St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

Lipid peroxide formation in microsomes. General considerations

Abstract: 1. Liver microsomes form lipid peroxide when incubated with ascorbate or NADPH, but not with NADH. Increasing the concentration of ascorbate beyond the optimum (0.5mm) decreases the rate of lipid peroxide formation, but this effect does not occur with NADPH. Other reducing agents such as p-phenylenediamine or ferricyanide were not able to replace ascorbate and induce lipid peroxide formation. 2. The rate of ascorbate-induced peroxidation is optimum at pH6.0 whereas the rate of the NADPH system is optimum at pH7.0. Both systems require phosphate for maximum activity. 3. Lipid peroxide formation occurs at the maximum specific rate in very dilute microsome suspensions (0.15mg. of protein/ml.). 4. Treatment of microsomes with deoxycholate and other detergents causes membrane disintegration and inhibits lipid peroxide formation. 5. Lipid peroxide formation is accompanied by a rapid uptake of oxygen and there is a large excess of oxygen utilized for each molecule of malonaldehyde measured in the peroxide method. 6. Boiled microsomes form lipid peroxide in the presence of ascorbate, but not if NADPH is added. 7. Lipid peroxide formation induced by NADPH is strongly inhibited by p-chloromercuribenzoate, weakly inhibited by N-ethylmaleimide and unaffected by iodoacetamide. Ascorbate-induced peroxidation in untreated microsomes is unaffected by p-chloromercuribenzoate, but inhibited if boiled microsomes are used. These experiments may be interpreted on the basis that a ferredoxin-type protein forms part of the system in which NADPH induces lipid peroxide formation. 8. Most heavy-metal ions, with the exception of inorganic iron (Fe(2+) or Fe(3+)), which activates, inhibit both ascorbate-induced and NADPH-induced peroxidation. Mg(2+) increases the rate of peroxidation whereas Ca(2+) inhibits it. 9. Lipid peroxide formation is inhibited strongly by GSH and weakly by cysteine. Ascorbate-induced peroxidation is much more sensitive than NADPH-induced peroxidation. 10. Peroxidation is strongly inhibited by addition of low concentrations (0.01-0.1mm) of cytochrome c or of haemoglobin. 11. It is considered that lipid peroxide formation occurs as a result of the operation of the microsomal electron-transport chain switching from hydroxylation to oxidize unsaturated lipids of the endoplasmic reticulum.

Calcitonin alters behaviour of isolated osteoclasts.

Abstract: Osteoclasts were incubated on a glass or plastic substrate and the effect of calcitonin (CT) on their behaviour was observed. Before exposure to CT the osteoclasts were actively motile, the cytoplasm advancing behind broad pseudopodial (lamellipodial) processes which showed intense ruflling activity. CT caused cessation of lamellipodial activity within minutes, followed by gradual fragmentation and retraction of lamellipodia. Complete osteoclast quiescence was regularly induced by concentrations of CT above 50 pg/ml, and lesser degrees of quiescence were induced at concentrations down to 10 pg/ml. This quiescent state was reversed on removing CT from the medium, and was abrogated by prior treatement of osteoclasts with trypsin. The quiescent state did not reduce the longevity of the cells in culture. nor did it affect their resistance to removal from glass by trypsin. CT showed no influence on the pseudopodial activity of osteoblasts, peritoneal macrophages or inflammatory giant cells. Osteoclast quiescence seems to be a reversible state induced by the interaction of CT with a trypsin-sensitive CT receptor, present on osteoclasts. The range of concentrations which induce partial osteoclast quiescence are within the physiological range of serum concentrations in man, and this suggests that CT plays a physiological role in the regulation of osteoclast activity. The behavioural change induced by CT in osteoclasts may help to identify the precursor cell of the osteoclast and may assist investigations into the mechanism of control of osteoclasis.

By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction.

Abstract: OBJECTIVE--To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN--Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE--Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS--In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS--The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.

The assessment of vertebral deformity: a method for use in population studies and clinical trials

Abstract: The absence of specific criteria for the definition of vertebral fracture has major implications for assessing the apparent prevalence and incidence of vertebral deformity. Also, little is known of the effect of using different criteria for new vertebral fractures in clinical studies. We therefore developed radiological criteria for vertebral fracture in women for assessing both the prevalence and the incidence of vertebral osteoporosis in population and in prospective studies and compared these with several other published methods. Normal ranges for vertebral shape were obtained from radiographs in 100 women aged 45-50 years. These included ranges for the ratios of anterior/posterior, central/posterior and posterior/predicted posterior vertebral heights from T4 to L5. The predicted posterior height was calculated from adjacent vertebrae. In contrast to other methods, our definition of fracture required the fulfillment of two criteria at each vertebral site, and was associated with a lower apparent prevalence of fracture in the control women due to a lower false positive rate. The prevalence and incidence of vertebral deformity using different criteria were then compared in a series of women with skeletal metastases from breast cancer in whom radiographs were obtained 6 months apart. The prevalence of vertebral deformity and the specificity for deformity varied markedly with differing criteria. Using a cut-off of 3 standard deviations the prevalence of vertebral deformity in the women with breast cancer was 46%. Using other methods, the prevalences of deformity ranged from 33% to 74%. Over a 6-month interval 25% of patients with breast cancer sustained 61 deformities using our method, of which only 8% resulted from errors in reproducibility. The number of patients sustaining new deformities was increased twofold when assessed by other methods (45%-53%), but errors of reproducibility may have accounted for 21% of the new deformities. The magnitude and distribution of these errors have important implications for the apparent therapeutic efficacy of agents in clinical trials of osteoporosis. The rapid semi-automated technique for assessing vertebral deformities on lateral spine radiographs that we have developed has a high specificity, and reduces the impact of errors of reproducibility on estimates of prevalence and incidence. The method should prove a value in assessing vertebral deformity both in population studies and in prospective clinical trials.

A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias.

Abstract: Some acute lymphocytic leukaemias, particularly those in young children, are associated with a t(4;11)(q21;q23) reciprocal translocation. We have cloned the translocation breakpoint on chromosome 11q23 and isolated corresponding RNA transcripts from this region. The translocation occurs within a cluster of Alu repetitive elements located within an intron of a gene that gives rise to 11.5 (kb) transcript spanning the translocation breakpoint. The 11.5 kb transcript encodes a protein that is highly homologous to the Drosophila trithorax gene, a developmental regulator. An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region.