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- Armstrong, Lucas C., et al.
(författare)
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Thrombospondin 2 Inhibits Microvascular Endothelial Cell Proliferation by a Caspase-independent Mechanism
- 2002
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Ingår i: Molecular Biology of the Cell. - : American Society for Cell Biology. - 1059-1524 .- 1939-4586. ; 13:6, s. 1893-1905
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Tidskriftsartikel (refereegranskat)abstract
- The matricellular protein thrombospondin 2 (TSP2) regulates a variety of cell–matrix interactions. A prominent feature of TSP2-null mice is increased microvascular density, particularly in connective tissues synthesized after injury. We investigated the cellular basis for the regulation of angiogenesis by TSP2 in cultures of murine and human fibroblasts and endothelial cells. Fibroblasts isolated from murine and human dermis synthesize TSP2 mRNA and secrete significant amounts of immunoreactive TSP2, whereas endothelial cells from mouse lung and human dermis did not synthesize TSP2 mRNA or protein. Recombinant mouse TSP2 inhibited growth of human microvascular endothelial cells (HMVECs) mediated by basic fibroblast growth factor, insulin-like growth factor-1, epidermal growth factor, and vascular endothelial growth factor (VEGF). HMVECs exposed to TSP2 in the presence of these growth factors had a decreased proportion of cells in S and G2/M phases. HMVECs cultured with a combination of basic fibroblast growth factor, insulin-like growth factor-1, and epidermal growth factor displayed an increased proportion of nonviable cells in the presence of TSP2, but the addition of VEGF blocked this TSP2-mediated impairment of cell viability. TSP2-mediated inhibition of DNA synthesis by HMVECs in the presence of VEGF was not affected by the broad-spectrum caspase inhibitor zVAD-fmk. Similar findings were obtained with TSP1. Taken together, these observations indicate that either TSP2 or TSP1 can inhibit HMVEC proliferation by inhibition of cell cycle progression and induction of cell death, but the mechanisms responsible for TSP2-mediated inhibition of cell cycle progression are independent from those leading to cell death.
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| 5. |
- James, Stefan K., et al.
(författare)
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A rapid troponin I assay is not optimal for determination of troponin status and prediction of subsequent cardiac events at suspicion of unstable coronary syndromes.
- 2004
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Ingår i: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 93:2-3, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Troponin is a specific marker of myocardial damage. For early prediction of coronary events in patients with suspicion of acute coronary syndromes the assay also needs to be highly sensitive. METHODS AND RESULTS: A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial. A quantitative troponin T analysis was later performed on blood samples obtained at randomization by a central laboratory. There was an agreement between the rapid troponin I assay and troponin T (< or =/>0.1 microg/l) in 3596 (80.9%) patients. A positive rapid troponin I was identifying any elevation of troponin T (>0.01 microg/l) in 1990 patients (90.4%) whereas a negative rapid troponin I was corresponding to negative troponin T (< or =0.01 microg/l) in only 1217 patients (54.2%). Patients with a positive versus negative rapid troponin I had an increased risk of death or myocardial infarction at 30 days (9.3 vs. 5.9%; odds ratio, O.R. 1.64; 95% confidence interval, 1.31-2.06). Troponin T elevation (>0.1 microg/l) provided a better (10.5 v. 4.9%, O.R. 2.26; C.I. 1.79-2.85) risk stratification. Regardless of a positive or a negative rapid troponin I, the troponin T result (>0.1 vs. < or =0.1 microg/l) stratified the patients into high and low risk of events at 30 days, (10.3 vs. 5.7%, P=0.002) and (11.5 vs. 4.8%, P<0.001), respectively. CONCLUSION: In a population with non-ST elevation acute coronary syndrome a positive rapid troponin I assay is a specific indicator of troponin elevation and a predictor of early outcome. However, a negative rapid troponin I is not a reliable indicator of the absence of myocardial damage and does not indicate a low risk of subsequent cardiac events. A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial and related to a centrally analyzed quantitative troponin T test. A positive rapid troponin I was well corresponding to any elevation of troponin T (>0.01 microg/l) and predicted an unfavorable outcome at 30 days. However, a negative rapid troponin I was corresponding to troponin T < or =0.01 microg/l in only half of the patients. Troponin T >0.1 microg/l vs. < or =0.1 microg/l provided a better risk stratification than the rapid troponin I result. For patients with troponin T elevation (>0.1 microg/l) the 30 day event rate was high regardless of the rapid troponin I result.
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| 7. |
- James, Stefan, et al.
(författare)
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Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome : prospective verification in the GUSTO-IV trial
- 2003
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Ingår i: American Journal of Medicine. - 0002-9343 .- 1555-7162. ; 115:3, s. 178-184
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A third-generation troponin T assay with improved precision and a lower detection limit has been developed. However, the appropriate cutoff for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality has not been established. METHODS: A retrospective evaluation of data from the Fragmin and fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial suggested that a cutoff below 0.1 microg/L for troponin T levels might be more useful in risk stratification. A prospective validation of two cutoff levels (0.03 microg/L and 0.01 microg/L) was performed in 7115 patients with non-ST-elevation acute coronary syndrome from the Global Utilization of Strategies To open Occluded arteries IV (GUSTO-IV) trial. RESULTS: Patients with troponin T levels >0.1 microg/L had greater 30-day mortality (5.5% [201/3679]) than did those with levels CONCLUSION: Using a cutoff of
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| 9. |
- Scherstén, Anders, et al.
(författare)
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Dating mafic–ultramafic intrusions by ion-microprobing contact-melt zircon: examples from SW Sweden
- 2000
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Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 39:1, s. 115-125
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Tidskriftsartikel (refereegranskat)abstract
- Zircons from anatectic melts of the country rocks of three Proterozoic mafic–ultramafic intrusions from the Sveconorwegian Province in SW Sweden were microanalyzed for U–Th–Pb and rare earth elements. Melting and interaction of the wall rocks with the intrusions gave rise to new magmas that crystallized zircon as new grains and overgrowths on xenocrysts. The ages of the intrusions can be determined by dating this newly crystallized zircon. The method is applied to three intrusions that present different degrees of complexity, related to age differences between intrusion and country rocks, and the effects of post-intrusive metamorphism. By careful study of cathodoluminescent images and selection of ion probe spots in zircon grains, we show that this approach is a powerful tool for obtaining accurate and precise ages. In the contact melts around the 916 ± 11 Ma Hakefjorden Complex, Pb-loss occurred in some U-rich parts of xenocrystic zircon due to the heat from the intrusion. In back-veins of the 1624 ± 6 Ma Olstorp intrusion we succeeded in geochemically distinguishing new magmatic from xenocrystic zircon despite small age differences. At Borås the mafic intrusion mixed with country rock granite to form a tonalite in which new zircon grew at 1674 ± 8 Ma. Reworking of zircon occurred during 930+33/–34 Ma upper amphibolite facies Sveconorwegian metamorphism. Pb-loss was the result of re-equilibration with metamorphic fluids. REE-profiles show consistent differences between xenocrystic, magmatic, and metamorphic zircon in all cases. They typically differ in Lu/LaN, Ce/Ce*, and Eu/Eu*, and igneous zircon with marked positive Ce/Ce* and negative Eu/Eu* lost its anomalies during metamorphism.
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