| 1. |
- Brinkmalm, Gunnar, et al.
(författare)
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An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
- 2012
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1096-9888 .- 1076-5174. ; 47:5, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
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| 2. |
- El-Serafi, Ahmed, 1977-, et al.
(författare)
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Vitamin D levels and busulphan kinetics in patients undergoing hematopoietic stem cell transplantation, a multicenter study
- 2021
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Ingår i: Bone Marrow Transplantation. - : SPRINGERNATURE. - 0268-3369 .- 1476-5365. ; 56, s. 807-817
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P < 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.
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| 3. |
- Malmström, Per, et al.
(författare)
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Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.
- 2003
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Ingår i: European journal of cancer (Oxford, England : 1990). - 0959-8049. ; 39, s. 1690-
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Tidskriftsartikel (refereegranskat)abstract
- The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.
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| 4. |
- Mattsson, Jonas, 1966, et al.
(författare)
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Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation.
- 2001
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Ingår i: British journal of haematology. - : Wiley. - 0007-1048. ; 115:4, s. 935-44
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Tidskriftsartikel (refereegranskat)abstract
- We report the clinical outcome and results of chimaerism analysis in various cell lineages of 30 patients given non-myeloablative conditioning, followed by allogeneic stem cell transplantation (SCT). The commonest diagnoses were chronic myelogenous leukaemia (n = 11) and solid tumours (n = 11). Twenty-one patients received SCT from human leucocyte antigen (HLA)-identical siblings and nine from matched unrelated donors. Median patient age was 53 (28-77) years. Four non-myeloablative protocols were used, including fludarabine (30 mg/m2 x 3-6), busulphan (4 mg/kg x 2), cyclophosphamide (Cy) (30 mg/kg/day x 2) or total body irradiation (2 Gy), and anti-thymocyte globulin. The patients were analysed by polymerase chain reaction (PCR) analysis of minisatellites on days 14, 21 and 28, then every other week up to 3 months and monthly thereafter. All samples were cell separated for T, B and myeloid cells using immunomagnetic beads. Eighteen patients were alive at a median follow-up of 11 (6-20) months. Acute graft-versus-host disease (GVHD) occurred in 22 patients. Eighteen of the 22 patients with acute GVHD showed mixed chimaerism (MC) in the T-cell fraction at the time of acute GVHD. However, all patients with acute GVHD showed donor chimaerism (DC) in the T-cell fraction median 76 (7-414) days after onset versus three out of eight patients without acute GVHD, P < 0.001]. Disease response was diagnosed in 15 patients, median 100 (37-531) days after SCT. At the time of disease response, six out of 15 patients showed MC in the T-cell fraction. In conclusion, mixed chimaerism in the T-cell fraction is common at the time of acute GVHD and disease response in patients conditioned with non-myeloablative therapy.
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| 5. |
- Mattsson, Lisa, et al.
(författare)
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Waste of fresh fruit and vegetables at retailers in Sweden : Measuring and calculation of mass, economic cost and climate impact
- 2018
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Ingår i: Resources, Conservation and Recycling. - : Elsevier BV. - 0921-3449 .- 1879-0658. ; 130, s. 118-126
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Tidskriftsartikel (refereegranskat)abstract
- Food waste is a significant problem for environmental, economic and food security reasons. The retailer, food service and consumers have been recognised as the parts of the food supply chain where the possibility of reducing food waste is greatest in industrialised countries. In this study, primary data on fresh fruit and vegetables (FFV) waste collected through direct measurements in three large retail stores in Sweden were analysed from the perspectives of wasted mass, economic cost and climate impact. A method of measuring and calculating the economic cost of FFV waste was developed and includes the cost of wasted produce, the cost of personnel time for waste management and the cost of waste collection and disposal. The results show that seven FFV categories, which have been termed "hotspot categories", contributed to the majority of the waste, both in terms of wasted mass, economic cost and climate impact. The "hotspot categories" are apple, banana, grape, lettuce, pear, sweet pepper, and tomato. The cost benefit analysis conducted showed that it is economically wise to invest in more working time for employees in waste management to accomplish a reduction of wasted mass and climate impact without an economic loss for the store. These results are relevant for supporting the implementation of policies and initiatives aimed at food waste reduction at retail level.
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