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Biomedical subjects

D J Taylor

Publications and source records attributed to D J Taylor.

At least 109 records · Page 6Linked to original sources

A New High-Flux Chemical and Materials Crystallography Station at the SRS Daresbury. 1. Design, Construction and Test Results.

A new single-crystal diffraction facility has been constructed on beamline 9 of the SRS at Daresbury Laboratory for the study of structural problems in chemistry and materials science. The station utilizes up to 3.8 mrad horizontally from the 5 T wiggler magnet which can be focused horizontally and vertically. The horizontal focusing is provided by a choice of gallium-cooled triangular bent Si (111) or Si (220) monochromators, giving a wavelength range from 0.3 to 1.5 A. Focusing in the vertical plane is achieved by a cylindrically bent zerodur mirror with a 300 mum-thick palladium coating. The station is equipped with a modified Enraf-Nonius CAD-4 four-circle diffractometer and a Siemens SMART CCD area-detector system. High- and low-temperature facilities are available to cover the temperature range from about 80 to 1000 K. Early results on test compounds without optimization of the beam optics demonstrate that excellent refined structures can be obtained from samples giving diffraction patterns too weak to be measured with conventional laboratory X-ray sources, fulfilling a major objective of the project.

Journal Article↗

Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase: regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels.

The role of p38 mitogen-activated protein kinase (MAPK) in responses of human fibroblasts and vascular endothelial cells to IL-1 was investigated by use of a pyridinyl imidazole compound (SB 203580), which specifically inhibits the enzyme. SB 203580 inhibited (50% inhibitory concentration approximately 0.5 microM) IL-1-induced phosphorylation of heat shock protein 27 (an indicator of p38 MAPK activity) in fibroblasts without affecting the other known IL-1-activated protein kinase pathways (p42/p44 MAPK, p54 MAPK/c-Jun N-terminal kinase and beta-casein kinase). SB 203580 significantly inhibited IL-1-stimulated IL-6, (30 to 50% at 1 microM) but not IL-8 production from human fibroblasts (gingival and dermal) and umbilical vein endothelial cells. IL-1 induction of steady state level of IL-6 mRNA was not significantly inhibited, which is consistent with p38 MAPK regulating IL-6 production at the translational level. SB 203580 strongly inhibited IL-1-stimulated PG production by fibroblasts and human umbilical vein endothelial cells. This was associated with the inhibition of the induction of PGH synthase-2 protein and mRNA. SB 203580 also inhibited the stimulation of collagenase-1 and stromelysin-1 production by IL-1 without affecting synthesis of the tissue inhibitor of metalloproteinases (TIMP)-1. SB 203580 prevented the increase in collagenase-1 and stromelysin-1 mRNA stimulated by IL-1. In a model of cartilage breakdown, short-term IL-1-stimulated proteoglycan resorption and inhibition of proteoglycan synthesis were unaffected by SB 203580, while longer term collagen breakdown was prevented. It is concluded that 1) p38 MAPK plays an important role in the regulation of some, but not all, responses to IL-1, and 2) it is involved in the regulation of mRNA levels of some IL-1-responsive genes.

Calcium-Calmodulin-Dependent Protein Kinases↗

Ban on avoparcin.

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Animal Diseases↗

In vivo skeletal muscle mitochondrial function in Leber's hereditary optic neuropathy assessed by 31P magnetic resonance spectroscopy.

We used 31P magnetic resonance spectroscopy (31P-MRS) to assess in vivo skeletal muscle mitochondrial function in 10 Leber's hereditary optic neuropathy patients/carriers with a mitochondrial DNA (mtDNA) mutation at one of three nucleotide positions, 11,778, 14,484, and 3,460. We studied one affected patient for each mutation and two unaffected carriers with the 11,778 or 3,460 mutation and three carriers with 14,484. All subjects were homoplasmic except the two 3,460 carriers, who showed 80% and 15% of mutated mtDNA. 31P-MRS at rest disclosed some abnormalities in all subjects. In particular, the phosphorylation potential was below the normal range in all cases. During recovery from exercise, the maximum rate of mitochondrial ATP production (Vmax) was reduced to 27% of normal in the 11,778 mutation and to 53% in the 14,484 mutation patient/carrier groups. Mitochondrial Vmax was within the normal range in all subjects with the 3,460 mutation but correlated inversely with the percentage of mutated mtDNA. This in vivo study shows that the 11,778 mutation causes a mitochondrial impairment more severe than the 14,484 and that the 3,460 mutation results in only a mild depression of muscle mitochondrial function.

Adult↗

Proton efflux in human skeletal muscle during recovery from exercise.

In recovery from exercise, phosphocreatine resynthesis results in the net generation of protons, while the net efflux of protons restores pH to resting values. Because proton efflux rate declines as pH increases, it appears to have an approximately linear pH-dependence. We set out to examine this in detail using recovery data from human calf muscle. Proton efflux rates were calculated from changes in pH and phosphocreatine concentration, measured by 31P magnetic resonance spectroscopy, after incremental dynamic exercise to exhaustion. Results were collected post hoc into five groups on the basis of end-exercise pH. Proton efflux rates declined approximately exponentially with time. These were rather similar in all groups, even when pH changes were small, so that the apparent rate constant (the ratio of efflux rate to pH change) varied widely. However, all groups showed a consistent pattern of decrease with time; the halftimes of both proton efflux rate and the apparent rate constant were longer at lower pH. At each time-point, proton efflux rates showed a significant pH-dependence [slope 17 (3) mmol x l(-1) x min(-1) x pH unit(-1) at the start of recovery, mean (SEM)], but also a significant intercept at resting pH [16 (3) mmol x l(-1) x min(-1) at the start of recovery]. The intercept and the slope both decreased with time, with halftimes of 0.37 (0.06) and 1.4 (0.4) min, respectively. We conclude that over a wide range of end-exercise pH, net proton efflux during recovery comprises pH-dependent and pH-independent components, both of which decline with time. Comparison with other data in the literature suggests that lactate/proton cotransport can be only a small component of this initial recovery proton efflux.

Adult↗

Hospitalizations for severe complications of pregnancy, 1987-1992.

OBJECTIVE: To compute ratios of severe pregnancy complications (the number of hospitalizations for pregnancy complications per 100 deliveries) and to examine factors associated with their prevalence. METHODS: Using population-based California hospital discharge data to estimate hospitalization ratios of pregnancy complications during 1987-1992, we defined cases by preselected pregnancy complication codes from the International Classification of Diseases, Ninth Revision, Clinical Modification, excluding induced abortions and delivery-associated complications. All hospital deliveries of liveborn or stillborn infants were included in our denominator. We examined ratios by age, race-ethnicity, payment source, total hospitalization charges, and length of hospital stay. RESULTS: There were 833,264 hospitalizations for pregnancy complications in California (25 complications per 100 deliveries), which included admissions for preterm labor (33%), genitourinary infection (16%), and pregnancy-induced hypertension (15%). Age-specific ratios were highest for women 14 years old and younger (38 per 100 deliveries) and lowest for women 25-29 years old (23 per 100 deliveries). Ratios of complications varied by race-ethnicity; black women had the highest (42 per 100 deliveries), and Asian-Pacific Islander women had the lowest (21 per 100 deliveries). Ratios were unaffected by payment source. In 1987, Medicaid charges were $118 million for 33% of the number of total hospitalizations for complications. In 1992, such Medicaid hospitalizations accounted for $356 million (49%) of the $734 million in total charges and for 183,295 (45%) of the 409,000 total hospital days. CONCLUSION: Our results showed disparities in ratios of severe complications of pregnancy by age and race-ethnicity as well as a shift of financial burden to Medicaid. These findings suggest that such complications may be reduced by identifying risk factors and targeting high-risk groups.

Adolescent↗

Correlative MR imaging and 31P-MR spectroscopy study in sarcoglycan deficient limb girdle muscular dystrophy.

We combined magnetic resonance (MR) imaging and phosphorus magnetic resonance spectroscopy (31P-MRS) to study skeletal muscle in seven patients with limb girdle muscular dystrophy (LGMD) with a variable deficiency of the alpha-, beta-, and gamma-sarcoglycan but normal dystrophin expression on muscle biopsy. T1- and T2-weighted spin-echo axial leg images showed the highest degree of fat replacement in soleus, tibialis anterior and peroneal muscles while gastrocnemius and tibialis posterior were less affected. In LGMD patients as a group, calf muscle phosphorylated compound content did not differ from controls, but the cytosolic pH was increased (P = 0.02). The degree of calf muscle fat replacement correlated inversely with cytosolic pH (r = 0.74) and directly with PCr/ATP (r = 0.74). Muscle oxidative metabolism was normal in LGMD patients. Our findings show that primary deficits of sarcoglycan complex lead to specific morphological and metabolic patterns of skeletal muscle involvement.

Adolescent↗

A cross-sectional study of changes in fetal renal size with gestation in appropriate- and small-for-gestational-age fetuses.

This cross-sectional study aimed to determine whether there are differences in kidney size and shape in small- and appropriate-for-gestational-age fetuses at different gestations. In the Fetal Growth Clinic of a large university hospital in England, 219 singleton fetuses were studied cross-sectionally at different gestational ages from 22 to 38 weeks. At each gestational age, the fetal kidney length, circumference and anterior-posterior and transverse diameters were measured using an Aloka 650 SL machine. At birth, the fetuses were classified as small or appropriate for gestational age, depending on the birth weight centile; the various kidney measurements for the two groups were compared. The kidney lengths at different gestational ages were similar in the two groups. The circumference and transverse and anterior-posterior diameters were significantly greater in the appropriate-for-gestational-age fetuses from about 28 weeks' gestation. We conclude that differences in fetal kidney size with gestation manifest from as early as 26-28 weeks. The differentially smaller anterior-posterior and transverse kidney diameters in small-for-gestational age fetuses, resulted in altered renal morphology, producing sausage-shaped kidneys.

Adult↗

Skeletal muscle metabolism in myotonic dystrophy A 31P magnetic resonance spectroscopy study.

We have used 31P magnetic resonance spectroscopy to investigate skeletal muscle bioenergetics in a total of 31 patients with myotonic dystrophy. Results from resting flexor digitorum superficialis and calf muscle showed a significant elevation in the concentration ratio of inorganic phosphate to ATP and a significant reduction in the phosphorylation potential. In addition, in resting calf muscle the concentration ratio of phosphocreatine to ATP was reduced, and the resting intracellular pH and calculated free cytosolic ADP concentration were elevated. In general, the abnormalities observed were more marked in those patients who were more severely affected as judged by their ability to exercise. During aerobic exercise in both calf muscle and flexor digitorum superficialis, phosphocreatine was depleted more rapidly in patients than in control subjects but the muscle acidified less and ADP concentrations were higher. Calculated ATP turnover was significantly elevated. Analysis of the recovery kinetics for phosphocreatine following exercise provides evidence for a small but significant reduction in mitochondrial function. Analysis of the response of flexor digitorum superficialis to ischaemic exercise provides evidence of a reduction in the relative utilization of glycogen to produce ATP which may account, in part, for the reduced acidification seen in exercising muscle in myotonic dystrophy. There was no definite evidence of an alteration in proton handling capacity in this condition.

Adenosine Diphosphate↗

Accuracy of oscillometric blood pressure monitoring in pregnancy and pre-eclampsia.

OBJECTIVE: To assess the accuracy of the Omron HEM 705 CP oscillometric device for the measurement of blood pressure in pregnancy and pre-eclampsia. SETTING: Two teaching hospitals. PARTICIPANTS: Eighty-five pregnant women with a wide range of blood pressures, and 43 women with pre-eclampsia. METHODS: Evaluation was carried out according to the British Hypertension Society protocol, incorporating criteria of the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: Mean differences (device minus observer) for systolic blood pressure were -0.9 mmHg (SD 10) in normal pregnancy, and -2 mmHg (SD 10) in the women with pre-eclampsia. For diastolic blood pressure, Korotkoff phase V, the differences were -1.5 mmHg (SD 10), and -8 mmHg (SD 8) respectively; i.e. the device consistently under-read the diastolic blood pressure in pre-eclamptic women by a mean of 8 mmHg when compared with conventional sphygmomanometry. Korotkoff phase IV could not be accurately reproduced. According to the British Hypertension Society grading criteria, the device reached a 'B' grading in the 85 pregnant women. In pre-eclampsia only a 'C' grade was reached for systolic blood pressure, and 'D' grade for diastolic blood pressure. Accuracy criteria stipulated by the AAMI were not met in any situation. CONCLUSION: The Omron HEM 705 CP does not reach acceptable accuracy criteria for blood pressure measurement when compared with trained observers in women with pre-eclampsia, as judged by the British Hypertension Society Protocol. It also failed to meet the AAMI criteria, although the methodology stipulated by the AAMI may not be applicable to a pregnancy population.

Blood Pressure↗

Automated blood pressure measurement as a predictor of proteinuric pre-eclampsia.

OBJECTIVES: To investigate the relation between antenatal clinic, obstetric day unit and 24-hour ambulatory blood pressure measurements and 24-hour proteinuria levels in hypertensive pregnancies. DESIGN: An observational study. PARTICIPANTS: Forty-eight women presenting with new hypertension after 20 weeks of gestation. RESULTS: The closest relation was found between ambulatory blood pressure measurements and 24-hour proteinuria levels. No significant relation was found between the conventional diastolic blood pressure threshold of 90 mmHg and 24-hour proteinuria levels. CONCLUSIONS: Ambulatory blood pressure measurement gives better information about disease status in pre-eclampsia as assessed by proteinuria than does conventional sphygmomanometry.

Adolescent↗

Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy.

OBJECTIVE: To determine the skeletal muscle metabolic manifestations of familial hypertrophic cardiomyopathy. DESIGN: A case-control study. SETTING: 31P magnetic resonance spectroscopy of the calf muscle was performed on volunteers from a centre specialising in familial hypertrophic cardiomyopathy. PATIENTS: Five patients with abnormal beta myosin heavy chain protein in cardiac and skeletal muscle and five patients with a troponin T abnormality in cardiac muscle were compared with healthy controls. RESULTS: High energy phosphate metabolism in vivo was examined in a non-invasive manner. In resting muscle, the beta myosin heavy chain group had a higher ratio of phosphocreatine to ATP concentration (4.51 (SD 0.17)) than either the troponin T group (3.88 (0.42)) or controls (n = 16; 4.04 (0.40)). Exercise duration was reduced compared to controls, and during the fourth minute of exercise phosphocreatine depletion and muscle acidification were greater in both patient groups. After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes). CONCLUSIONS: Exercise metabolism was abnormal in both groups of subjects, and the affected contractile protein determined the metabolic changes in muscle at rest and during recovery. In patients with abnormal beta myosin heavy chain protein, there was a decrease in oxidative capacity consistent with the reduction in mitochondria reported in muscle biopsy studies of similar patients.

Adenosine Triphosphate↗

Intracellular free magnesium concentrations in skeletal muscle in chronic uraemia.

Low intracellular free magnesium concentrations ([Mg2+]i) are associated with essential hypertension and may reflect a disordered cellular ionic environment. 31P magnetic resonance spectroscopy was used to study skeletal muscle [Mg2+]i in a group of chronic renal failure (CRF) patients and data were compared with a group of control subjects of similar age. Other data including the patients' blood pressure, medication and plasma biochemistry were collected. There was a significant inverse correlation of [Mg2+]i with systolic (p < 0.001) and diastolic blood pressure (p < 0.05) in the CRF population. In CRF [Mg2+]i was similar (0.52 +/- 0.01 mM, SEM) to controls (0.53 +/- 0.01 mM; p = 0.20), even if just the normotensive patients and controls were compared. There was no correlation of [Mg2+]i with plasma parathyroid hormone, total [Mg2+] or [Ca2+]. Similar to studies in subjects with essential hypertension, these data support a role for [Mg2+]i specifically, and an abnormal intracellular environment more generally, in the pathophysiology of hypertension in CRF.

Adult↗

Laparoscopic laser treatment for endometriosis.

The advent of the use of laparoscopy and lasers in gynaecology has added a further option for the treatment of endometriosis. This study is a retrospective review of the notes of 28 women who had endometriosis treated laparoscopically with an Nd:YAG laser. Results were assessed by subjective reporting of symptoms. Seventy-three percent of patients reported significant or complete resolution of symptoms at three to 26 months follow-up. No major complications were encountered. The results suggest this offers a further treatment option for endometriosis which merits further evaluation.

Adult↗