998 resultados para Smith, Charles S.
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On mat: Calvert Bros. & Taylor; Nashville, Tenn.
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Author's autograph on fly-leaf.
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Background: The are currently 2 million people in the UK living with or
after cancer, and this number is expected to double by 2030 (Maddams et
al, 2012). However, many report unmet physical and psychological needs.
Aim: To determine the learning needs of practice nurses to take on an
enhanced role with people affected by cancer, particularly after primary
treatment, and to develop a course to meet these needs.
Method: The Macmillan Steering Group designed and developed a course for practice
nurses to identify their learning needs, enabling participating practice
nurses to work collaboratively with each other and the course facilitator.
There was strong patient involvement throughout. The course was<br/>evaluated by self-assessment of knowledge, skills and confidence, patient
satisfaction questionnaires and in-depth, qualitative telephone interviews<br/>with the participants and their supporting GPs.
Results: The practice nurses reported changed practice, with increased confidence in discussing
issues relating to cancer and its treatment with patients and relatives.
They understood the importance of supported self-management and were
able to signpost patients to appropriate sources of information and
support. Many of the practice nurses started initiating and undertaking
Cancer Care Reviews, both as planned appointments and opportunistically.
Over the past year, a further nine pilots have been completed throughout
the UK, demonstrating that these results are reproducible in other settings.
Conclusions: With appropriate support and training and protected time
to include cancer care into their everyday work, practice nurses can take
on an important role in the support and care of people affected by cancer
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DSDP Leg 73 sediment cores allow direct calibrations of magnetostratigraphy and biostratigraphy for much of the latest Cretaceous to Cenozoic in the mid-latitude South Atlantic Ocean. A complete record of the Cenozoic was not obtained, however, because strong dissolution, poor core recovery and intense core disturbance have masked the biostratigraphy or magnetostratigraphy over some intervals of all recovered sections. DSDP Leg 73 results show the following correlations: Early/middle Miocene in Chron 16 Oligocene/Miocene within Subchron C6CN Eocene/Oligocene within Subchron C13R Middle/late Eocene top of Chron C17 Early/late Paleocene top of Subchron C27N Cretaceous/Tertiary within Subchron C29R
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Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G protein-coupled receptors, which are enzymatically cleaved to expose a truncated extracellular N terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease α-thrombin, is expressed in various tissues (e.g., platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. We have discovered a series of potent peptide-mimetic antagonists of PAR-1, exemplified by RWJ-56110. Spatial relationships between important functional groups of the PAR-1 agonist peptide epitope SFLLRN were employed to design and synthesize candidate ligands with appropriate groups attached to a rigid molecular scaffold. Prototype RWJ-53052 was identified and optimized via solid-phase parallel synthesis of chemical libraries. RWJ-56110 emerged as a potent, selective PAR-1 antagonist, devoid of PAR-1 agonist and thrombin inhibitory activity. It binds to PAR-1, interferes with PAR-1 calcium mobilization and cellular function (platelet aggregation; cell proliferation), and has no effect on PAR-2, PAR-3, or PAR-4. By flow cytometry, RWJ-56110 was confirmed as a direct inhibitor of PAR-1 activation and internalization, without affecting N-terminal cleavage. At high concentrations of α-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, albeit not in human platelets; whereas, at high concentrations of SFLLRN-NH2, RWJ-56110 blocked activation responses in both cell types. Thus, thrombin activates human platelets independently of PAR-1, i.e., through PAR-4, which we confirmed by PCR analysis. Selective PAR-1 antagonists, such as RWJ-56110, should serve as useful tools to study PARs and may have therapeutic potential for treating thrombosis and restenosis.
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Polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants, and some are potent carcinogens in rodents. Carcinogenic PAH are activated in cells to metabolites that react with DNA to form stable covalent DNA adducts. It has been proposed [Cavalieri, E. L. & Roger, E. G. (1995) Xenobiotica 25, 677–688] that unstable DNA adducts are also formed and that apurinic sites in the DNA resulting from unstable PAH adducts play a key role in the initiation of cancer. The potent carcinogen dibenzo[a,l]pyrene (DB[a,l]P) is activated in cells to (+)-syn- and (−)-anti-DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE), which have been shown to form stable adducts with DNA. To evaluate the importance of unstable PAH adducts, we compared stable adduct formation to apurinic site formation. Stable DB[a,l]PDE adducts were determined by 33P-postlabeling and HPLC. To measure apurinic sites they were converted to strand breaks, and these were monitored by examining the integrity of a particular restriction fragment of the dihydrofolate reductase gene. The method easily detected apurinic sites resulting from methylation by treatment of cells or DNA with dimethyl sulfate or from reaction of DNA with DB[a,l]P in the presence of horseradish peroxidase. We estimate the method could detect 0.1 apurinic site in the 14-kb fragment examined. However, apurinic sites were below our limit of detection in DNA treated directly with (+)-syn- or (−)-anti-DB[a,l]PDE or in DNA from Chinese hamster ovary B11 cells so treated, although in these samples the frequency of stable adducts ranged from 3 to 10 per 14 kb. We also treated the human mammary carcinoma cell line MCF-7 with DB[a,l]P and again could not detect significant amounts of unstable adducts. These results indicate that the proportion of stable adducts formed by DB[a,l]P activated in cells and its diol epoxides is greater than 99% and suggest a predominant role for stable DNA adducts in the carcinogenic activity of DB[a,l]P.
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Mode of access: Internet.
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Added t.-p., engraved.
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Vol. 3-7 bear imprint: Printed for subscribers only & not published.
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Mode of access: Internet.
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On spine: History of the African Methodist Episcopal Church, vol. 2.
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Mode of access: Internet.
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Shipping list no.: 91-601-P.