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991.
Jane Derges Rebecca Lynch Angela Clow Mark Petticrew Alizon Draper 《Critical public health》2012,22(4):419-425
During a ‘Well London’ study, residents were asked about their neighbourhood and its environment. Above all other complaints, ‘dog poo’ was mentioned as a key concern. Despite low rates of infection and disease among the human population resulting from contact with canine faecal matter, the concerns of the public continue to rate it as a serious public health issue. Most public health studies, therefore, seek to identify processes of transmission and disease pathology as a method of addressing the problem. This study approaches the issue through a contextualised analysis of residents’ complaints, using anthropological theory to examine the symbolic representation of ‘dog poo’. Analysis of the interviews shows that these specific complaints were located among less easily defined or articulated experiences of social and environmental neglect, where neighbours were estranged from one another and local authorities seen as negligent. This approach has important implications for public health, as it provides not only a strong indicator of the level of dissatisfaction within some of London's more disadvantaged neighbourhoods, but also identifies a need for policies that are grounded in cross-disciplinary research into the relationship between health, ‘wellbeing’ and experiences of marginalisation among urban populations. 相似文献
992.
993.
In vitro evaluation of prothrombin complex concentrates in a thrombin generation assay, using DAPA and purified components of the prothrombinase complex, demonstrated significant levels of coagulant- active "phospholipid replacing" activity. Quantification of this activity showed a significant correlation (r = 0.8747, p less than 0.01) with thrombogenicity measured in vivo in a stasis model in rabbits. Extracted lipid material retained full phospholipid replacing activity in the vitro assay. Thin-layer chromatographic characterization confirmed the presence of phospholipids with known coagulant activity in vitro. In vivo, the extracted material was nonthrombogenic but augmented the thrombogenicity of purified factor Xa. Substitution of a synthetic coagulant-active phospholipid (phosphatidylcholine-phosphatidylserine lipid vesicles) for the extracted phospholipid produced a similar augmentation of a factor-Xa- induced thrombogenicity in vivo. It is concluded that the coagulant- active phospholipid content of prothrombin complex concentrates is a major determinant of thrombogenicity but requires the presence of activated clotting factors for its expression in vivo. 相似文献
994.
Atrial natriuretic factor receptors in rat kidney, adrenal gland, and brain: Autoradiographic localization and fluid balance dependent changes 总被引:1,自引:1,他引:1
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David R. Lynch Karen M. Braas Soloman H. Snyder 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(10):3557-3561
Mammalian atria contain natriuretic peptides designated atrial natriuretic factors (ANF). Using in vitro autoradiography with 125I-labeled ANF, we have localized high-affinity (Kd = 150 pM) ANF binding sites to the glomeruli of the kidney, zona glomerulosa of the adrenal gland, and choroid plexus of the brain. The numbers of sites in both kidney and adrenal are increased in rats deprived of water; increases are detectable within 72 hr of water deprivation in the kidney and within 24 hr in the adrenal gland. Receptor numbers decline in rats given 2.0% NaCl as drinking water and in diabetic rats. The discrete localizations and dynamic alterations of these receptors suggest that ANF regulates fluid balance through diverse but coordinated effects on receptors in numerous organs including the kidney, adrenal, and brain. 相似文献
995.
Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old 总被引:20,自引:0,他引:20
Meaume S Rudnichi A Lynch A Bussy C Sebban C Benetos A Safar ME 《Journal of hypertension》2001,19(5):871-877
BACKGROUND: Aortic pulse wave velocity (PWV) is a significant and independent predictor of cardiovascular diseases (CVD) in hypertensive subjects and in patients with end-stage renal disease, but its contribution to cardiovascular risk in subjects between 70 and 100 years old has never been tested. PATIENTS: A cohort of 124 subjects (mean age: 87 +/- 7 years) was studied in two geriatric departments in a Paris suburb. Together with sphygmomanometric blood pressure measurements, aortic PWV was measured using a validated automatic device. RESULTS: Blood pressure, heart rate and body mass index, but not age, explained 48% of the PWV variability in this cohort. Furthermore, PWV was the major factor predicting the presence of CVD. The adjusted odds ratio was 17.44 (95% confidence intervals: 2.52-120.55). Antihypertensive drug therapy and low plasma albumin level had only an additive role. Blood pressure, particularly pulse pressure, had no predictive value. CONCLUSION: In 70-100-year-old subjects, aortic PWV is a strong independent marker of CVD, a finding that remains to be to confirmed by long-term longitudinal studies. 相似文献
996.
997.
A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease 总被引:1,自引:0,他引:1
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Lynch PJ Tong J Lehane M Mallet A Giblin L Heffron JJ Vaughan P Zafra G MacLennan DH McCarthy TV 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(7):4164-4169
Central core disease is a rare, nonprogressive myopathy that is characterized by hypotonia and proximal muscle weakness. In a large Mexican kindred with an unusually severe and highly penetrant form of the disorder, DNA sequencing identified an I4898T mutation in the C-terminal transmembrane/luminal region of the RyR1 protein that constitutes the skeletal muscle ryanodine receptor. All previously reported RYR1 mutations are located either in the cytoplasmic N terminus or in a central cytoplasmic region of the 5,038-aa protein. The I4898T mutation was introduced into a rabbit RYR1 cDNA and expressed in HEK-293 cells. The response of the mutant RyR1 Ca2+ channel to the agonists halothane and caffeine in a Ca2+ photometry assay was completely abolished. Coexpression of normal and mutant RYR1 cDNAs in a 1:1 ratio, however, produced RyR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca2+ release were reduced by 67%. [3H]Ryanodine binding indicated that the heterozygous channel is activated by Ca2+ concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca2+ level and a significantly reduced luminal Ca2+ level. These data are indicative of a leaky channel, possibly caused by a reduction in the Ca2+ concentration required for channel activation. Comparison with two other coexpressed mutant/normal channels suggests that the I4898T mutation produces one of the most abnormal RyR1 channels yet investigated, and this level of abnormality is reflected in the severe and penetrant phenotype of affected central core disease individuals. 相似文献
998.
Effects of recombinant human granulocyte-macrophage colony-stimulating factor on intracellular pH in mature granulocytes 总被引:1,自引:0,他引:1
Sullivan R; Griffin JD; Wright J; Melnick DA; Leavitt JL; Fredette JP; Horne JH Jr; Lyman CA; Lazzari KG; Simons ER 《Blood》1988,72(5):1665-1673
We studied the effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSFrh) on the internal pH of granulocytes using the fluorescent probe BCECF. GM-CSFrh did not directly alter the resting pH of granulocytes isolated from the peripheral blood; however, when the cells were preincubated for 90 minutes with the growth factor and then activated with the chemotactic peptide N-formyl met leu phe (fMLP), they exhibited both an acceleration in the initial rate of acidification and a marked delay in realkalinization. The kinetic changes both in initial acidification and in subsequent realkalinization induced by GM-CSFrh priming were not prevented by protein synthesis inhibitors and were observed in granulocytes harvested from patients with both sex-linked and autosomal recessive chronic granulomatous disease (CGD). By directly quantitating H+ ion secretion, by monitoring the effects of sodium repletion on intracellular pH, and through use of the sodium channel inhibitors amiloride and dimethyl amiloride and the Na+/K+-ATPase inhibitor ouabain, we showed that the altered kinetics of intracellular acidification and alkalinization following fMLP stimulation of GM-CSFrh- primed granulocytes could not be accounted for by changes in transmembrane proton exportation regulated by the Na+/H+ antiport channel. Although the initial acidification following fMLP was abrogated by 2-deoxy-D-glucose in both GM-CSFrh-pretreated and GM-CSFrh- untreated granulocytes, retardation of the subsequent phase of alkalinization was observed in GM-CSFrh-primed cells even after inhibition of both glycolytic and mitochondrial metabolism. Our data indicate that the increased cytosolic acidification following fMLP stimulation in granulocytes "primed" with GM-CSFrh does not result from disordered proton excretion but instead from increased release of intracellular free acid which is only partially coupled to glucose catabolism or to the generation of superoxide anion (O2-). 相似文献
999.
The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam 总被引:24,自引:0,他引:24
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Lynch BA Lambeng N Nocka K Kensel-Hammes P Bajjalieh SM Matagne A Fuks B 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(26):9861-9866
Here, we show that the synaptic vesicle protein SV2A is the brain binding site of levetiracetam (LEV), a new antiepileptic drug with a unique activity profile in animal models of seizure and epilepsy. The LEV-binding site is enriched in synaptic vesicles, and photoaffinity labeling of purified synaptic vesicles confirms that it has an apparent molecular mass of approximately 90 kDa. Brain membranes and purified synaptic vesicles from mice lacking SV2A do not bind a tritiated LEV derivative, indicating that SV2A is necessary for LEV binding. LEV and related compounds bind to SV2A expressed in fibroblasts, indicating that SV2A is sufficient for LEV binding. No binding was observed to the related isoforms SV2B and SV2C. Furthermore, there is a high degree of correlation between binding affinities of a series of LEV derivatives to SV2A in fibroblasts and to the LEV-binding site in brain. Finally, there is a strong correlation between the affinity of a compound for SV2A and its ability to protect against seizures in an audiogenic mouse animal model of epilepsy. These experimental results suggest that SV2A is the binding site of LEV in the brain and that LEV acts by modulating the function of SV2A, supporting previous indications that LEV possesses a mechanism of action distinct from that of other antiepileptic drugs. Further, these results indicate that proteins involved in vesicle exocytosis, and SV2 in particular, are promising targets for the development of new CNS drug therapies. 相似文献
1000.