| 1. |
- Yang, Y, et al.
(författare)
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Ring opening of benzo[a]pyrene in the germ-free rat is a novel pathway for formation of potentially genotoxic metabolites
- 2000
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 39:50, s. 15585-15591
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Tidskriftsartikel (refereegranskat)abstract
- The metabolism of benzo[a]pyrene (BP) is known to lead to a large number of oxygenated compounds, some of which can bind covalently to DNA. We have studied the integrated metabolism of BP in vivo in germ-free rats given C-14-labeled BP. Urinary metabolites were separated into groups according to acidity using lipophilic ion exchangers. The groups were analyzed by mass spectrometry and were further fractionated by high-performance liquid chromatography. The fraction of urinary metabolites previously shown to contain N-acetylcysteine and glucuronic acid conjugates was found to contain derivatives of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid as major components. These compounds, which were identified by mass spectrometry and NMR, accounted for about 30% of the total metabolites in urine, demonstrating that, surprisingly, ring opening is a major pathway for metabolism of BP in the germ-free rat. The dicarboxylic acid may be excreted in urine as an ester glucuronide. By using the single cell gel electrophoresis or COMET assay, we were able to demonstrate that the anhydride of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid was an efficient inducer of DNA damage. Taken together, these results indicate that the novel ring opening metabolic pathway may provide alternative mechanisms for the toxicity of BP.
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| 2. |
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| 3. |
- Thiel, V, et al.
(författare)
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Analysis of archaeal core ether lipids using Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS): Exploring a new prospect for the study of biomarkers in geobiology
- 2007
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Ingår i: Geobiology. - 1472-4677 .- 1472-4669. ; 5:1, s. 75-83
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Tidskriftsartikel (refereegranskat)abstract
- The capability of Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) of analysing molecular archaeal biomarkers in geobiological samples was tested and demonstrated. Using a bismuth cluster primary ion source, isopranyl glycerol di- and tetraether core lipids were detected in small amounts of total organic extracts from methanotrophic microbial mats, simultaneously and without further chemical treatment and chromatographic separation. ToF-SIMS was also employed to track the distribution of fossilized ether lipids in a massive carbonate (aragonite) microbialite that precipitated as a result of the microbial anaerobic oxidation of methane. An unambiguous signal was obtained when analysing a freshly broken rock surface (base of a microdrill core). Though some limitation occurred due to μm-topographical effects (sample roughness), it was possible to display the abundance of high molecular weight (C86) of tetraethers exposed in particular regions of the rock surface. 'Molecular mapping' revealed that a part of these molecules was encased within the rock fabric in a cluster-like distribution that might trace the arrangement of the calcifying microbial colonies in the once active mat system. The results reveal promising perspectives of ToF-SIMS for (i) the quasi-nondestructive analysis of lipids in extremely small geobiological samples at low concentrations; (ii) resolving the spatial distribution of these compounds on a μm2- to cm2-scale; and (iii) the more exact assignment of lipid biomarkers to their biological source. © 2006 The Authors.
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| 4. |
- Bajor, Antal, 1962, et al.
(författare)
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Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption.
- 2009
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Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 197:2, s. 129-37
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Tidskriftsartikel (refereegranskat)abstract
- The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the (75)SeHCAT test.
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| 5. |
- Fredriksson, I, et al.
(författare)
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Consequences of axillary recurrence after conservative breast surgery
- 2002
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 89:7, s. 902-908
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to study the incidence, time course and prognosis of patients who developed axillary recurrence after breast-conserving surgery, and to evaluate possible risk factors for axillary recurrence and prognostic factors after axillary recurrence. Methods: In a population-based cohort of 6613 women with invasive breast cancer who had breast-conserving surgery between 1981 and 1990, 92 recurrences in the ipsilateral axilla were identified. Risk factors for axillary recurrence were studied in a case-control study nested in the cohort, and late survival was documented in the women with axillary recurrence. Results: The overall risk of axillary recurrence was 1.0 per cent at 5 years and 1.7 per cent at 10 years. The risk of axillary recurrence increased with tumour size (P = 0.033) and was highest in younger women (odds ratio (OR) 3.9 for women aged less than 40 years compared with those aged 50-59 years). Radiotherapy to the breast reduced the risk of axillary recurrence (OR 0.1 (95 per cent confidence interval 0.1 to 0.4)). The breast cancer-specific survival rate after axillary recurrence, as measured from primary treatment, was 78.0 per cent at 5 years and 52.3 per cent at 10 years. Tumour size and node status had a statistically significant effect on death from breast cancer. Conclusion: Axillary recurrence is rare, although more common in younger women with large tumours. Radiotherapy to the breast was protective. Tumour size and node status were the most important prognostic factors in women with axillary recurrence.
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| 6. |
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| 7. |
- Fredriksson, I, et al.
(författare)
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Local recurrence in the breast after conservative surgery - A study of prognosis and prognostic factors in 391 women
- 2002
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 38:14, s. 1860-1870
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based cohort of 6613 women with invasive breast cancer, who had breast-conserving surgery between 1981 and 1990, 391 recurrences in the operated breast were identified. The main aim of this study was to examine the prognosis and prognostic factors in different subgroups of local recurrences, characterised by the time to recurrence, location of recurrence and previously given radiotherapy. The median follow-up for women who had a local recurrence was 7.9 years. The life-table estimates for breast cancer-specific survival in women with local recurrences were 84.5% (standard error (S.E.) 1.8) at 5 years and 70.9% (S.E. 2.7) at 10 years. The risk of breast cancer death was highest among women who had an early (=2 years) recurrence in the same quadrant as the primary tumour, with a breast cancer-specific survival of 67.9% (S.E. 4.8) at 5 years and 56.0% (S.E. 5.9) at 10 years. There was a statistically significant difference in the probability of breast cancer-specific survival, as measured from the recurrence, between women who initially did or did not receive radiotherapy (P=0.0123). However, when measured from primary treatment, there was no significant difference, indicating that the difference in prognosis could be due to a lead-time bias. Independent prognostic factors for breast cancer-specific survival in women with local recurrences were time to local recurrence and the Nottingham Prognostic Index (NPI). ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 8. |
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| 9. |
- Fredriksson, I, et al.
(författare)
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Risk factors for local recurrence after breast-conserving surgery
- 2003
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:9, s. 1093-1102
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. Method: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. Results: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. Conclusion: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.
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