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P Styles

Publications and source records attributed to P Styles.

At least 73 records · Page 4Linked to original sources
PubMed1995

Assessment of mitochondrial function and control in normal and diseased states.

Mitochondrial function in muscle in vivo can be quantitatively evaluated using 31-phosphorus nuclear magnetic resonance. In resting muscle, the concentrations of ions (e.g. H+, Na+) and two of the major bioenergetic components (inorganic phosphate and creatine) are determined by regulated transcellular transport processes. During recovery after exercise the kinetics and control of mitochondrial ATP synthesis can be established. During exercise the relative contributions to ATP synthesis of phosphocreatine (using creatine kinase), anaerobic glycogenolysis and oxidative phosphorylation are dissected and have been shown to change with time. The consequences of mitochondrial lesions and dysfunctions on these processes have been summarised.

Adenosine Triphosphate↗
PubMed1995

Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study.

Duchenne muscular dystrophy (DMD) is one of a range of muscular dystrophies caused by abnormalities of the short arm of the X chromosome (Xp21), which often cause mental retardation in addition to progressive muscular weakness. Normal dystrophin expression is lacking in both skeletal muscle and brain of affected subjects. Phosphorus-31 magnetic resonance spectroscopy has shown several abnormalities in skeletal muscle in DMD. We looked for similar abnormalities in brain in patients with DMD and related the findings to neuropsychological test results. We studied by magnetic resonance spectroscopy 19 boys (aged 76-167 months) diagnosed as having DMD and 19 control boys of similar age (87-135 months). Intelligence quotient (IQ) was assessed with the Wechsler Intelligence Scale for children. The DMD patients had significantly higher values than the controls in the brain ratios of inorganic phosphate to adenosine triphosphate (mean 0.53 [SD 0.21] vs 0.36 [0.09], p = 0.003), to phosphomonoesters (0.40 [0.07] vs 0.29 [0.07], p = 0.0001), and to phosphocreatine (0.44 [0.10] vs 0.37 [0.08], p = 0.02). There were significant differences between the DMD patients and the controls in full-scale IQ (76 [16] vs 101 [16], p = 0.0001), performance IQ (78 [17] vs 94 [14], p = 0.003), and verbal IQ (78 [17] vs 106 [17], p = 0.0001). These altered metabolite ratios parallel the findings in dystrophic muscle and suggest bioenergetic similarities in tissues that lack dystrophin.

Adenosine Triphosphate↗
PubMed1995

Incidence of persons with a learning disability detained in police custody. A needs assessment for service development.

The aim of this prospective study was to identify the number of people with a possible learning disability suspected of having committed a criminal offence who were taken into police custody during a defined period of time. Between 18 January 1993 and 18 March 1993 992 people were taken into custody at Parkside Police Station, Cambridge, of whom 251 (25.3%) were screened by the custody officer using a brief questionnaire to ascertain the presence or absence of reading and writing difficulties and to see if they had received extra help at school or if they had attended a special needs school. Information on age, sex, suspected offence, disposal, if a solicitor assisted and incidence of homelessness was gathered from the custody reports.

Adolescent↗
PubMed1994

Intracellular Ca2+ transients in isolated perfused rat heart: measurement using the fluorescent indicator Fura-2/AM.

We have investigated the nature of Fura-2/AM loading into isolated perfused rat heart and the temporal and kinetic relationship between left ventricular [Ca2+]i dependent fluorescence and isovolumic pressure. The contribution of hydrolysed mitochondrial matrix Fura-2 fluorescence to that measured from the surface of the heart was estimated to be 43.9 +/- 5.5% by the addition of 100 microM Mn2+ to the perfusate. Maximum endothelial Fura-2 fluorescence ratio, estimated by the addition of 3 microM bradykinin to the perfusate, was found to constitute 33.6 +/- 2.7% of the maximum myocardial Fura-2 fluorescence ratio. Approximately 11.2% of the 340 nm surface fluorescence was insensitive to 20 mM Mn2+ in the presence of ionomycin (3 microM) and therefore indicates the degree of partial hydrolysis of Fura-2/AM. Thus, depending on the contribution of endothelial Fura-2 fluorescence at a physiological endothelial calcium concentration, cytosolic fluorescence may comprise between 11-45% of the total cellular fluorescence at 340 nm. Net tissue interference of the Fura-2 fluorescence ratio by NADH emission and myoglobin absorption remained unaltered, providing the oxygenation state of the tissue was unaltered throughout the experiment. The [Ca2+]i dependent fluorescence decay from peak systole was best fitted to a biexponential decay with fast and slow rate constants of 18.08 +/- 1.97 s-1 and 0.23 +/- 0.02 s-1, respectively. In addition, a phase shift was observed between temporal and kinetic measurements of the left ventricular isovolumic pressure and calcium dependent fluorescence traces during a contraction-relaxation cycle. We conclude that despite imperfect Fura-2/AM loading, the temporal and kinetic characteristics of intracellular [Ca2+] transients in normal isolated perfused rat heart are similar to those reported in more controlled preparations such as isolated myocytes and cardiac trabeculae.

Animals↗
PubMed1994

Uraemic muscle metabolism at rest and during exercise.

The effect of chronic renal failure and the accompanying hyperphosphataemia on muscle metabolism at rest and during exercise was examined in a group of undialysed patients suffering from chronic renal failure. 31P magnetic resonance spectroscopy was used to measure intracellular high-energy phosphates in resting muscle as well as changes in the concentrations of these metabolites during exercise and recovery from exercise. In resting muscle, cell [Pi] rose with plasma [Pi], and free [ADP] changed such that the phosphorylation potential ([ATP]/([ADP] x [Pi])), which probably controls mitochondrial oxidation in resting muscle, was preserved despite a wide variation in cell [Pi]. The maximal oxidative capacity of the muscle was calculated from the kinetics of phosphocreatine recovery after exercise. There was no reduction in uraemic muscle oxidative capacity compared to control muscle. This contrasts with our finding of a reduction in the mitochondrial oxidative capacity in the muscle of patients established on dialysis, suggesting that a substance crucial for mitochondrial function or substrate supply to mitochondria is removed by dialysis.

Adenosine Diphosphate↗
PubMed1994

Assessment of hepatic iron overload in thalassemic patients by magnetic resonance spectroscopy.

The transverse relaxation time of water protons is shortened by the presence of iron. This shortening depends on the amount and the environment of iron in the sample. We have developed a method for measuring short transverse relaxation time noninvasively by magnetic resonance spectroscopy. To evaluate magnetic resonance spectroscopy as a means of assessing hepatic iron content in patients with transfusional iron overload, we compared the results obtained with this method with those obtained by other means of assessing total body iron content. The correlation between the liver biopsy iron concentration and 1/transverse relaxation time was highly significant (r = 0.95, p < 0.004, n = 6) for iron loads up to 3% dry weight. The correlation between serum ferritin and 1/transverse relaxation time was also significant, but the correlation coefficient was much lower (r = 0.67, p < 0.002, n = 20). The correlation between 24-hr urinary iron excretion and 1/transverse relaxation time was not significant, nor was that between AST and 1/transverse relaxation time. We conclude that magnetic resonance spectroscopic determination of the transverse relaxation time of hepatic water is an accurate method of measuring liver iron content, especially when the iron content is below 3%. Because it is a noninvasive method that is associated with negligible side effects, it could provide clinicians with an excellent means of assessing the effectiveness of the various therapeutic strategies used in the management of patients with iron overload.

Adolescent↗
PubMed1993

An assessment of spin-echo rotating-frame imaging for spatially localized determination of short T2 relaxation times in vivo.

The rotating frame of localized spectroscopy can be augmented by the inclusion of a refocusing pulse to enable the measurement of T2 relaxation times. This technique is particularly appropriate for determining short relaxation parameters due to the absence of time consuming switched B(omicron) field gradients. We have evaluated the accuracy of this protocol by measuring localized T2s in the range of 1 to 20 ms. Preliminary data obtained from muscle and liver of normal and iron overloaded human subjects are also presented.

Magnetic Resonance Imaging↗
PubMed1993

Phosphomonoester is associated with proliferation in human breast cancer: a 31P MRS study.

Phospholipid metabolism of human breast cancer was studied by 31P magnetic resonance spectroscopy (MRS). In vivo localised 31P MR spectra were obtained from the tumour alone using phase modulated rotating frame imaging. For 31 tumours, median (range) phosphomonoester (PME) to ATP ratio was 1.48 (0.57-3.78) and phosphodiester (PDE) to ATP ratio was 1.65 (0.44-3.89). DNA index and S phase fraction (SPF) were measured by flow cytometry of paraffin embedded tissue. Twelve (39%) tumours were diploid and 19 aneuploid. Median (range) SPF for 29 assessable tumours was 5.3% (0.6-28%), with significantly greater median SPF for aneuploid tumours (9.3%) than diploid (3.8%, P = 0.007). There was a significant association between PME/ATP and SPF (P = 0.03) due to a significant correlation for aneuploid tumours (P = 0.01). High resolution 31P MRS of extracts from 18 tumours (including seven studied in vivo) demonstrated that the PME peak consists predominantly of phosphoethanolamine (PE) with a smaller contribution from phosphocholine (PC) (median (range) PE/PC: 3.02 (1.13-5.09)). Changes in PME/ATP were observed for two tumours where tamoxifen stablized disease and may be consistent with the cytostatic effects of this drug.

Adenosine Triphosphate↗
PubMed1992

The use of antisense mRNA to inhibit the tonoplast H+ ATPase in carrot.

Carrot root cells were transformed with the coding or 5' noncoding regions of the carrot vacuolar H+ ATPase A subunit cDNA cloned in the antisense orientation behind the cauliflower mosaic virus 35S promoter. Bafilomycin-sensitive ATPase, H(+)-pumping, and 14C-O-methyl-glucose uptake activities were specifically inhibited in the tonoplast fractions of mutant cell lines. Protein gel blotting confirmed that the expression of the A subunit was inhibited in the tonoplast fraction, but not in the Golgi fraction. Two-dimensional protein gel blots of total microsomes of wild-type and control transformant cell lines revealed two major immunoreactive polypeptides in the acidic pI range. In contrast, highly purified tonoplast membranes contained only the less acidic polypeptide. Because the less acidic polypeptide was preferentially diminished in the two antisense cell lines, we infer that the antisense constructs specifically blocked expression of a tonoplast-specific isoform of the V-ATPase A subunit in carrot. Regenerated plants containing the antisense constructs exhibited altered leaf morphologies and reduced cell expansion. The altered phenotype was correlated with the presence of the antisense construct.

Base Sequence↗
PubMed1991

Quantitative spectroscopy using multiple surface coil probes.

The performance of the rotating frame localization method is discussed, with emphasis on performing the experiment and processing the data in the optimum manner. Studies on phantom samples are presented to illustrate various imperfections which affect the confidence that can be placed on acquired data.

Equipment Design↗
PubMed1990

Multiple quantum filtered 23Na NMR spectroscopy in the perfused heart.

It has been proposed that multiple quantum filtered (MQF) 23Na NMR spectroscopy may distinguish between sodium in the intra- and extracellular spaces, in vivo, and without the requirement for toxic shift reagents. We have investigated the origin of such signals in perfused rat hearts, using shift reagents to discriminate between NMR signals from the two compartments. We find that the observed MQF signal arises predominantly from the extracellular space in the normal heart, and from the intracellular space in the ischaemic heart. However, the quenching effect of the shift reagent may hide some of the extracellular MQF signal, especially during ischaemia. Estimates of intracellular and extracellular relaxation times are obtained and possible mechanisms of the interaction discussed.

Animals↗
PubMed1988

Passive electrical isolation of double coil probes for localized spectroscopy and imaging.

A circuit is described for the electrical isolation of double coil probes where separate transmitter and receiver coils are both tuned to the same frequency and are coupled by mutual inductance. There are only passive components in the probe, and so no additional control signals are required for switching between transmit and receive conditions. An analysis of the operation of the circuit is included together with details of component selection and setting-up procedures, thus facilitating the implementation of the design for a variety of applications in both imaging and spectroscopy.

Computers↗
PubMed1988

Ca2+-ATPase deficiency in a patient with an exertional muscle pain syndrome.

31P Magnetic resonance spectroscopy studies were carried out in vivo on skeletal muscle of a patient with verapamil-responsive, chronic, progressive post-exertional muscle pain. A sister suffered from a similar complaint. The results showed that the muscle: (1) decreased its high energy phosphate content more rapidly than normal during exercise, indicating either increased utilisation or decreased production of ATP; (2) acidified more rapidly than normal during exercise suggesting an increased glycolytic rate; (3) continued in some studies to acidify markedly during the first minute after exercise, indicating that glycolysis remained active into the recovery period; (4) had phosphocreatine and ADP recovery rates consistent with normal rates of oxidative phosphorylation. On the basis of these results, it was proposed that the patient suffers from a defect in Ca2+ handling in the muscle. Subsequently, direct measurement of Ca2+-ATPase activity in the sarcoplasmic reticulum fraction from a muscle biopsy sample showed that the activity of this enzyme was reduced by about 90%.

Adult↗
PubMed1987

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

We have developed 31P NMR spectroscopic methods to determine quantitatively relative levels of phosphorous-containing metabolites in the human myocardium. We have used localization techniques based on the rotating-frame imaging experiment and carried out with a double-surface coil probe. Information is obtained from selected slices by rotating-frame depth selection and from a complete one-dimensional spectroscopic image using phase-modulated rotating-frame imaging. The methods collect biochemical information from metabolites in human heart, and we use the fact that the phosphocreatine/ATP molar ratio in skeletal muscle at rest is higher than that in working heart to demonstrate that localization has been achieved for each investigation. The phosphocreatine/ATP molar ratio in normal human heart has been measured as 1.55 +/- 0.20 (mean +/- SD) (3.5-sec interpulse delay) in six subjects using depth selection and as 1.53 +/- 0.25 (mean +/- SD) in four subjects using spectroscopic imaging. Measurement of this ratio is expected to give a useful and reproducible index of myocardial energetics in normal and pathological states.

Adenosine Triphosphate↗
PubMed1987

The study of human organs by phosphorus-31 topical magnetic resonance spectroscopy.

The potential clinical use of topical magnetic resonance spectroscopy (volume selection by static magnetic field gradients) was tested in 50 studies in volunteers. Topical magnetic resonance spectroscopy (MRS) was shown to be a straightforward method for localising 31P spectra of brain and liver. However, the spherical shape and fixed position of the selected volume posed serious limitations to the study of heart and transplanted kidney by topical MRS. Phosphorus-31 spectra of approximately 30 cm-3 of brain or liver could be obtained in 8 min. Ratios of metabolite concentrations could be determined with a coefficient of variation ranging from 10% to 30%. The ratios of phosphocreatine/ATP and inorganic phosphate/ATP in brain were 1.8 and 0.3, respectively. The ratio of inorganic phosphate/ATP in liver was 0.9. Intracellular pH was 7.03 in brain and 7.24 in liver. The T1 relaxation times of phosphocreatine, inorganic phosphate and gamma-ATP in brain were 4.8 s, 2.5 s and 1.0 s, respectively.

Brain↗