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Ullerås, Erik
Alternative names
Publications (10 of 26) Show all publications
Arvidsson, P. I., Domeij, B., Hansson, M. G., Landegren, U., Lind, A.-S. & Ullerås, E. (2015). Öppenheten förstör chansen till patent. Svenska dagbladet
Open this publication in new window or tab >>Öppenheten förstör chansen till patent
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2015 (Swedish)In: Svenska dagbladet, ISSN 2001-3868Article in journal, News item (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
Stockholm: Svenska Dagbladet AB & Co., 2015
National Category
Law (excluding Law and Society)
Identifiers
urn:nbn:se:uu:diva-256305 (URN)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2017-02-08Bibliographically approved
Mattsson, A., Ullerås, E., Patring, J. & Oskarsson, A. (2012). Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test. Reproductive Toxicology, 34(1), 31-42
Open this publication in new window or tab >>Albendazole causes stage-dependent developmental toxicity and is deactivated by a mammalian metabolization system in a modified zebrafish embryotoxicity test
2012 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 34, no 1, p. 31-42Article in journal (Refereed) Published
Abstract [en]

The zebrafish embryotoxicity test has previously been combined with an external metabolic activation system (MAS) to assess developmental toxicity of metabolites produced by maternal metabolism. Due to toxicity of MAS the exposure was limited to one early and short period. We have modified the method and included additional testing time points with extended exposure durations. Using the anthelmintic drug albendazole as a model substance, we demonstrated stage-dependent toxic effects at three windows of zebrafish embryo development, i.e. 2-3, 12-14 and 24-28h post fertilization, and showed that MAS, by metabolic deactivation, reduced the toxicity of albendazole at all time points. Chemical analysis confirmed that albendazole was efficiently metabolized by MAS to the corresponding sulfoxide and sulfone, which are non-toxic to zebrafish embryos. To conclude, the modified zebrafish embryotoxicity test with MAS can be expanded for assessment of metabolites at different developmental stages.

National Category
Other Biological Topics
Identifiers
urn:nbn:se:uu:diva-171125 (URN)10.1016/j.reprotox.2012.02.007 (DOI)000305303600005 ()22414603 (PubMedID)
Available from: 2012-03-15 Created: 2012-03-15 Last updated: 2017-12-07Bibliographically approved
Westerberg, C. M., Ullerås, E. & Nilsson, G. (2012). Differentiation of mast cell subpopulations from mouse embryonic stem cells. JIM - Journal of Immunological Methods, 382(1-2), 160-166
Open this publication in new window or tab >>Differentiation of mast cell subpopulations from mouse embryonic stem cells
2012 (English)In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 382, no 1-2, p. 160-166Article in journal (Refereed) Published
Abstract [en]

Mast cells can generally be divided into two major groups, connective tissue mast cells and mucosal mast cells. We and others have previously shown that these mast cell populations can be developed in vitro from mouse bone marrow stem cells using a combination of specific growth factors and cytokines. Mast cell differentiation from mouse embryonic stem (ES) cells is an important alternative method when developing mast cells from an embryonic lethal genetic deficiency or to reduce the use and handling of experimental animals. In this study, we have used protocols prior known to induce connective tissue like mast cells (CTLMC) (SCF and IL-4) and mucosal like mast cells (MLMC) (SCF, IL-3, IL-9 and TGF-β) from mouse bone marrow progenitor cells and employed these protocols to study if phenotype specific mast cells can be developed from ES cells. We here demonstrate that mast cells of the different phenotypes, CTLMC and MLMC, can be derived from mouse ES cells. The mast cell populations were characterized by chymase expression, receptor expression and their difference in activation pattern and in activation-induced survival.

Keywords
cytosolic diffusion, single particle tracking, photoactivated localization microscopy, stroboscopic illumination
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-176860 (URN)10.1016/j.jim.2012.05.020 (DOI)000307088700016 ()22683543 (PubMedID)
Available from: 2012-06-26 Created: 2012-06-26 Last updated: 2017-12-07Bibliographically approved
Landegren, U., Vänelid, J., Hammond, M., Nong, R. Y., Wu, D., Ullerås, E. & Kamali-Moghaddam, M. (2012). Opportunities for sensitive plasma proteome analysis. Analytical Chemistry, 84(4), 1824-1830
Open this publication in new window or tab >>Opportunities for sensitive plasma proteome analysis
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2012 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 4, p. 1824-1830Article in journal (Refereed) Published
Abstract [en]

Despite great interest, investments, and efforts, the ongoing search for plasma protein biomarkers for disease so far has come up surprisingly empty-handed. While discovery programs have revealed large numbers of biomarker candidates, the clinical utility has been validated for only a very small number of these. While this disappointing state of affairs may suggest that plasma protein biomarkers have little more to offer for diagnostics, we take the perspective that experimental conditions might not have been optimal, and that analyses will be required that offer far greater sensitivity than currently available, in terms of numbers of molecules needed for unambiguous detection. Accordingly, techniques are needed to search deep and wide for protein biomarker candidates. The requirements and feasibility of such assays will be discussed.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-167983 (URN)10.1021/ac2032222 (DOI)000300470800006 ()22248085 (PubMedID)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2018-01-12Bibliographically approved
Carlsson, G., Patring, J., Ullerås, E. & Oskarsson, A. (2011). Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos.. Reproductive Toxicology, 32(1), 129-37
Open this publication in new window or tab >>Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos.
2011 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 32, no 1, p. 129-37Article in journal (Refereed) Published
Abstract [en]

Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3μM. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-161172 (URN)10.1016/j.reprotox.2011.05.015 (DOI)21683134 (PubMedID)
Available from: 2011-11-08 Created: 2011-11-08 Last updated: 2018-01-12
Ohrvik, H., Ullerås, E., Oskarsson, A. & Tallkvist, J. (2011). Effects of cadmium on calcium transporter SPCA, calcium homeostasis and β-casein expression in the murine mammary epithelium.. Toxicology Letters, 201(1), 80-5
Open this publication in new window or tab >>Effects of cadmium on calcium transporter SPCA, calcium homeostasis and β-casein expression in the murine mammary epithelium.
2011 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 201, no 1, p. 80-5Article in journal (Refereed) Published
Abstract [en]

Maternal cadmium (Cd) exposure during lactation causes neurobehavioral effects in the suckling offspring as well as involution like disturbances in the mammary glands of rodents. The aim of the present study was to examine Cd-induced effects in secreting mammary epithelial cells in relation to calcium (Ca) transport and β-casein expression. Reduced protein expression of secretory pathway Ca-ATPase (SPCA) was revealed in the mammary glands of lactating mice exposed to Cd during peak lactation. In concordance, SPCA gene expression was down regulated and total intracellular Ca levels reduced in murine mammary epithelial HC11 cells treated with Cd for 72 h. Cd reduced β-casein gene expression in a concentration dependent manner in the HC11 cells. Our findings on Cd-induced reduction of Ca levels, SPCA and β-casein expression in the mammary epithelium resemble the effects observed in the mammary glands as a result of forced weaning. In conclusion, maternal Cd exposure during lactation may disturb Ca regulation and decrease the levels of β-casein in milk with potential nutritional and developmental implications for the breast-fed newborn.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-161174 (URN)10.1016/j.toxlet.2010.12.008 (DOI)21167921 (PubMedID)
Available from: 2011-11-09 Created: 2011-11-08 Last updated: 2017-12-08
Haldén, A. N., Arnoldsson, K., Haglund, P., Mattsson, A., Ullerås, E., Sturve, J. & Norrgren, L. (2011). Retention and maternal transfer of brominated dioxins in zebrafish (Danio rerio) and effects on reproduction, aryl hydrocarbon receptor-regulated genes, and ethoxyresorufin-O-deethylase (EROD) activity.. Aquatic Toxicology, 102(3-4), 150-61
Open this publication in new window or tab >>Retention and maternal transfer of brominated dioxins in zebrafish (Danio rerio) and effects on reproduction, aryl hydrocarbon receptor-regulated genes, and ethoxyresorufin-O-deethylase (EROD) activity.
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2011 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 102, no 3-4, p. 150-61Article in journal (Refereed) Published
Abstract [en]

Brominated dioxins have recently been detected in Baltic Sea biota. Due to their similarities to the highly toxic chlorinated dioxins, concern has been raised about their potential biological effects. The present study investigated retention and effects of brominated dioxins in adult zebrafish, as well as maternal transfer and effects on offspring. We exposed adult zebrafish for nine weeks via feed to 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) or to a mixture of brominated dioxins (Baltic Sea mixture), which was designed to reflect relative concentrations found in Baltic Sea biota. We studied spawning success, gonad morphology, hepatic vitellogenin gene expression, and offspring early life-stage development to investigate effects on zebrafish reproduction. Hepatic ethoxyresorufin-O-deethylase (EROD) activity and hepatic expression of a number of aryl hydrocarbon receptor (AHR)-regulated genes were studied to investigate if the brominated dioxins can activate gene transcription through the AHR pathway in zebrafish. In addition, glutathione reductase activity and expression of genes involved in adaptive responses to intracellular stress were studied to investigate potential stress effects of brominated dioxins. After nine weeks of exposure, all brominated dioxins spiked to the feed were detected in female fish and transferred to eggs. Exposure to the Baltic Sea mixture and TBDD clearly induced AHR-regulated genes and EROD activity. Exposure to TBDD reduced spawning success, altered ovarian morphology and reduced hepatic vitellogenin gene expression, which implies that TBDD has a similar effect pattern as the chlorinated analogue. Overall, our results show that dietary exposure to sublethal concentrations of brominated dioxins may impair reproductive physiology in fish and induce AHR-regulated genes.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-161173 (URN)10.1016/j.aquatox.2011.01.008 (DOI)21356177 (PubMedID)
Available from: 2011-11-09 Created: 2011-11-08 Last updated: 2017-12-08
Asp, V., Ullerås, E., Lindström, V., Bergström, U., Oskarsson, A. & Brandt, I. (2010). Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells. Toxicology and Applied Pharmacology, 242(3), 281-289
Open this publication in new window or tab >>Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells
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2010 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 242, no 3, p. 281-289Article in journal (Refereed) Published
Abstract [en]

The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO(2)-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects. 3-MeSO(2)-DDE is bioactivated by cytochrome P450 (CYP) 11B1 in mice and causes formation of irreversibly bound protein adducts, reduced glucocorticoid secretion, and cell death in the adrenal cortex of several animal species. The present study was carried out to assess similarities and differences between mice and humans concerning the adrenocorticolytic effects of 3-MeSO(2)-DDE. The results support previous indications that humans are sensitive to the adrenocorticolytic actions of 3-MeSO(2)-DDE by demonstrating protein adduct formation and cytotoxicity in the human adrenocortical cell line H295R. However, neither the irreversible binding nor the cytotoxicity of 3-MeSO(2)-DDE in H295R cells was inhibited by the CYP11B1 inhibitor etomidate. We also report biphasic responses to 3-MeSO(2)-DDE in cortisol and aldosterone secretion as well as in mRNA levels of the steroidogenic genes StAR, CYP11B1 and CYP11B2. Hormone levels and mRNA levels were increased at lower concentrations of 3-MeSO(2)-DDE, while higher concentrations decreased hormone levels. These biphasic responses were not observed with o,p'-DDD or with the precursor DDT metabolite p,p'-DDE. Based on these results, 3-MeSO(2)-DDE remains a viable lead compound for drug design, although the adrenocorticolytic effects of 3-MeSO(2)-DDE in human cells seem more complex than in murine cells.

Keywords
Adrenocorticolytic DDT metabolites, Endocrine disruption, Adrenocortical cancer (ACC), Biphasic responses, Steroidogenesis, H295R
National Category
Pharmacology and Toxicology
Research subject
Ecotoxicology
Identifiers
urn:nbn:se:uu:diva-112583 (URN)10.1016/j.taap.2009.10.018 (DOI)000273832500006 ()19900470 (PubMedID)
Available from: 2010-01-15 Created: 2010-01-15 Last updated: 2018-01-12
Gulliksson, M., Carvalho, R. F., Ullerås, E. & Nilsson, G. (2010). Mast cell survival and mediator secretion in response to hypoxia.. PloS one, 5(8), e12360
Open this publication in new window or tab >>Mast cell survival and mediator secretion in response to hypoxia.
2010 (English)In: PloS one, ISSN 1932-6203, Vol. 5, no 8, p. e12360-Article in journal (Refereed) Published
Abstract [en]

Tissue hypoxia is a consequence of decreased oxygen levels in different inflammatory conditions, many associated with mast cell activation. However, the effect of hypoxia on mast cell functions is not well established. Here, we have investigated the effect of hypoxia per se on human mast cell survival, mediator secretion, and reactivity. Human cord blood derived mast cells were subjected to three different culturing conditions: culture and stimulation in normoxia (21% O(2)); culture and stimulation in hypoxia (1% O(2)); or 24 hour culture in hypoxia followed by stimulation in normoxia. Hypoxia, per se, did not induce mast cell degranulation, but we observed an increased secretion of IL-6, where autocrine produced IL-6 promoted mast cell survival. Hypoxia did not have any effect on A23187 induced degranulation or secretion of cytokines. In contrast, cytokine secretion after LPS or CD30 treatment was attenuated, but not inhibited, in hypoxia compared to normoxia. Our data suggests that mast cell survival, degranulation and cytokine release are sustained under hypoxia. This may be of importance for host defence where mast cells in a hypoxic tissue can react to intruders, but also in chronic inflammations where mast cell reactivity is not inhibited by the inflammatory associated hypoxia.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-161175 (URN)10.1371/journal.pone.0012360 (DOI)20808808 (PubMedID)
Available from: 2011-11-09 Created: 2011-11-08 Last updated: 2011-11-09
Ohlsson, A., Ullerås, E., Cedergreen, N. & Oskarsson, A. (2010). Mixture effects of dietary flavonoids on steroid hormone synthesis in the human adrenocortical H295R cell line.. Food and Chemical Toxicology, 48(11), 3194-200
Open this publication in new window or tab >>Mixture effects of dietary flavonoids on steroid hormone synthesis in the human adrenocortical H295R cell line.
2010 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 48, no 11, p. 3194-200Article in journal (Refereed) Published
Abstract [en]

Humans are exposed to a mixture of dietary flavonoids with a variety of potential beneficial and harmful effects. Flavonoids are endocrine disruptors, acting both at receptor level and by interfering with steroid hormone synthesis. Due to a high dietary intake and the potential to cause mixture effects, assessment of combined exposure of flavonoids is required. We have studied effects on cortisol, aldosterone, testosterone and oestradiol secretion of the individual isoflavones daidzein and genistein, the flavone apigenin and the mixture of the three flavonoids in human adrenocortical H295R cells. The most vulnerable targets of the flavonoids were the secretion of cortisol and testosterone, which were inhibited by daidzein and genistein with IC50 values below 1 μM. An equimolar mixture of the flavonoids caused inhibition of cortisol, aldosterone and testosterone secretion in an additive manner. The observed mixture effect was described well by both concentration addition (CA) and independent action (IA) prediction models. Both prediction models underestimated the effect on oestradiol secretion. We conclude that the three flavonoids exhibit specific effects on steroid hormone secretion. A mixture of the flavonoids caused additive effects emphasizing the need to assess flavonoids together as a group. The prediction models are valuable tools for mixture assessment.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-161176 (URN)10.1016/j.fct.2010.08.021 (DOI)20732377 (PubMedID)
Available from: 2011-11-09 Created: 2011-11-08 Last updated: 2017-12-08
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