| 1. |
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| 2. |
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| 3. |
- Ceberg, Crister, et al.
(author)
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Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.
- 2012
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In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:24, s. 8377-8391
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Journal article (peer-reviewed)abstract
- 75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.
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| 4. |
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| 6. |
- Frennby, Bo, et al.
(author)
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Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques
- 1997
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 57:3, s. 241-252
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Journal article (peer-reviewed)abstract
- In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing "dose of marker" with "area under the plasma concentration curve" (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)-our reference method representing the "true" GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the median overestimation of the "true" GFR with Clprovisional was higher when "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the "true" GFR from 1.9 to 1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a "late" plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.
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| 7. |
- Frennby, Bo, et al.
(author)
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Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques
- 1996
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In: Academic Radiology. - 1878-4046. ; 3:8, s. 651-659
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker
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| 8. |
- Frennby, Bo, et al.
(author)
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Extrarenal plasma clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and inulin in anephric pigs
- 1996
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In: Academic Radiology. - 1878-4046. ; 3:2, s. 145-153
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Journal article (peer-reviewed)abstract
- RATIONALE AND OBJECTIVES: To improve the measurement of the glomerular filtration rate (GFR), we determined the extrarenal plasma clearance of the GFR markers iohexol, chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), and inulin using 11 anephric pigs. METHODS: After an intravenous (i.v.) bolus injection of the markers, the decay curves of their plasma concentrations were monitored for 29 hr by 16 plasma samples. The area under the curve (AUC; concentration of marker versus time) was calculated according to one- and three-compartment kinetics. The extrarenal clearance was calculated by dividing the dose of marker by the AUC. RESULTS: In the three-compartment model, the median of the extrarenal clearances of iohexol, 51Cr-EDTA, and inulin were 0.87 ml.min-1.10 kg-1 (range = 0.62-1.26 ml.min-1.10 kg-1), 0.79 ml.min-1.10 kg-1 (range = 0.61-1.04 ml.min-1.10 kg-1), and 0.83 ml.min-1.10 kg-1 (range = 0.65-1.17 ml.min-1.10 kg-1). The extrarenal clearance of 51Cr-EDTA was slightly lower than that of iohexol and inulin when measured with the three-compartment model (p = .015). There was no statistically significant difference between the two models of kinetics in calculating clearance of the same marker. CONCLUSION: Our results indicate that subtracting the median values of the extrarenal clearance of the markers from the total plasma clearance will provide GFR values closer to the "true" GFR. This technique might prove useful in GFR calculations in patients with a very low GFR (e.g., residual GFR in patients on dialysis)
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| 9. |
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| 10. |
- Jönsson, Bo, et al.
(author)
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Titrating polyelectrolytes - Variational calculations and Monte Carlo simulations
- 1996
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In: Journal of Physical Chemistry. - : American Chemical Society (ACS). - 0022-3654 .- 1541-5740. ; 100:1, s. 409-417
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Journal article (peer-reviewed)abstract
- Variational methods are used to calculate structural and thermodynamical properties of a titrating polyelectrolyte in a discrete representation. In the variational treatment, the Coulomb potentials are emulated by harmonic repulsive forces between all monomers; the force constants are used as variational parameters. The accuracy of the variational approach is tested against Monte Carlo data. Excellent agreement is obtained for the end-to-end separation and the apparent dissociation constant for the unscreened Coulomb chain. The short-range screened Coulomb potential is more difficult to handle variationally, and its structural features are less well described, although the thermodynamic properties are predicted with the same accuracy as for the unscreened chain. The number of variational parameters is on the order of N2, where N is the number of monomers, and the computational effort scales like N3. In addition, a simplified variational procedure with only two parameters is pursued, based on a rigid-rod approximation of the polymer. It gives surprisingly good accuracy for certain physical properties.
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| 11. |
- Jönsson, Bo, et al.
(author)
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Variational approach to correlations in charged polymers
- 1993
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In: Physical Review Letters. - 0031-9007. ; 71:3, s. 376-379
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Journal article (peer-reviewed)abstract
- A deterministic algorithm for calculating polymer properties is presented. It is based on a variational approach where the bond and Coulomb potentials are approximated by a quadratic trial energy. The parameters which describe average atom positions and Gaussian fluctuations, are the solutions of matrix equations. By a judicious choice of parameter representations and the use of incremental matrix inversion, an efficient iterative algorithm is constructed that is several orders of magnitude faster than Monte Carlo methods. The method is explored numerically at realistic temperatures with results that agree within 5% with those of Monte Carlo calculations.
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| 12. |
- Jönsson, Bo, et al.
(author)
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Variational approach to the structure and thermodynamics of linear polyelectrolytes with Coulomb and screened Coulomb interactions
- 1995
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In: Journal of Physical Chemistry. - : American Chemical Society (ACS). - 0022-3654 .- 1541-5740. ; 99:4, s. 1251-1266
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Journal article (peer-reviewed)abstract
- A variational approach, based on a discrete representation of the chain, is used to calculate free energy and conformational properties in polyelectrolytes. The true bond and Coulomb potentials are approximated by a trial isotropic harmonic energy containing force constants between all monomer-pairs as variational parameters. By a judicious choice of representation and the use of incremental matrix inversion, an efficient and fast-convergent iterative algorithm is constructed, that optimizes the free energy. The computational demand scales as N3 rather than N4, as expected in a more naive approach. The method has the additional advantage that in contrast to Monte Carlo calculations the entropy is easily computed. An analysis of the high- and low-temperature limits is given. Also, the variational formulation is shown to respect the appropriate virial identities. The accuracy of the approximations introduced is tested against Monte Carlo simulations for problem sizes ranging from N = 20 to 1024. Very good accuracy is obtained for chains with unscreened Coulomb interactions. The addition of salt is described through a screened Coulomb interaction, for which the accuracy in a certain parameter range turns out to be inferior to the unscreened case. The reason is that the harmonic variational Ansatz becomes less efficient with shorter range interactions. As a byproduct a very efficient Monte Carlo algorithm was developed for comparisons, providing high statistics data for very large sizes-2048 monomers. The Monte Carlo results are also used to examine scaling properties, based on low-T approximations to end-end and monomer-monomer separations. It is argued that the former increases faster than linearly with the number of bonds.
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| 13. |
- Jönsson, Lena M, et al.
(author)
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A dosimetry model for the small intestine incorporating intestinal wall activity and cross-doses.
- 2002
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In: Journal of Nuclear Medicine. - 0161-5505. ; 43:12, s. 1657-1664
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Journal article (peer-reviewed)abstract
- Current internal radiation dosimetry models for the small intestine, and for most walled organs, lack the ability to account for the activity uptake in the intestinal wall. In existing models the cross-dose from nearby loops of the small intestine is not taken into consideration. The aim of this investigation was to develop a general model for calculating the absorbed dose to the radiation-sensitive cells in the small intestinal mucosa from radionuclides located in the small intestinal wall or contents. Methods: A model was developed for calculation of the self-dose and cross-dose from activity in the intestinal wall or contents. The small intestine was modeled as a cylinder with 2 different wall thicknesses and with an infinite length. Calculations were performed for various mucus thicknesses. S values were calculated using the EGS4 Monte Carlo simulation package with the PRESTA algorithm and the simulation results were integrated over the depth of the radiosensitive cells. The cross-organ dose was calculated by summing the dose contributions from other intestinal segments. Calculations of S values for self-dose and cross-dose were made for monoenergetic electrons, 0.050–10 MeV, and for the radionuclides 99mTc, 111In, 131I, 67Ga, 90Y, and 211At. Results: The self-dose S value from activity located in the small intestinal wall is considerably greater than the S values for self-dose from the contents and the cross-dose from wall and contents except for high electron energies. For all radionuclides investigated and for electrons 0.10–0.20 MeV and 8–10 MeV in energy, the cross-dose from activity in the contents is higher than the self-dose from the contents. The mucus thickness affects the S value when the activity is located in the contents. Conclusion: A dosimetric model for the small intestine was developed that takes into consideration the localization of the radiopharmaceutical in the intestinal wall or in the contents. It also calculates the contribution from self-dose and cross-dose. With this model, more accurate calculations of absorbed dose to radiation-sensitive cells in the intestine are possible.
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| 14. |
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| 15. |
- Jönsson, Lena S, et al.
(author)
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Influence of glutathione-related genes on symptoms and immunologic markers among vulcanization workers in the southern Sweden rubber industries.
- 2008
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 81:7, s. 913-919
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim was to elucidate the role of genetic variants on symptoms of the eyes and airways, headache and nausea, as well as on immunologic markers, among vulcanization workers in the contemporary Swedish rubber industry. Polymorphisms in genes, which are involved in the defense against reactive oxygen species and metabolism of toxic substances present in the vulcanization fumes, were analyzed. METHODS: One hundred and forty-five exposed and 117 unexposed workers were included in the study. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded and immunologic markers analyzed in blood. Polymorphisms in glutathione-related genes (glutamate cysteine ligase catalytic subunit (GCLC)-129, glutamate cysteine ligase modifier subunit (GCLM)-588, glutathione S-transferase alpha 1 (GSTA1)-52, GSTM1*O, GSTP1-105, GSTP1-114, and GSTT1*O) were analyzed by Taqman-based allelic discrimination and ordinary PCR. RESULTS: A protective effect of GSTA1-52 (G/A + A/A) genotype on symptoms and immunologic cells, in particular among exposed workers, was suggested. Exposed workers with GSTT1*O had increased risk of nosebleed compared to exposed workers with GSTT1*1. Exposed workers with GSTP1-105 (ile/val + val/val) had decreased levels of total immunoglobulin E (IgE) compared to exposed workers with GSTP1-105 ile/ile. GCLC-129 variant genotype demonstrated increased levels of immunologic cells among exposed workers, although statistical significance was not reached. CONCLUSION: Our data indicate that hereditary factors influence the susceptibility to symptoms and the immunologic response of workers in the rubber industry.
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| 16. |
- Jönsson, Lena S, et al.
(author)
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Levels of 1-hydroxypyrene, symptoms and immunologic markers in vulcanization workers in the southern Sweden rubber industries.
- 2008
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 82, s. 131-137
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim of this study was to determine urinary 1-hydroxypyrene (1-HP) levels in contemporary Swedish vulcanization workers and in controls. These levels were used as an index substance for vulcanization fumes, as well as a biomarker for polycyclic aromatic hydrocarbons (PAHs). The risk of symptoms and changed levels of immunologic markers were investigated in relation to the 1-HP levels. METHODS: Included in the study were 163 exposed workers and 106 controls. Medical and occupational histories were obtained by structured interviews. Symptoms were recorded and immunologic markers analysed in blood by routine analysis methods. Levels of 1-HP were determined by liquid chromatography and fluorescence detection. RESULTS: The highest levels of 1-HP were found among exposed workers using injection and compression vulcanization and lower levels were found among exposed workers vulcanizing with salt bath, hot air, microwaves or fluid-bed. Compared to controls, exposed workers had increased risks of eye symptoms, nosebleeds, burning and dry throat, hoarseness, severe dry cough, nausea and headache. Furthermore, exposed workers had elevated levels of neutrophils and total IgG (immunoglobulin subclass G). However, only for severe dry cough an evident exposure-response relationship with urinary 1-HP levels was found. CONCLUSIONS: This work clearly shows increased levels of urinary 1-HP in Swedish vulcanization workers. Furthermore, it demonstrates an increased risk of several symptoms and elevated levels of some immunologic markers in these workers. However, no obvious exposure-response relationships were found.
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| 17. |
- Jönsson, Lena S, et al.
(author)
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Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries.
- 2007
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 80:7, s. 589-598
-
Journal article (peer-reviewed)abstract
- Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS2), which is biotransformed to 2-thiothiazolidine- 4carboxylic acid (TTCA). TTCA is used as a biomarker of CS2 exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or Xuid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.
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| 18. |
- Jönsson, Lena S, et al.
(author)
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Lung function in relation to 2-thiothiazolidine-4-carboxylic Acid and genetic effect modification among rubber workers in sweden.
- 2008
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In: Journal of Occupational and Environmental Medicine. - 1536-5948. ; 50:9, s. 1006-1012
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Journal article (peer-reviewed)abstract
- OBJECTIVE:: What is the risk of impaired lung function in contemporary Swedish rubber workers and are there modifying effects of genetic variants? METHODS:: Included in the study were 159 rubber exposed and 118 not-rubber exposed workers. Lung function was analyzed as forced vital capacity percent of predicted and forced expiratory volume in 1 second percent of predicted. Levels of 2-thiothiazolidine-4-carboxylic acid (a marker of carbon disulfide and vulcanization fumes) was assessed with liquid chromatography tandem mass spectrometry. Polymorphisms in glutathione-related genes were analyzed by Taqman-based allelic discrimination and ordinary polymerase chain reaction. RESULTS:: There was an association between increasing levels of 2-thiothiazolidine-4-carboxylic acid and impaired lung function among exposed workers. The association was modified by glutathione S-transferase alpha 1 (GSTA1)-52 and GSTP1-114. GSTM1 had an influence on lung function among unexposed workers. CONCLUSIONS:: There may be a risk of impaired lung function in contemporary rubber workers. Gene-modifying effects may be considered in risk assessments.
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| 19. |
- Jönsson, Lena S, et al.
(author)
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N-nitrosamines in the southern Swedish rubber industries - exposure, health effects, and immunologic markers
- 2009
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In: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 35:3, s. 11-203
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim of this study was twofold: (i) to evaluate the air levels of N-nitrosamines in the Swedish rubber industry and (ii) to estimate the risk of symptoms and changed levels of immunologic markers in relation to these levels.METHODS: Using adsorption tubes, we collected samples of N-nitrosamines in the breathing zone of 96 rubber workers and analyzed them with liquid chromatography tandem mass spectrometry. Of these 96 workers, 66 were included in a medical examination and blood analysis together with an additional 106 rubber workers and 118 unexposed subjects. Medical and occupational histories were obtained in structured interviews, symptoms were recorded and immunologic markers analyzed in blood.RESULTS: The sum of N-nitrosamines ranged from less than the limit of detection to 36 microg/m (3)and differed with the vulcanization (ie, curing process) method used. Workers vulcanizing with a salt bath had the highest levels (median 4.2 microg/m (3)). Compared to the unexposed subjects, the rubber workers had an increased risk of nosebleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and changed levels of eosinophils and total immunoglobulin G (IgG). However, we found no clear exposure-response relationship with the symptoms or the immunologic markers studied.CONCLUSIONS: High levels of N-nitrosamines were found and must be lowered considerably in order to decrease the risk of cancer. There is a need for an occupational exposure limit for N-nitrosamines in Sweden. The lack of exposure-response relationships with the subacute symptoms examined in this study may be due to a healthy-worker selection or to the possibility that the symptoms are caused by an exposure not co-varying with N-nitrosamines.
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| 20. |
- Jönsson, Lena S, et al.
(author)
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Symptoms and immunologic markers among vulcanization workers in rubber industries in southern Sweden
- 2007
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In: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 33:4, s. 272-279
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Journal article (peer-reviewed)abstract
- Objectives The aim of this study was to estimate the risk of symptoms and the possible derangement of levels of immunologic markers for contemporary Swedish rubber workers. Furthermore, the relation between exposure and these biomarkers of response was examined using urinary levels of 2-thiothiazolidine-4-carboxylic acid (TTCA), which reflect the exposure. Methods Included in the study were 166 exposed workers and 117 controls. Medical and occupational histories were obtained in structured interviews. Symptoms were recorded, and immunologic markers were analyzed in blood. Urinary levels of TTCA were determined by liquid chromatography tandem mass spectrometry. Results Compared with the controls, the exposed workers had increased risks of eye symptoms [odds ratio (OR) 3.0], nose bleeds (OR 4.0), burning and dry throat (OR 3.0), hoarseness (OR 2.4), severe dry cough (OR 3.8), nausea (OR 4.3), and headache (OR 2.5). When the exposed workers were divided into three groups according to the TTCA levels, the highest risks were observed among the exposed workers with intermediate TTCA levels. Furthermore, the exposed workers in all of the TTCA subgroups had elevated concentrations of total immunoglobulin G when compared with the controls. Elevated concentrations of leukocytes, neutrophils, and eosinophils were observed in the group with high TTCA levels. Conclusions This work shows an increased risk of several symptoms and elevated levels of some immunologic markers among exposed workers in Swedish rubber industries. In addition, relationships between urinary levels of TTCA and some biomarkers of response were reported.
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| 21. |
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| 22. |
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| 23. |
- Staaf, Johan, et al.
(author)
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Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma
- 2013
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2020-2031
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Journal article (peer-reviewed)abstract
- Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss-of-heterozygosity (LOH), tumor ploidy and copy-neutral allelic imbalance in lung cancer, microarray-based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty-nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high-level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy-neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.
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| 24. |
- Stenvall, Anna, et al.
(author)
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Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3
- 2020
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
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Journal article (peer-reviewed)abstract
- Background: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. Results: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. Conclusion: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose–response relationships in animal organs and human tissue biopsies after internal exposure to radiation.
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| 25. |
- Sugihara, Yutaka, et al.
(author)
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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
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In: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
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Research review (peer-reviewed)abstract
- Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
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| 26. |
- Ullner, Magnus, et al.
(author)
-
A Monte Carlo study of titrating polyelectrolytes
- 1996
-
In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 104:8, s. 3048-3057
-
Journal article (peer-reviewed)abstract
- Monte Carlo simulations have been used to study three different models for linear, titrating polyelectrolytes in a salt-free environment: (i) a rigid polymer with rigid bonds (rigid rod); (ii) a flexible polymer with rigid bonds; and (iii) a flexible polymer with flexible bonds. The use of a very efficient pivot algorithm has made it possible to simulate very long chains, with up to several thousand titrating groups. The results have been compared to a mean field approximation for a rigid rod and variational results emanating from a Flory type approach. It is found that the rigid rod mean field model gives a qualitatively correct description for the apparent dissociation constant for all three models. At room temperature, the energy contribution to the apparent dissociation constant often dominates over the entropic term, which partly explains the relative success of this approach. In the case of flexible bonds, both the conformational behavior and the behavior of the apparent dissociation constant are well described by a variational ansatz with a quadratic term, largely thanks to the harmonicity of the bonds themselves. The approach is less successful for rigid bonds, which becomes evident for highly charged chains where a harmonic entropy term is incorrect. This can be remedied by replacing it with an expression valid in the strong coupling regime. Empirical scaling expressions have also been found, primarily for the end-to-end distance.
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| 27. |
- Ullner, Magnus, et al.
(author)
-
The electrostatic persistence length calculated from Monte Carlo, variational and perturbation methods
- 1997
-
In: Journal of Chemical Physics. - 0021-9606. ; 107:4, s. 1279-1287
-
Journal article (peer-reviewed)abstract
- Monte Carlo simulations and variational calculations using a Gaussian ansatz are applied to a model consisting of a flexible linear polyelectrolyte chain as well as to an intrinsically stiff chain with up to 1000 charged monomers. Addition of salt is treated implicitly through a screened Coulomb potential for the electrostatic interactions. For the flexible model the electrostatic persistence length shows roughly three regimes in its dependence on the Debye-Hückel screening length, κ-1. As long as the salt content is low and κ-1 is longer than the end-to-end distance, the electrostatic persistence length varies only slowly with κ-1. Decreasing the screening length, a controversial region is entered. We find that the electrostatic persistence length scales as √ξp/κ, in agreement with experiment on flexible polyelectrolytes, where ξp is a strength parameter measuring the electrostatic interactions within the polyelectrolyte. For screening lengths much shorter than the bond length, the κ-1 dependence becomes quadratic in the variational calculation. The simulations suffer from numerical problems in this regime, but seem to give a relationship half-way between linear and quadratic. A low temperature expansion only reproduces the first regime and a high temperature expansion, which treats the electrostatic interactions as a perturbation to a Gaussian chain, gives a quadratic dependence on the Debye length. For a sufficiently stiff chain, the persistence length varies quadratically with κ-1 in agreement with earlier theories.
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| 28. |
- Welinder, Charlotte, et al.
(author)
-
A protein deep sequencing evaluation of metastatic melanoma tissues.
- 2015
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Journal article (peer-reviewed)abstract
- Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
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| 29. |
- Welinder, Charlotte, et al.
(author)
-
Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
- 2014
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
-
Journal article (peer-reviewed)abstract
- Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
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| 30. |
- Welinder, Charlotte, et al.
(author)
-
Establishing a Southern Swedish Malignant Melanoma OMICS and Biobank Clinical Capability
- 2013
-
In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 2:1
-
Journal article (peer-reviewed)abstract
- Background: The Southern Swedish Malignant Melanoma (SSMM) research team is a truly cross functional group with members from oncology, clinical, surgery, bioinformatics, proteomics, and genomics initiatives. The SSMM’s objectives and goals are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. The science output in these resulting study outcomes further strengthens the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market. These patient biobank archives will be fully automated with novel ultralow temperature biobank storage units and used as a clinical resource. Methods: Clinical materials from patients before, during and after treatments, with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. We are developing standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community. Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that will be the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund will form the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are being associated with the biobank materials, including pathology reports on disease diagnosis on the MM patients. Conclusions: We provide data on the developments of protein profiling and targeted protein target assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden.
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| 31. |
- Welinder, Charlotte, et al.
(author)
-
Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.
- 2014
-
In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1315-1326
-
Journal article (peer-reviewed)abstract
- Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
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| 32. |
- Abolfathi, Bela, et al.
(author)
-
The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
-
In: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
-
Journal article (peer-reviewed)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 33. |
|
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| 34. |
- Albin, Maria, et al.
(author)
-
0253 Hairdressers are occupationally exposed to ortho- and meta- toluidine
- 2014
-
In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 71 Suppl 1, s. 32-33
-
Conference paper (peer-reviewed)abstract
- Hairdressing work is classified as carcinogenic based on excess risk for bladder cancer. We aimed at evaluating if current hairdressers are exposed to established/suspected bladder carcinogens (aromatic amines) and indicate possible sources of exposure.
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| 35. |
- Ali, Neserin, et al.
(author)
-
Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
- 2016
-
In: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
-
Journal article (peer-reviewed)abstract
- Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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| 36. |
- Almqvist, Monica, et al.
(author)
-
European Medical Imaging Technology Training, EMIT – ett prisbelönt EU-utbildningsprojekt
- 2005
-
In: [Host publication title missing].
-
Conference paper (peer-reviewed)abstract
- I ett sameuropeiskt Leonardo da Vinci-projekt har utvecklats ett internationellt utbildnings- och praktikpa- ket för blivande sjukhusfysiker [1-3]. Utbildningspaketet innehåller praktiska och kliniska övningsuppgifter där delta- garna tränas i för en sjukhusfysiker vanligt förekommande arbetsuppgifter. Målet har varit att det skall ge sjukhusfysi- kern den praktiska kompetens som krävs av det europeiska regelverket inom ämnesområdena magnetresonans (MRI), ultraljud, röntgendiagnostik, nuklearmedicin och strålbe- handling. Utbildningsmaterialet är webbaserat med en stor bilddata- bas och används redan i nära 70 länder runt om i världen. EMIT-projektet (European Medical Imaging Technology Training) belönades i december 2004 med det första Leonar- do da Vinci priset som delades ut till de tre bästa av totalt 4000 EU-projekt inom praktisk yrkesrelaterad utbildning. I projektet har vi konfronterats med den pedagogiska ut- maningen att förmedla praktisk kunskap, i sjukhusmiljöer med mycket olika förutsättningar beroende på vilket land deltagarna arbetar i. En omöjlig uppgift kan tyckas, men eftersom materialet är sammanställt av några av Europas starkaste forsknings- och utbildningsgrupper inom respekti- ve område så har det visat sig vara en stor tillgång och varje användare utnyttjar materialet efter sina egna behov. En an- nan erfarenhet är samarbetet över nationsgränser där vi har utnyttjat och konfronterats med likheter och oliktänkande inte minst vad gäller pedagogik och didaktik. Vi har dessut- om fått ett stort kontaktnät och många goda vänner. Den här presentationen beskriver delar av utbildningspaketet och erfarenheter av samarbetsprojektet.
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| 37. |
- Anand-Ivell, Ravinder, et al.
(author)
-
Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
- 2018
-
In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
-
Journal article (peer-reviewed)abstract
- The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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| 38. |
- André, Ingemar, et al.
(author)
-
Salt enhances calmodulin-target interaction
- 2006
-
In: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 90:8, s. 2903-2910
-
Journal article (peer-reviewed)abstract
- Calmodulin (CaM) operates as a Ca2+ sensor and is known to interact with and regulate hundreds of proteins involved in a great many aspects of cellular function. It is of considerable interest to understand the balance of forces in complex formation of CaM with its target proteins. Here we have studied the importance of electrostatic interactions in the complex between CaM and a peptide derived from smooth-muscle myosin light-chain kinase by experimental methods and Monte Carlo simulations of electrostatic interactions. We show by Monte Carlo simulations that, in agreement with experimental data, the binding affinity between CaM and highly charged peptides is surprisingly insensitive to changes in the net charge of both the protein and peptide. We observe an increase in the binding affinity between oppositely charged partners with increasing salt concentration from zero to 100 mM, showing that formation of globular CaM-kinase type complexes is facilitated at physiological ionic strength. We conclude that ionic interactions in complex formation are optimized at pH and saline similar to the cell environment, which probably overrules the electrostatic repulsion between the negatively charged Ca2+-binding domains of CaM. We propose a conceivable rationalization of CaM electrostatics associated with interdomain repulsion.
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| 39. |
- André, Ingemar, et al.
(author)
-
The role of electrostatic interactions in calmodulin-peptide complex formation
- 2004
-
In: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 87:3, s. 1929-1938
-
Journal article (peer-reviewed)abstract
- The complex between calmodulin and the calmodulin-binding portion of smMLCKp has been studied. Electrostatic interactions have been anticipated to be important in this system where a strongly negative protein binds a peptide with high positive charge. Electrostatic interactions were probed by varying the pH in the range from 4 to 11 and by charge deletions in CaM and smMLCKp. The change in net charge of CaM from similar to-5 at pH 4.5 to -15 at pH 7.5 leaves the binding constant virtually unchanged. The affinity was also unaffected by mutations in CaM and charge substitutions in the peptide. The insensitivity of the binding constant to pH may seem surprising, but it is a consequence of the high charge on both protein and peptide. At low pH it is further attenuated by a charge regulation mechanism. That is, the protein releases a number of protons when binding the positively charged peptide. We speculate that the role of electrostatic interactions is to discriminate against unbound proteins rather than to increase the affinity for any particular target protein.
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| 40. |
- Andreucci, Alessandro, et al.
(author)
-
Cadmium may impair prostate function as measured by Prostate Specific Antigen in semen: a cross-sectional study among European and Inuit men.
- 2015
-
In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 53:Feb 3, s. 33-38
-
Journal article (peer-reviewed)abstract
- We investigated the association between cadmium in blood and the concentration of the prostate specific antigen (PSA) in semen, including the modifying effects of zinc or the CAG polymorphism in the androgen receptor (AR). Blood and semen samples were collected from 504 partners of pregnant women in Greenland, Poland and Ukraine. We found an inverse trend between cadmium and PSA (log (ß)= -0.121, 95% Confidence Interval (CI):-0.213; -0.029, P=0.0103) in Greenlandic men. Similar results were observed in men with a high number of CAG repeats (CAG 24) (log (ß)=-0.231, 95% CI:-0.363; -0.098, P=0.0009). Inverse trends between cadmium and PSA were found when semen zinc concentrations were below the median value for men from Ukraine and Greenland. These outcomes suggest that cadmium may impair prostate function, as measured by PSA in semen, while high zinc levels and a low number of CAG repeats protects against this action.
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| 41. |
- Annertz, Mårten, et al.
(author)
-
No relationship between epidural fibrosis and sciatica in the lumbar postdiscectomy syndrome. A study with contrast-enhanced magnetic resonance imaging in symptomatic and asymptomatic patients
- 1995
-
In: Spine. - 0362-2436. ; 20:4, s. 449-453
-
Journal article (peer-reviewed)abstract
- STUDY DESIGN. Symptomatic patients were retrospectively analyzed and compared with a control group from an ongoing prospective and consecutive study. OBJECTIVES. To determine the presence and extent of epidural fibrosis in patients with and without recurrent sciatic pain after previous lumbar discectomy, contrast-enhanced magnetic resonance images were evaluated and correlated with surgical findings in the symptomatic patients. Recurrent hernia and bony stenosis were ruled out as the probable causative agent, as well as any morphologic explanation other than fibrosis. SUMMARY OF BACKGROUND DATA. Repeat surgical results for patients with the lumbar postdiscectomy syndrome with epidural fibrosis alone are often unfavorable. The pathogenic role of epidural fibrosis, however, has not been established. METHODS. The magnetic resonance images of eight patients with recurrent or persistent sciatic pain after lumbar discectomy were compared with those of eight asymptomatic patients constituting a control group. All were examined with magnetic resonance imaging on a 0.3 T unit before and after intravenous injection of gadolinium-DTPA, and clinically, 6 months to 4 years after surgery. The symptomatic patients subsequently underwent reoperation. RESULTS. Fourteen patients had focal or diffuse epidural fibrosis around the nerve root and/or the thecal sac at the operated level, whereas the postoperative findings for two patients were "normal," one in the operated and one in the control group. No difference between the groups regarding mass effect or affection of the nerve roots or thecal sac was noted. At reoperation of the eight symptomatic patients, fibrosis was the only pathologic finding in all cases except one, in which surgery confirmed the normal finding on magnetic resonance imaging. Six of the eight operated patients had recurrent or persistent symptoms within a year of the reoperation. CONCLUSION. No differences regarding the presence and extent of epidural fibrosis between the symptomatic and asymptomatic patients could be demonstrated with contrast-enhanced magnetic resonance imaging. The role of epidural fibrosis as the causative agent in the lumbar postdiscectomy syndrome is questioned.
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| 42. |
- Annertz, Mårten, et al.
(author)
-
Serial MRI in the early postoperative period after lumbar discectomy
- 1995
-
In: Neuroradiology. - 1432-1920. ; 37:3, s. 177-182
-
Journal article (peer-reviewed)abstract
- The aim of this study was to determine MRI findings in patients successfully operated upon for lumbar disc herniation. We investigated 20 patients with a successful outcome after L4-5 or L5-S1 disc operations clinically and with MRI preoperatively, and at 5 days, 6 weeks, and 4 months after surgery. Postoperatively, T1- and T2-weighted images were obtained. At 4 months gadolinium-enhanced images were added. Pronounced intraspinal MRI changes were seen during follow-up. Deformation of the dural sac was seen in 13 patients preoperatively, in 19 at 5 days after operation, in 15 at 6 weeks, and in 12 at 4 months. Nerve root involvement was seen in all cases both preoperatively and at 5 days after operation, in 17 at 6 weeks, and in 15 at 4 months. No correlation between symptoms or the straight leg raising test and the size or nature of the abnormal tissue in the spinal canal postoperatively could be demonstrated. It was concluded that early postoperative MRI after lumbar discectomy must be interpreted carefully, and that oedema and scar formation are probable reasons for difficulties in interpretation.
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| 43. |
- Anundi, Helena, et al.
(author)
-
Air and biological monitoring of solvent exposure during grafitti removal
- 2000
-
In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 73:8, s. 561-569
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures.METHODS: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews.RESULTS: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high.CONCLUSIONS: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.
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| 44. |
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| 45. |
- Attié, David, et al.
(author)
-
A time projection chamber with GEM-based readout
- 2017
-
In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 856, s. 109-118
-
Journal article (peer-reviewed)abstract
- For the International Large Detector concept at the planned International Linear Collider, the use of time projection chambers (TPC) with micro-pattern gas detector readout as the main tracking detector is investigated. In this paper, results from a prototype TPC, placed in a 1. T solenoidal field and read out with three independent Gas Electron Multiplier (GEM) based readout modules, are reported. The TPC was exposed to a 6. GeV electron beam at the DESY II synchrotron. The efficiency for reconstructing hits, the measurement of the drift velocity, the space point resolution and the control of field inhomogeneities are presented.
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| 46. |
- Axelsson, Jonatan, et al.
(author)
-
Phthalate exposure and reproductive parameters in young men from the general Swedish population.
- 2015
-
In: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 85, s. 54-60
-
Journal article (peer-reviewed)abstract
- In animals, exposure to certain phthalates negatively affects the male reproductive function. Human results are conflicting and mostly based on subfertile males, in whom the association between exposure and reproductive function may differ from the general population.
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| 47. |
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| 48. |
|
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| 49. |
- Axmon, Anna, et al.
(author)
-
Rapid decline of persistent organochlorine pollutants in serum among young Swedish males
- 2008
-
In: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 70:9, s. 1620-1628
-
Journal article (peer-reviewed)abstract
- To investigate a possible time trend in serum concentrations of persistent organochlorine pollutants (POPs), representative samples of the young (median age 18 years) Swedish male population were investigated in the years 2000 and 2004. Due to their low age, these men were assumed not to have reached steady state of body burdens of POPs, why their serum concentrations were considered to represent ongoing dietary exposure. Serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethylene (p,p'-DDE), two biomarkers of exposure to POPs, were available for 274 and 223 men, respectively, in 2000 and for 200 men in 2004. The percentage of men with CB-153 or p,p'-DDE below the limit of detection (LOD) was significantly higher in 2004 than in 2000 (30% vs. none, p < 0.001 for CB-153 and 65% vs. 6%, p < 0.001 for p,p'-DDE). Moreover, the median serum concentration of CB-153 decreased from 66ngg(-1) lipid to 19ngg(-1), corresponding to a yearly decrease of about 26%. The analogous analysis was not done for p,p'-DDE since the median serum concentration in 2004 was below the LOD.
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| 50. |
- Axmon, Anna, et al.
(author)
-
Tidstrender för perfluorerade ämnen i plasma från svenska kvinnor 1987-2007
- 2014
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Reports (other academic/artistic)abstract
- Perfluorerade kemikalier (PFC) är en stor grupp ämnen som är misstänkt hormon- störande. De är svårnedbrytbara och stannar länge i både miljö och människa. De mest kända PFC är PFOS och PFOA. Dessa användes under många år för att im- pregnera textilier, skor, möbler och mattor, i golv- och bilvax och målarfärger, mm. Användningen började minska i början av detta århundrade då PFOS och PFOA ersattes av andra PFC. Vi använde sparade plasmaprover från 80 kvinnor. Proven togs ursprungligen mellan 1987 och 2007 i samband med bröstförminskningsoperationer, från kvinnor som vi- sade sig friska vid screening för ärftlig cancer och från kvinnor vars äkta män hade cancer. Proverna analyserades för ett antal olika PFC (se textruta nedan), och vi undersökte därefter tidstrender för varje kemikalie. Vi tittade dels på linjära tidstrender, dvs vi an- tog att förändringen i halter var lika stor för varje år, och dels på förändringar mellan perioderna före 1990, 1990-2000 och efter 2000. • PFNA och PFDA ökade över hela tidsperioden, men allra mest efter 2000. Från 1987 till 2007 ökade PFNA med 305% och PFDA med 312%. • PFUnDA ökade med 155% från 1987 till 2007. Detta berodde framför allt på en stor ökning från 2000 och framåt. • PFOS och PFOA låg som högst under perioden 1990-2000. Sett över hela studieperioden, dvs 1987 till 2007, minskade PFOS med 36% och PFOA med 7%. • Även PFHxS låg som högst under perioden 1990-2000. Till skillnad från PFOS och PFOA uppvisade PFHxS en ökning – 142% – mellan 1987 och 2007.
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