| 1. |
- Ageberg, Malin, et al.
(författare)
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Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines.
- 2011
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 317, s. 1179-1191
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Tidskriftsartikel (refereegranskat)abstract
- Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line- based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitises DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor, FTI-277, or the geranylgeranyl transferase I inhibitor, GGTI-298, indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.
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| 2. |
- Bryland, Anna, et al.
(författare)
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Infusion fluids contain harmful glucose degradation products.
- 2010
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; May 4, s. 1213-1220
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients.
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| 3. |
- Dencker, Magnus, et al.
(författare)
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Aerobic fitness related to cardiovascular risk factors in young children.
- 2012
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Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 171:4, s. 705-710
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Tidskriftsartikel (refereegranskat)abstract
- Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual - mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO(2PEAK) and composite risk factor score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO(2PEAK) (P < 0.001); thus, higher VO(2PEAK) was associated with lower composite risk factor score for CVD. In conclusion, low VO(2PEAK) is associated with an elevated composite risk factor score for CVD in both young boys and girls.
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| 4. |
- Dencker, Magnus, et al.
(författare)
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Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children.
- 2012
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Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 20, s. 1104-1108
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Tidskriftsartikel (refereegranskat)abstract
- In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.
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| 5. |
- Dencker, Magnus, et al.
(författare)
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Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in pre-pubertal children.
- 2012
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:8
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Tidskriftsartikel (refereegranskat)abstract
- Aim We analysed whether total body fat, abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods Cross-sectional study of 238 children aged 8-11 years. Total body fat (TBF) and abdominal fat mass (AFM) were measured by DXA. TBF was expressed as a percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO(2PEAK) ), systolic and diastolic blood pressure (SBP, DBP), and resting heart rate (RHR) were measured. Mean artery pressure (MAP) and pulse pressure (PP) were calculated. Left atrial diameter (LA) was measured, and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z-scores were calculated. Sum of z-scores for SBP, DBP, MAP, PP, RHR, LVM, LA, RWT, and -VO(2PEAK) were calculated in boys and girls, separately, and used as composite risk factor score. Results Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r=0.56, r=0.59, and r=0.48, all P<0.001, and for girls r=0.45, r=0.50, and r=0.48, all P<0.001. Conclusion Total body fat, abdominal fat and body fat distribution were all associated with higher composite risk factor scores for CVD in young children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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| 6. |
- Dencker, Magnus, et al.
(författare)
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Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children.
- 2011
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Ingår i: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7174 .- 1747-7166. ; 6:2-2, s. 597-602
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population-based level. Methods. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute values of VO(2PEAK) (0.22-0.36, P< 0.05), and for VO(2PEAK) scaled by body mass (-0.38 - -0.70, P<0.05). No relationships were detected for VO(2PEAK) scaled to LBM (-0.17-0.04, all not significant). Boys and girls in the lowest quartile according to body fat measurements had higher absolute values of VO(2PEAK) and lower values of VO(2PEAK) scaled by body mass, compared with those in the highest quartile. No differences were found for VO(2PEAK) scaled to LBM. Conclusions. Our findings document the coexistence of two known risk factors for disease at a young age and confirms that VO(2PEAK) was scaled to LBM may be a better, body fat independent way of expressing fitness.
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| 7. |
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| 8. |
- Hindorf, Cecilia, et al.
(författare)
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EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry
- 2010
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 37:6, s. 1238-1250
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Tidskriftsartikel (refereegranskat)abstract
- The level of administered activity in radionuclide therapy is often limited by haematological toxicity resulting from the absorbed dose delivered to the bone marrow. The purpose of these EANM guidelines is to provide advice to scientists and clinicians on data acquisition and data analysis related to bone-marrow and whole-body dosimetry. The guidelines are divided into sections "Data acquisition" and "Data analysis". The Data acquisition section provides advice on the measurements required for accurate dosimetry including blood samples, quantitative imaging and/or whole-body measurements with a single probe. Issues specific to given radiopharmaceuticals are considered. The Data analysis section provides advice on the calculation of absorbed doses to the whole body and the bone marrow. The total absorbed dose to the bone marrow consists of contributions from activity in the bone marrow itself (self-absorbed dose) and the cross-absorbed dose to the bone marrow from activity in bone, larger organs and the remainder of the body. As radionuclide therapy enters an era where patient-specific dosimetry is used to guide treatments, accurate bone-marrow and whole-body dosimetry will become an essential element of treatment planning. We hope that these guidelines will provide a basis for the optimization and standardization of the treatment of cancer with radiopharmaceuticals, which will facilitate single- and multi-centre radionuclide therapy studies.
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