Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-23T12:34:55.987Z Has data issue: false hasContentIssue false
  • English
  • Français

Life Science Applications Utilizing Radiocarbon Tracing

Published online by Cambridge University Press:  09 February 2016

M Salehpour ,
K Håkansson ,
P Westermark ,
G Antoni ,
G Wikström  and
G Possnert
M Salehpour*
Affiliation:
Department of Physics and Astronomy, Applied Nuclear Physics Division, Ion Physics, PO Box 516, SE-751 20 Uppsala, Sweden
K Håkansson
Affiliation:
Department of Physics and Astronomy, Applied Nuclear Physics Division, Ion Physics, PO Box 516, SE-751 20 Uppsala, Sweden
P Westermark
Affiliation:
Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden
G Antoni
Affiliation:
PET-Centre, Centre for Medical Imaging, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
G Wikström
Affiliation:
Department of Medical Sciences, Cardiology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
G Possnert
Affiliation:
Department of Physics and Astronomy, Applied Nuclear Physics Division, Ion Physics, PO Box 516, SE-751 20 Uppsala, Sweden
*
Corresponding author: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Radiocarbon-based accelerator mass spectrometry (AMS) facilities at Uppsala University include a measurement center for archaeological applications and a separate entity dedicated to life science research. This paper addresses the latter, with the intention of giving a brief description of the biomedical activities at our laboratory, as well as presenting new data. The ultra-small sample preparation method, which can be used down to a few μg C samples, is outlined and complemented with new results. Furthermore, it is shown that the average secondary ion current performance for small samples can be improved by increasing the distance between the cathode surface and the pressed graphite surface. Finally, data is presented for a new application: Amyloidoses are a group of diseases where the conformational changes in specific proteins' structure lead to the formation of extracellular deposits that spread and increase in mass and eventually may lead to total organ failure and death. The formation timeframe is unknown and yet it is an important clue for the elucidation of the mechanism. We present results on bomb-peak dating of 4 different types of purified amyloid proteins from human postmortem heart and spleen samples. The data indicates that the average measured age of the carbon originating from the systemic amyloid types studied here correspond to a few years before the death of the subject. This suggests that a major part of the fibril formation takes place during the last few years before death, rather than as an accumulation of amyloid deposits over decades.

Type
Articles
Information
Radiocarbon , Volume 55 , Issue 2: Proceedings of the 21st International Radiocarbon Conference (Part 1 of 2) , 2013 , pp. 865 - 873
Copyright
Copyright © 2013 by the Arizona Board of Regents on behalf of the University of Arizona 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alkass, K, Buchholz, BA, Druid, D, Spalding, KL. 2009. Analysis of 14C and 13C in teeth provides precise birth dating and clues to geographical origin. Forensic Science 209(1–3):34–41.Google Scholar
Arner, P, Bernard, S, Salehpour, M, Possnert, G, Liebl, J, Steier, P, Buchholz, BA, Eriksson, M, Arner, E, Hauner, H, Skurk, T, Rydén, M, Frayn, KN, Spalding, KL. 2011. Dynamics of human adipose lipid turnover in health and metabolic disease. Nature 478(7367):110–3.Google Scholar
Bergmann, O, Bhardwaj, RD, Bernard, S, Zdunek, S, Barnabe-Heider, F, Walsh, S, Zupicich, J, Buchholz, B, Druid, H, Jovinge, S, Frisén, J. 2009. Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102.CrossRefGoogle ScholarPubMed
Bernard, S, Frisen, J, Spalding, KL. 2010. A mathematical model for the interpretation of nuclear bomb test derived 14C incorporation in biological systems. Nuclear Instruments and Methods in Physics Research B 268(7–8):1295–8.Google Scholar
Hägg, S, Salehpour, M, Noori, P, Lundström, J, Possnert, G, Takolander, R, Konrad, P, Rosfors, S, Ruusalepp, A, Skogsberg, J, Tegnér, J, Björkegren, J. 2011. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin. PLoS ONE 6(4):e18248.Google Scholar
Hua, Q, Zoppi, U, Williams, AA, Smith, AM. 2004. Smallmass AMS radiocarbon analysis at ANTARES. Nuclear Instruments and Methods in Physics Research B 223–224:284–92.CrossRefGoogle Scholar
Lappin, G, Garner, C. 2003. Big physics, small doses: the use of AMS and PET in human microdosing of development drugs. Nature Reviews, Drug Discovery 2(3):223–40.Google Scholar
Levin, I, Kromer, B. 2004. The tropospheric 14CO2 level in mid latitudes of the Northern Hemisphere. Radiocarbon 46(3):1261–72.CrossRefGoogle Scholar
Lovell, MA, Robertson, JD, Buchholz, BA, Xie, C, Markesbery, WR. 2002. Use of bomb-pulse carbon-14 to age senile plaques and neurofibrillary tangles in the Alzheimer's disease. Neurobiology of Aging 23(2):179–186.Google Scholar
Luheshi, LM, Dobson, CM. 2009. Bridging the gap: from protein misfolding to protein misfolding diseases. FEBS Letters 583(16):2581–6.CrossRefGoogle Scholar
Merlini, G, Westermark, P. 2004. The systemic amyloidoses: clearer understanding of the molecular mechanisms offers hope for more effective therapies. Journal of Internal Medicine 255(2):159–78.Google Scholar
Middleton, R. 1989. A Negative Ion Cookbook. Department of Physics, University of Pennsylvania, Pennsylvania 19104, USA. Revised February 1990.Google Scholar
Sadiq, M, Salehpour, M, Forsgård, N, Possnert, G, Hammarlund-Udenaes, M. 2011. Morphine brain pharmacokinetics at very low concentrations studied with accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry. Drug Metabolism and Disposition 39(2):174–9.Google Scholar
Salehpour, M, Possnert, G, Bryhni, H. 2008. Subattomole sensitivity in biological accelerator mass spectrometry. Analytical Chemistry 80(10):3515–21.CrossRefGoogle ScholarPubMed
Salehpour, M, Forsgard, N, Possnert, G. 2008. Accelerator mass spectrometry of small biological samples. Rapid Communications in Mass Spectrometry 22(23):3928–34.Google Scholar
Salehpour, M, Forsgard, N, Possnert, G. 2009. FemtoMolar measurements using accelerator mass spectrometry. Rapid Communications in Mass Spectrometry 23(5):557–63.CrossRefGoogle ScholarPubMed
Salehpour, M, Håkansson, K, Possnert, G. 2013. Accelerator mass spectrometry of ultra-small samples with applications in the biosciences. Nuclear Instruments and Methods in Physics Research B 294:97–103.Google Scholar
Salehpour, M, Håkansson, K, Höglund, U, Grahn-Westin, A, Nilsson, S, Márquez, M, Possnert, G, Holmberg, AR. 2011. Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate. Rapid Communications in Mass Spectrometry 25(17):2453–8.Google Scholar
Santos, GM, Southon, JR, Griffin, S, Beaupré, SR, Druffel, ERM. 2007. Ultra small-mass 14C-AMS sample preparation and analysis at the KCCAMS Facility. Nuclear Instruments and Methods in Physics Research B 259(1):293–302.CrossRefGoogle Scholar
Spalding, KL, Buchholz, BA, Bergman, LE, Druid, H, Frisén, J. 2005. Forensics: age written in teeth by nuclear tests. Nature 437(7057):333–4.Google Scholar
Southon, J, Santos, G, Han, B. 2007. Cs feed test and emittance measurements on a modified MC-SNICS ion source for radiocarbon AMS. Radiocarbon 49(2):301–6.Google Scholar
Spalding, KL, Bergmann, O, Alkass, K, Bernard, S, Salehpour, M, Huttner, HB, Boström, E, Westerlund, I, Vial, C, Buchholz, BA, Possnert, P, Mash, DX, Druid, H, Frisen, J. 2013. Dynamics of hippocampal neurogenesis in adult humans. Cell 153(6):1219–27.CrossRefGoogle ScholarPubMed
Spalding, KL, Arner, E, Westermark, PO, Bernard, S, Buchholz, BA, Bergmanm, O, Blomqvist, L, Hoffstedt, J, Näslund, E, Britton, T, Concha, H, Hassan, M, Rydén, M, Frisén, J, Arner, P. 2008. Dynamics of fat cell turnover in humans. Nature 453(7196):783–7.Google Scholar
Stuiver, M, Quay, PD. 1981. Atmospheric 14C changes resulting from fossil fuel CO2 release and cosmic ray flux variability. Earth and Planetary Science Letters 53(3):349–63.Google Scholar
Synal, H-A, Stocker, M, Suter, M. 2007. MICADAS: a new compact radiocarbon AMS system. Nuclear Instruments and Methods in Physics Research B 259(1):7–13.CrossRefGoogle Scholar
Turteltaub, KW, Felton, JS, Gledhill, BL, Vogel, JS, Southon, JR, Caffee, MW, Finkel, RC, Nelson, DE, Proctor, ID, Davis, JC. 1990. Accelerator mass spectrometry in biomedical dosimetry: relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA. Proceedings of the National Academy of Sciences of the USA 87(14):5288–92.CrossRefGoogle ScholarPubMed
Yokoyama, Y, Koizumi, M, Matzusaki, H, Miyairi, Y. 2010. Developing ultra small-scale radiocarbon sample measurement at the University of Tokyo. Radiocarbon 52(2–3):310–8.Google Scholar
Westermark, GT, Westermark, P. 2005. Purification of amyloid protein AA subspecies from amyloid-rich human tissues. Methods in Molecular Biology 299:243–54.Google Scholar