| 1. |
- Fedorov, R V, et al.
(författare)
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Structure of ribosomal protein TL5 complexed with RNA provides new insights into the CTC family of stress proteins
- 2001
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; D57:7, s. 968-976
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of Thermus thermophilus ribosomal protein TL5 in complex with a fragment of Escherichia coli 5S rRNA has been determined at 2.3 Å resolution. The protein consists of two domains. The structure of the N-terminal domain is close to the structure of E. coli ribosomal protein L25, but the C-terminal domain represents a new fold composed of seven -strands connected by long loops. TL5 binds to the RNA through its N-terminal domain, whereas the C-terminal domain is not included in this interaction. Cd2+ ions, the presence of which improved the crystal quality significantly, bind only to the protein component of the complex and stabilize the protein molecule itself and the interactions between the two molecules in the asymmetric unit of the crystal. The TL5 sequence reveals homology to the so-called general stress protein CTC. The hydrophobic cores which stabilize both TL5 domains are highly conserved in CTC proteins. Thus, all CTC proteins may fold with a topology close to that of TL5.
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| 2. |
- Smits, KM, et al.
(författare)
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Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
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| 3. |
- Berthelot, V, et al.
(författare)
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Hepatic metabolism of propionate and methylmalonate in growing lambs
- 2002
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Ingår i: Livestock Production Science. - 0301-6226. ; 74:1, s. 33-43
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Tidskriftsartikel (refereegranskat)abstract
- The hepatic extraction ratio or propionate and the net hepatic flux of methylmalonate (MMA) were investigated in six Suffolk lambs (32.7 +/- 1.7 kg BW) implanted with catheters in a mesenteric artery and in the portal, hepatic, and ruminal veins and a cannula in the rumen. The lambs were fed a pelleted barley-based diet (1.1 kg DM per day) and subjected to three intravenous infusion protocols separated by at least 7 days: saline (C; control), butyrate (B; 0.2 mmol/h/kg BW) or lactate (L; 0.96 mmol/h/kg BW). The solutions were infused continuously into the ruminal vein for 13 h. At the same time as the intravenous infusion treatments, propionate (1.78 mmol/h/kg BW) was infused intraruminally for 4 h starting 4 h after the initiation of the experimental protocol. Arterial, portal and hepatic blood samples were obtained during the last 10 h of the infusion protocol. Blood flow was measured by down stream dilution of p-aminohippuric acid. The hepatic extraction ratio of propionate decreased from 85 +/- 3 to 75 +/- 1% after intraruminal infusion of propionate and the net splanchnic appearance of propionate increased threefold with the doubling of the net portal appearance of propionate. Intravenous infusion of lactate or butyrate did not affect the hepatic extraction ratio or net splanchnic flux of propionate. The net portal appearance, net hepatic flux and net splanchnic appearance of MMA were not (P > 0.10) different from zero in all situations. The arterial concentration of MMA increased with increasing absorption rate of propionate but remained below 2 mumol/l throughout the experiment. The results of the present study do not support the hypothesis that the MMA possibly incorporated into methyl-branched chain fatty acids in adipose tissue of intensively-reared lambs is of hepatic origin.
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| 4. |
- Kristensen, Brian K., et al.
(författare)
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Identification of oxidised proteins in the matrix of rice leaf mitochondria by immunoprecipitation and two-dimensional liquid chromatography-tandem mass spectrometry
- 2004
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 65:12, s. 1839-1851
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Tidskriftsartikel (refereegranskat)abstract
- Highly purified mitochondria were isolated from green 7-day-old rice leaves. The mitochondria were sonicated and the matrix fraction isolated as the 100,000g supernatant. Part of the matrix fraction was left untreated while the other part was subjected to a mild oxidative treatment (0.5 mM H2O2 + 0.2 mM CuSO4 for 10 min at room temperature). The oxidised proteins in both samples were tagged with dinitrophenylhydrazine (DNP), which forms a covalent bond with carbonyl groups. The DNP-tagged proteins were immunoprecipitated using anti-DNP antibodies and digested with trypsin. The mixture of peptides was analysed by nano-HPLC coupled online to an ESI-Quad-TOF mass spectrometer. The peptides were separated by stepwise ion exchange chromatography followed by reverse phase chromatography (2D-LC), and analysed by MS/MS. Proteins were identified by un-interpreted fragment ion database searches. Using this approach we identified 20 oxidised proteins in the control sample and a further 32 in the oxidised sample. Western blots of 2D-gels of the same samples prior to immunoprecipitation verified that the oxidation treatment increases protein oxidation also for specific proteins. Likewise Western blots showed that neither the isolation of mitochondria nor their subfractionation introduced carbonyl groups. We therefore conclude that a number of proteins are oxidised in the matrix of rice leaf mitochondria in vivo and further identify a group of proteins that are particularly susceptible to mild oxidation in vitro.
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| 5. |
- Kristensen, T N, et al.
(författare)
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The increase of fluctuating asymmetry in a monoclonal strain of collembolans after chemical exposure - discussing a new method for estimating the environmental variance
- 2004
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Ingår i: Ecological Indicators. - : Elsevier BV. - 1872-7034 .- 1470-160X. ; 4:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The increasing demand for detecting and quantifying the negative effects on natural habitats caused by anthropogenic activity has led to the development of impact assessment tools. Here, we propose a monitoring method based on the concept of developmental instability (DI) estimated from fluctuating asymmetry (FA) in bilateral morphological traits in a monoclonal strain. The use of monoclonal populations conveys certain advantages over sexual populations when interpreting fluctuating asymmetry results. This is because the inherent problems of genetic heterogeneity are circumvented. Our investigation demonstrates in practice, how an estimate of the environmental component of the phenotypic variance in a population can be achieved. This estimate can be used to eliminate samples where the presence of macro environmental variance has influenced the estimated level of fluctuating asymmetry significantly. Avoiding the confounding effect due to the presence of genetic variance and controlling the environmental variance component enable a more accurate estimate of the possible detrimental effects of the putative stressing agents. We used a clonal strain of the springtail Folsomia candida exposed to three different contaminants; tributyltin, nonylphenol and bis(2-ethylhexyl)-phthalate (DEPH), in order to test the general applicability of the proposed method. The results show that the method is efficient in discriminating between environments exposed to chemical stress and control environments. However, establishing an actual dose-response relationship was only possible for one of the contaminants, nonylphenol.
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| 6. |
- Smits, KM, et al.
(författare)
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Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study
- 2003
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Ingår i: Biomarkers. - : Informa UK Limited. - 1366-5804 .- 1354-750X. ; 8:3-4, s. 299-310
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi(2) = 0.007, p = 0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype.
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| 7. |
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| 8. |
- Tropé, C, et al.
(författare)
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Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument
- 2000
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 0923-7534. ; 11:3, s. 8-281
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor.PATIENTS AND METHODS: Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points.RESULTS: Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001.CONCLUSIONS: Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.
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