| 1. |
- Broberg Palmgren, Karin, et al.
(författare)
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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.
- 2010
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Ingår i: Pharmacogenetics & Genomics. - 1744-6872 .- 1744-6880. ; 20:2, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.
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| 2. |
- Grinnemo, Karl-Henrik, et al.
(författare)
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Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart
- 2008
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 26:7, s. 1850-1857
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Tidskriftsartikel (refereegranskat)abstract
- In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.
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| 3. |
- Arnrup, K, et al.
(författare)
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Classification of dental behavior management problems among children.
- 2007
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Ingår i: Poster presentation at the 85th General Session & Exhibition of the IADR, New Orleans, LA, USA, March 21-24, 2007..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: This study aimed to further investigate the heterogeneity within the group of children referred for specialist treatment because of dental behavior management problems (DBMP). A specific aim was to evaluate the validity of a previously reported cluster structure in another DBMP study group. Methods: 177 child dental patients, aged 4 to 12 at referral to a specialist pediatric dental clinic in Göteborg, Sweden, were classified into subgroups according to their personal characteristics. Cluster structure was described and compared to previously reported findings in a DBMP study group of same-aged child dental patients in Örebro, Sweden (n=74). Parental assessments of children's dental and general fear, temperament and behavior were made pre-treatment. The children also performed a vocabulary test. Data were analyzed mainly with a person-based approach using sequences of cluster analyses. Results: Classification into five different subgroups was judged the best representation of the Göteborg study group data, while four groups had been defined in Örebro. The new clusters partly paralleled the previous and were labeled (I) Extrovert, outgoing, (II) Highly fearful, multiple problems, (III) Highly fearful, (IV) Moderately fearful, externalizing, impulsive and (V) Moderately fearful, inhibited. Cluster profile II describes severe dental fear and general temperamental and behavioral problems of internalizing as well as externalizing character. Such combined problems were not clearly revealed in the Örebro cluster structure. Conclusion: The contention that children with dental behavior management problems (DBMP) comprise a heterogeneous group was strengthened. Similar, although not identical, clusters of children showing DBMP were identified in this replication study. Apart from different levels of dental fear, varying temperamental and behavioral characteristics need to be taken into consideration to better match treatment for these patients
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| 4. |
- Asp, Michaela, et al.
(författare)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 5. |
- Benderix, Ylva, 1953-, et al.
(författare)
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Barn med neuropsykiatriskt funktionshinder
- 2009
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Ingår i: PEDIATRISK OMVÅRDNAD. - Stockholm : LIBER. - 9789147093274 ; , s. 309-315
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Benser, Jasmin, et al.
(författare)
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Impact of physical activity and cardiovascular fitness on total homocysteine concentrations in European adolescents : The HELENA study
- 2015
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Ingår i: Journal of Nutritional Science and Vitaminology. - : Center for Academic Publications Japan. - 0301-4800 .- 1881-7742. ; 61:1, s. 45-54
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8±1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.0 5) with CVF in females (measured both by stages: r=-0.118 and by VO 2 max: r=-0.10 2) and positively with body mass index (r=0.10 0). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.0 5). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.
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| 7. |
- Broberg, Agneta Månsson
(författare)
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Myocardial angiogenesis : aspects on endogenous determinants and effects of stimulation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Therapeutic angiogenesis using i.e. VEGF and FGF have shown beneficial effects, however, delivery routes and other modulating agents have not been thoroughly investigated. In this study the efficacy of adenovirus gene transfer was compared to plasmid gene transfer. The angiogenic effects of ephrinB2 were explored, as were the cardioprotective effects of erythropoietin and estrogen, with angiogenic effects in focus. Since hypoxia is the key regulator of angiogenesis, the studies were performed in an ischemic setting with a myocardial infarction model. Results: Intramyocardial AdhVEGF-A165 transfer induced higher hVEGF-A protein expression than PhVEGF-A165 in rat myocardium (p<0.001). PhVEGF- A165 and AdhVEGF-A165 stimulated angiogenesis and improved left ventricular function to similar extent. AdhVEGFA165 induced more apoptotic cells (p<0.001) and higher ectopic expression of VEGF-A165 than PhVEGF-A165 gene transfer. Treatment with darbepoietin-alpha did not alter capillary density after myocardial infarction in a mouse myocardial infarction model. Cell proliferation was higher in the periinfarct area compared to the non infarcted area. Darbepoietin-alpha treatment gave a decreased cell proliferation (BrdU, p< 0.02) and apoptosis (TUNEL, p<0.005) with 30% in the periinfarct area. Darbepoietin-alpha and VEGF-A165 both induced angiogenic sprouting from cultured murine aortic rings. The ephrin/Eph system was expressed in murine myocardium and altered as regards the ephrinB2/EphB4 expression after myocardial infarction (p<0.005). Modulation of ephrinB2 with fusion protein tended to increase mitosis, measured by BrdU incorporation in the periinfarct area, and also increased capillary density in the periinfarct area. EphrinB2 induced proliferation in human aortic endothelial cells (p<0.0005) and aortic ring sprouting (p<0.05) to a similar extent as VEGF-A165. In ERbetaKO mice the downregulation of ERalpha and the absence of functional ERbeta and in ERalphaKO the absence of functional ERalpha and the downregulation of ERbeta did not influence myocardial angiogenesis or arteriogenesis after myocardial infarction. In the periinfarct area of ERalphaKO mice the number of macrophages was lower compared to control (p<0.05). Conclusions: AdhVEGF-A165 does not have any obvious superior angiogenic efficacy compared to PhVEGF-A165 but more side effects in a rat myocardial infarction model. Darbepoietin-alpha induces endothelial sprouting in a murine aortic ring culture, but in this model darbepoietin-alpha decreases cell proliferation and apoptosis in the periinfarct area with capillary and arteriolar densities unchanged. The ephrin/Eph system is present in the myocardium, and alters after myocardial infarction. EphrinB2 Fc tends to increase the mitotic activity and prevents a decrement in capillary density in the periinfarct area. Also ephrinB2 Fc induces endothelial cell proliferation in vitro, and stimulates angiogenic sprouting in an aortic ring model. mRNA expression of estrogen receptors are present in the myocardium. After myocardial infarction in ERbetaKO ERalpha mRNA and in ERalphaKO ERbeta mRNA are downregulated, without any influence on angiogenesis or arteriogenesis.
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| 8. |
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| 9. |
- Broberg Palmgren, Karin, et al.
(författare)
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Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study
- 2008
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Ingår i: Environmental Health. - 1476-069X. ; 7:15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways.
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| 10. |
- Dalen, Magnus, et al.
(författare)
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Percutaneous Fluoroscopic-Guided Endomyocardial Delivery in an Experimental Model of Left Ventricular Assist Device Support
- 2015
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Ingår i: Journal of Cardiovascular Translational Research. - : Springer Science and Business Media LLC. - 1937-5387 .- 1937-5395. ; 8:6, s. 381-384
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Tidskriftsartikel (refereegranskat)abstract
- Endomyocardial delivery in the setting of active left ventricular assist device (LVAD) support has rarely been studied. The objective was to establish a protocol for endomyocardial injections during LVAD support without compromising mechanical circulation. LVAD implantation was performed in four pigs. A curved needle catheter was percutaneously inserted into the right carotid artery and positioned into the left ventricle under fluoroscopic guidance. In the setting of increasing LVAD flows (2.3-3.1 l/min), percutaneous methylene blue dye administration into the myocardium proceeded without complications in all pigs. Transection of excised hearts revealed an anterior, lateral, inferior, and septal wall distribution of methylene blue documenting injections in all four regions of the left ventricle. Ex vivo, the catheter could be maneuvered close to the LVAD inflow cannula despite augmentation of LVAD flow up to 5 l/min. Endomyocardial injections during LVAD support was found to be feasible and safe with the curved needle catheter.
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