hydrolyzed with a commercial pectinase and eight fractions, of varying molecular weight, were isolated by gel-filtration chromatography. Hydrolysis fractions, arabinose, arabinan and fructo-oligosaccharides were fermented anaerobically by gut bacteria. Total bacteria, bifidobacteria, bacteroides, lactobacilli and the Clostridium perfringens/histolyticum sub. grp. were enumerated using fluorescent in situ hybridization. RESULTS: Bifidobacteria were stimulated to different extents depending on molecular weight, i.e. maximum increase in bifidobacteria after 48 h was seen on the lower molecular weight fractions. Lactobacilli fluctuated depending on the initial inoculum levels. Bacteroides numbers varied according to fraction; arabinan, arabinose and higher oligosaccharides (degree of polymerization, dp > 8) resulted in significant increases at 24 h. Only carbohydrate mixtures with dp of 1-2 resulted in significant increases at 48 h (log 8.77 +/- 0.23). Clostridia decreased on all substrates. CONCLUSIONS: Arabino-oligosaccharides can be considered as potential prebiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Arabinan is widely available as it is a component of sugar beet pulp, a co-product from the sugar beet industry. Generation of prebiotic functionality from arabinan would represent significant added value to a renewable resource.

Arabinose↗
PubMed2005

Ultrasonographic assessment of the rate of solid-phase gastric emptying in dogs.

Twelve healthy dogs were used in an ultrasonographic assessment of the effect of the composition of a solid meal on the rate of gastric emptying. The dogs were fasted for nine hours before they were fed either a standard or a high energy density test meal, in a cross-over study design. The gastric antrum was visualised with a 6.5 MHz microconvex transducer, and the area inside the elliptical shape defined by the craniocaudal and ventrodorsal diameters of the stomach was measured. Antral images were acquired at regular intervals for six hours after the ingestion of the test meal. Three indices to describe the rate of gastric emptying were computed: the gastric half-emptying time (t1/2), the time to 50 per cent maximal antral area (t50%), and the time of maximal antral area (tmax). The values of t50% and t1/2 calculated for the high energy density meals were significantly longer than for the standard meals, but there was no significant difference between the tmax values.

Animal Feed↗
PubMed2004

Current and future uses of breath analysis as a diagnostic tool.

The analysis of exhaled breath is a potentially useful method for application in veterinary diagnostics. Breath samples can be easily collected from animals by means of a face mask or collection chamber with minimal disturbance to the animal. After the administration of a 13C-labelled compound the recovery of 13C in breath can be used to investigate gastrointestinal and digestive functions. Exhaled hydrogen can be used to assess orocaecal transit time and malabsorption, and exhaled nitric oxide, carbon monoxide and pentane can be used to assess oxidative stress and inflammation. The analysis of compounds dissolved in the aqueous phase of breath (the exhaled breath condensate) can be used to assess airway inflammation. This review summarises the current status of breath analysis in veterinary medicine, and analyses its potential for assessing animal health and disease.

Animals↗
PubMed2004

G209A mutant alpha synuclein expression specifically enhances dopamine induced oxidative damage.

Alpha synuclein protein may play an important role in familial and sporadic Parkinson's disease pathology. We have induced G209A mutant or wild-type alpha-synuclein expression in stable HEK293 cell models to determine if this influences markers of oxidative stress and damage under normal conditions or in the presence of dopamine or paraquat. Induced wild-type or mutant alpha-synuclein expression alone had no effect upon levels of oxidative stress or damage, as measured by glutathione levels or aconitase activity. Both wild-type and mutant alpha-synuclein expression decreased the oxidative damage induced by paraquat, although the protection was less marked with mutant alpha-synuclein expression. This suggests that alpha-synuclein expression may either have anti-oxidant properties or may upregulate cellular antioxidant levels, a function that was diminished by the G209A mutation. However, mutant but not wild-type alpha-synuclein expression specifically enhanced dopamine associated oxidative damage. Non-expressing cells treated with reserpine to inhibit the vesicular monoamine compartmentalisation produced similar results. However, consistent with the hypothesis that mutant alpha-synuclein disrupts vesicular dopamine compartmentalization, this effect was diminished in cells expressing mutant alpha-synuclein. This may result in increased dopamine metabolism and cause selective oxidative damage to dopaminergic cells.

Aconitate Hydratase↗
PubMed2004

Validation of a method for collection and assay of pentane in the exhaled breath of the horse.

Oxidative stress refers to an imbalance between the production of oxidising free radicals and the antioxidant defenses of the cell, and is associated with many pathogenic processes. Oxidative damage to cellular lipids results in the evolution of pentane and ethane gas, and detection of these hydrocarbons in the exhaled breath can be used to monitor in vivo oxidative stress. The aim of this study was to validate a gas chromatography (GC) method for measurement of breath pentane in the horse. The GC-system developed showed good specificity for discrimination of pentane from other breath hydrocarbons, and was sensitive to 0.5 ppb pentane. Pentane was detected in the exhaled breath of five horses investigated on two occasions. The results of this preliminary study demonstrate that breath pentane can be measured in the horse, and further work is now justified to investigate the feasibility of applying this method for monitoring in vivo oxidative stress in the horse.

Animals↗
PubMed2004

Role of oxidative damage in Friedreich's ataxia.

Plasma malondialdehyde (MDA) levels were raised in Friedreich's ataxia (FRDA) patients. These levels correlated with increasing age and disease duration, suggesting lipid peroxidation increased with disease progression. Using fibroblasts from FRDA patients we observed that GSH levels and aconitase activities were normal, suggesting their antioxidant status was unchanged. When exposed to various agents to increase free radical generation we observed that intracellular superoxide generation induced by paraquat caused enhanced oxidative damage. This correlated with the size of the GAA1 expansion, suggesting decreased frataxin levels may render the cells more vulnerable to mild oxidative stress. More severe oxidative stress induced by hydrogen peroxide caused increased cell death in FRDA fibroblasts but was not significantly different from control cells. We propose that abnormal respiratory chain function and iron accumulation may lead to a progressive increase in oxidative damage, but increased sensitivity to free radicals may not require detectable respiratory chain dysfunction.

Aconitate Hydratase↗
PubMed2003

Alpha-synuclein expression in HEK293 cells enhances the mitochondrial sensitivity to rotenone.

Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism is not clear. We have investigated the short term effect of G209A mutant or wild-type alpha-synuclein expression upon mitochondrial function using stable inducible cell models. Mitochondrial respiratory chain activities and membrane potential were normal suggesting that increased wild-type or mutant alpha-synuclein expression did not directly affect these parameters. However, both wild-type and mutant G209A alpha-synuclein expression enhanced the fall in mitochondrial membrane potential induced by the complex I inhibitor rotenone. This suggests an indirect interaction between alpha-synuclein expression and mitochondrial function which could render the mitochondria more vulnerable to inhibition by potential endogenous or exogenous factors found in dopaminergic neurones.

Cell Line↗
PubMed2003

Friedreich's Ataxia: disease mechanisms, antioxidant and Coenzyme Q10 therapy.

Mitochondria clearly play a central role in the pathogenesis of Friedreich's Ataxia. The most common genetic abnormality results in the deficiency of the protein frataxin, which is targeted to the mitochondrion. Research since this discovery has indicated that mitochondrial respiratory chain dysfunction, mitochondrial iron accumulation and oxidative damage are important components of the disease mechanism. While the role of frataxin is not known, evidence is currently pointing to a role in either mitochondrial iron handling or iron sulphur centre synthesis. These advances in our understanding of the disease mechanisms are enabling therapeutic avenues to be explored, in particular the use of established drugs such as antioxidants and enhancers of respiratory chain function. Vitamin E therapy has been shown to be beneficial in patients with ataxia with vitamin E deficiency, and CoQ10 therapy was effective in some patients with ataxia associated with CoQ10 deficiency. A combined therapy involving long term treatment with high doses of vitamin E and coenzyme Q10 has jointly targeted two of the major features of Friedreich's Ataxia; decreased mitochondrial respiratory chain function and increased oxidative stress. This therapy clearly showed a rapid and sustained increase in the energy generated by the FRDA heart muscle, nearly returning to normal levels. The improvements in skeletal muscle energy generation parallel those of the heart but to a lower level. While this therapy appeared to slow the predicted progression of some clinical symptoms a larger placebo controlled study is required to confirm these observations. Other antioxidant strategies have involved the use of Idebenone, selenium and N acetyl cysteine but only the use of Idebenone has involved structured trials with relatively large patient numbers. Idebenone clearly had an impact upon the cardiac hypertrophy in the majority of patients, although there have not been any other significant benefits reported to date.

Antioxidants↗
PubMed2003

A comparison of the rate of recovery of 13CO2 in exhaled breath with 2H in body water following ingestion of [2H/13C]octanoic acid in a dog.

The objective of this study was to assess post-gastric processing of octanoic acid (OA) by comparing the rate of recovery of 13C in breath with the rate of recovery of 2H in saliva following ingestion of [2H/13C]OA. A test meal with 100mg [13C]OA and 750 mg [2H]OA was ingested on two separate occasions by one dog. Exhaled breath and saliva samples were collected at set time points for 6h following ingestion of the test meal. Two indices were computed, half recovery time (t(1/2)) and the time of peak excretion (t(max)). Recovery of 2H in saliva was quicker than recovery of 13C in breath as determined by the difference in the indices for each isotope; 1.33 and 1.59 h for t(1/2) and t(max), respectively. These findings suggest that the post-gastric processing of OA imposes a delay on the recovery of 13C in breath in the dog, as occurs in man and in the horse.

Animals↗
PubMed2003

Inclusion formation in Huntington's disease R6/2 mouse muscle cultures.

Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion in the number of glutamine repeats in the N-terminal region of the huntingtin protein. Nuclear and cytoplasmic aggregates of the N-terminal portion of huntingtin have been found in the brains of HD patients and the brains and non-neuronal tissues of the R6/2 HD transgenic mouse. We have cultured myoblasts and myotubes from transgenic R6/2 mice and littermate controls to investigate the formation of these inclusions in post mitotic cells. Huntingtin immunoreactivity was intense in differentiating, desmin positive myoblasts and myotubes from both control and R6/2 mice suggesting that it may play a role in myotube differentiation. Following differentiation huntingtin and ubiquitin positive aggregates were observed in R6/2 but not control cultures. After 3 weeks in differentiation medium cytoplasmic huntingtin and ubiquitin immunoreactive aggregates were observed in non-myotube cells, while nuclear huntingtin aggregates were seen in a proportion of myotubes after 6 weeks. Growth in the absence of serum resulted in a marked increase in the number of R6/2 myotubes containing nuclear inclusions after 6 weeks demonstrating that environmental factors influenced huntingtin aggregate formation in these cells. Consequently, cultured myotubes from R6/2 mice may be a useful post mitotic cell culture model to study both the biochemical consequences of huntingtin aggregates and the factors that may influence aggregate formation.

Animals↗
PubMed2002

High-throughput screens for postgenomics: studies of protein crystallization using microsystems technology.

This paper describes the fabrication of a micromachined miniaturized array of chambers in a 2-mm-thick single crystal (100) silicon substrate for the combinatorial screening of the conditions required for protein crystallization screening (including both temperature and the concentration of crystallization agent). The device was fabricated using standard photolithography techniques, reactive ion etching (RIE) and anisotropic silicon wet etching to produce an array of 10 x 10 microchambers, with each element having a volume of 5 microL. A custom-built temperature controller was used to drive two peltier elements in order to maintain a temperature gradient (between 12 and 40 degrees C) across the device. The performance of the microsystem was illustrated by studying the crystallization of a model protein, hen egg white lysozyme. The crystals obtained were studied using X-ray diffraction at room temperature and exhibited 1.78 A resolution. The problems of delivering a robust crystallization protocol, including issues of device fabrication, delivery of a reproducible temperature gradient, and overcoming evaporation are described.

Crystallization↗
PubMed2002

Interconnected reversible lab-on-a-chip technology.

Interconnected lab-on-a-chip modules with minimal dead volume have been developed resulting in the 'plug and play' concept based upon a reversible bonding process. This paper describes the detail of a chip to chip interconnection method, where devices have been aligned and bonded within 15 min and rapidly disassembled in under 5 min. The transport of fluorescein between the chip modules was used as a model microfluidic system and analysed in order to demonstrate the electrophoretic performance of the device and the interconnected junction. Using this technology, in the future different modules for various applications can be developed and interconnected, depending on the required applications. In addition, this simple but rapid method of chip to chip connection overcomes potential problems associated with integrating incompatible materials on one device.

Journal Article↗
PubMed2002

Miniaturized screening technologies for drug discovery.

Adaptive Profiling (APL) and other biochip companies aim to harness the power of microsystems technology together with advances in chemistry and molecular biology, to become service and technology providers to organizations involved in pharmaceutical research and development. By supplying a unique range of decision-making tools that aid an earlier identification of qualified drug candidates for clinical development, the company should gain a significant share of the 10 billion US dollar biological screening, bioavailability and toxicity assessment market.

Animals↗