| 1. |
- Minet, Ariane D., et al.
(author)
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Teneurin-1, a vertebrate homologue of the Drosophila pair-rule gene ten-m, is a neuronal protein with a novel type of heparin-binding domain
- 1999
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In: Journal of Cell Science. - 0021-9533. ; 112:12, s. 2019-2032
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Journal article (peer-reviewed)abstract
- The Drosophila gene ten-m is the first pair-rule gene not encoding a transcription factor, but an extracellular protein. We have characterized a highly conserved chicken homologue that we call teneurin-1. The C-terminal part harbors 26 repetitive sequence motifs termed YD-repeats. The YD-repeats are most similar to the core of the rhs elements of Escherichia coli. Related repeats in toxin A of Clostridium difficile are known to bind specific carbohydrates. We show that recombinantly expressed proteins containing the YD-repeats of teneurin-1 bind to heparin. Furthermore, heparin lyase treatment of extracts of cells expressing recombinant YD-repeat protein releases this protein from high molecular mass aggregates. In situ hybridization and immunostaining reveals teneurin-1 expression in neurons of the developing visual system of chicken and Drosophila. This phylogenetic conservation of neuronal expression from flies to birds implies fundamental roles for teneurin-1 in neurogenesis. This is supported by the neurite outgrowth occurring on substrates made of recombinant YD-repeat proteins, which can be inhibited by heparin. Database searches resulted in the identification of ESTs encoding at least three further members of the teneurin family of proteins. Furthermore, the human teneurin-1 gene could be identified on chromosome Xq24/25, a region implied in an X-linked mental retardation syndrome.
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| 2. |
- Travis, L. B., et al.
(author)
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Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin´s lymphoma
- 1995
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 87:7, s. 524-530
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Review (other academic/artistic)abstract
- BACKGROUND: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.
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| 3. |
- Folkard, S, et al.
(author)
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Beyond the three-process model of alertness: estimating phase, time on shift, and successive night effects
- 1999
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In: Journal of biological rhythms. - : SAGE Publications. - 0748-7304 .- 1552-4531. ; 14:6, s. 577-587
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Journal article (peer-reviewed)abstract
- This paper starts by summarizing the development and refinement of the additive three-process model of alertness first published by Folkard and Åkerstedt in 1987. It reviews some of the successes that have been achieved by the model in not only predicting variations in subjective alertness on abnormal sleep-wake schedules but also in accounting for objective measures of sleep latency and duration. Nevertheless, predictions derived from the model concerning alertness on different shifts, and over successive night shifts, are difficult to reconcile with published data on accident risk. In light of this, we have examined two large sets of alertness ratings with a view to further refining the model and identifying additional factors that may influence alertness at any given point in time. Our results indicate that, at least for the range of sleep durations and wake-up times commonly found on rotating shift systems, we may assume the phase of the endogenous circadian component of alertness (process C) to be “set” by the time of waking. Such an assumption considerably enhanced the predictive power of the model and yielded remarkably similar phase estimates to those obtained by maximizing the post-hoc fit of the model. We then examined the manner in which obtained ratings differed from predicted values over a complete 8-day cycle of two, 12-h shift systems. This revealed a pronounced “first night compensation effect” that resulted in shift workers rating themselves as progressively more alert than would be predicted over the course of the first night shift. However, this appeared to be achieved only at the cost of lowered ratings on the second night shift. Finally, we were able to identify a “time on shift” effect whereby, with the exception of the first night shift, alertness ratings decreased over the course of each shift before showing a modest “end effect.” We conclude that the identification of these additional components offers the possibility that in the future we may be able to predict trends in accident risk on abnormal sleep-wake schedules.
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