| 1. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Andersson, Hans, et al.
(författare)
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Complete regioselective addition of grignard reagents to pyrazine N-oxides, toward an efficient enantioselective synthesis of substituted piperazines.
- 2010
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Ingår i: Organic letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 12:2, s. 284-6
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Tidskriftsartikel (refereegranskat)abstract
- A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.
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| 3. |
- Ekman, Bertil, et al.
(författare)
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A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
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| 4. |
- Elander, Nils, 1980-, et al.
(författare)
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Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APCMin/+ mice
- 2008
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 372:1, s. 249-253
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Tidskriftsartikel (refereegranskat)abstract
- The induced synthesis of bioactive prostanoids downstream of cyclooxygenase-2 (COX-2) and prostaglandin H2 (PGH2) exerts a critical event in colorectal carcinogenesis. Here we demonstrate that APCMin/+ mice with genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), which catalyses the terminal conversion of PGH2 into PGE2, surprisingly develop more and generally larger intestinal tumors than do mPGES-1 wild type littermates (mean number of tumors/intestine 80 vs. 38, p < 0.0005, mean tumor diameter 1.64 vs. 1.12 mm, p < 0.0005). No deviation regarding the expression of other PGE2 related enzymes (COX-1, COX-2, mPGES-2, cPGES, and 15-PGDH) or receptors (EP1-4) was obvious among the mPGES-1 deficient mice. PGE2 levels were suppressed in tumors of mPGES-1 deficient animals, but the concentrations of other PGH2 derived prostanoids were generally enhanced, being most prominent for TxA2 and PGD2. Thus, we hypothesise that a redirected synthesis towards other lipid mediators might (over)compensate for loss of mPGES-1/PGE2 during intestinal tumorigenesis. Nevertheless, our results question the suitability for mPGES-1 targeting therapy in the treatment or prevention of colorectal cancer. © 2008 Elsevier Inc. All rights reserved.
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| 5. |
- Engel, C., et al.
(författare)
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Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2859-2868
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers.Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers.Impact: The combined application of these and other recently identified genetic riskmodifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.
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| 6. |
- Erlandsson, Ragnar, et al.
(författare)
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Scanning force microscopy - examples of applications to surface chemistry
- 1992
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Ingår i: Progress in Colloid and Polymer Science. - 0340-255X .- 1437-8027. ; 88, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- Some recent results from the scanning force microscopy activity at our laboratory are presented. A brief description of attractive mode force microscopy is followed by a discussion of the following examples: O2/H2-induced morphology changes in thin palladium films, structure of spin cast polysulfone films, fibrinogen adsorption on hydrophobic SiO2, and force measurements on hydrophobic/hydrophilic substrates.
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| 7. |
- Fridell, Erik, 1963, et al.
(författare)
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Model studies of NOx storage and sulphur deactivation of NOx storage catalysts
- 2001
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Ingår i: Topics in Catalysis. - 1572-9028 .- 1022-5528. ; 16-17:1-4, s. 133-137
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Tidskriftsartikel (refereegranskat)abstract
- The storage of NOx under lean conditions in model NOx storage catalysts as well as the deactivation by sulphur have been studied. We find that NO2 plays an important role in the storage mechanism as an oxidising agent. Two different mechanisms for this are discussed: the formation of surface peroxides and the oxidation of nitrites to nitrates, FTIR studies show that NOx is stored as surface nitrates, The sulphur deactivation is found to be more severe when SO2 is added during the rich phase than when SO2 is added during the lean period. FTIR shows the formation of bulk sulphates both under lean and rich conditions.
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| 8. |
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| 9. |
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| 10. |
- Fridell, Erik, 1963, et al.
(författare)
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The Mechanism for NOx Storage
- 2000
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Ingår i: Catalysis Letters. - 1572-879X .- 1011-372X. ; 66:1-2, s. 71-74
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms for storing of NOx in platinum-barium-alumina catalysts during lean-rich transients are investigated. Oxidation of NO to NO2 is found to be an important step. NO2 is found to be important for oxidation of the catalyst or of nitrites to form nitrates. NOx is then stored in the form of surface nitrates. FTIR studies show no formation of bulk nitrates in these experiments.
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