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Sökning: WFRF:(Smith Martyn T.)

  • Resultat 21-23 av 23
  • Föregående 12[3]
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  • Hebels, Dennie G. A. J., et al. (författare)
  • Performance in omics analyses of blood samples in long-term storage : opportunities for the exploitation of existing biobanks in environmental health research
  • 2013
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:4, s. 480-487
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: The suitability for omic analysis of biosamples collected in previous decades and currently stored in biobanks is unknown.</p><p>Objectives: We evaluated the influence of handling and storage conditions of blood-derived biosamples on transcriptomic, epigenomic (CpG methylation), plasma metabolomic [UPLC-ToFMS (ultra performance liquid chromatography-time-of-flight mass spectrometry)], and wide-target proteomic profiles.</p><p>Methods: We collected fresh blood samples without RNA preservative in heparin, EDTA, or citrate and held them at room temperature for ≤ 24 hr before fractionating them into buffy coat, erythrocytes, and plasma and freezing the fractions at -80oC or in liquid nitrogen. We developed methodology for isolating RNA from the buffy coats and conducted omic analyses. Finally, we analyzed analogous samples from the EPIC-Italy and Northern Sweden Health and Disease Study biobanks.</p><p>Results: Microarray-quality RNA could be isolated from buffy coats (including most biobank samples) that had been frozen within 8 hr of blood collection by thawing the samples in RNA preservative. Different anticoagulants influenced the metabolomic, proteomic, and to a lesser extent transcriptomic profiles. Transcriptomic profiles were most affected by the delay (as little as 2 hr) before blood fractionation, whereas storage temperature had minimal impact. Effects on metabolomic and proteomic profiles were noted in samples processed ≥ 8 hr after collection, but no effects were due to storage temperature. None of the variables examined significantly influenced the epigenomic profiles. No systematic influence of time-in-storage was observed in samples stored over a period of 13-17 years.</p><p>Conclusions: Most samples currently stored in biobanks are amenable to meaningful omics analysis, provided that they satisfy collection and storage criteria defined in this study.</p>
  • La Merrill, Michele A, et al. (författare)
  • Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification.
  • 2020
  • Ingår i: Nature Reviews Endocrinology. - 1759-5029 .- 1759-5037. ; 16:1, s. 45-57
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.</p>
  • McCloskey, Conor, et al. (författare)
  • Kv1.3 is the exclusive voltage-gated K plus channel of platelets and megakaryocytes: roles in membrane potential, Ca2+signalling and platelet count
  • 2010
  • Ingår i: Journal of Physiology. - The Physiological Society. - 1469-7793. ; 588:9, s. 1399-1406
  • Tidskriftsartikel (refereegranskat)abstract
    • A delayed rectifier voltage-gated K+ channel (Kv) represents the largest ionic conductance of platelets and megakaryocytes, but is undefined at the molecular level. Quantitative RT-PCR of all known Kv alpha and ancillary subunits showed that only Kv1.3 (KCNA3) is substantially expressed in human platelets. Furthermore, megakaryocytes from Kv1.3-/- mice or from wild-type mice exposed to the Kv1.3 blocker margatoxin completely lacked Kv currents and displayed substantially depolarised resting membrane potentials. In human platelets, margatoxin reduced the P2X(1)- and thromboxaneA(2) receptor-evoked [Ca2+](i) increases and delayed the onset of store-operated Ca2+ influx. Megakaryocyte development was normal in Kv1.3-/- mice, but the platelet count was increased, consistent with a role of Kv1.3 in apoptosis or decreased platelet activation. We conclude that Kv1.3 forms the Kv channel of the platelet and megakaryocyte, which sets the resting membrane potential, regulates agonist-evoked Ca2+ increases and influences circulating platelet numbers.
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  • Resultat 21-23 av 23
  • Föregående 12[3]
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Smith, Martyn T., (14)
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