PubMed Health⌕ Search

Biomedical subjects

S Dekker

Publications and source records attributed to S Dekker.

8 recordsLinked to original sources
PubMed2001

The ergonomics of flight management systems: fixing holes in the cockpit certification net.

Recent air traffic control regulations mandate the installation of computer-based flight management systems in airliners across Europe. Integrating and certifying add-on cockpit systems is a long and costly process, which in its current form cannot meaningfully address ergonomics aspects. Two levels of problems occur: add-on systems carry many "classic" HCI failures, which could easily be addressed with modified certification requirements. Further, adding new technology changes practice, creates new skill and knowledge demands and produces new forms of error, which are more difficult to assess in advance. However, one innovative certification approach for add-on cockpit systems, based on the use of a representative population of user pilots, was found to be promising. This method minimizes the subjective bias of individual pilots in addition to defining pass/fail criteria in an operational environment.

Aviation↗
PubMed2001

Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates.

In recent experiments, in which we compared hDAF transgenic rat hearts perfused with 15% human serum in the Langendorff device and hDAF rat hearts transplanted into cynomolgus monkeys, we demonstrated that in the ex vivo heart perfusion model both homozygous and heterozygous hDAF hearts survived longer as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments with rat heart xenografts. Secondly, we investigated whether the observed differences in survival times of rat xenografts between in vivo and ex vivo transplantation would also hold for mouse hearts transgenic for hDAF. An ex vivo model was used to perfuse hDAF mouse hearts and controls with human serum or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly longer than their controls when perfused with 15% human serum, but no difference was found when 30% human serum was used, or when these hearts were transplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNs adhering to the vascular endothelium was significantly lower in hDAF transgenes as compared with their controls. In conclusion, in the ex vivo situation, the efficacy of hDAF transgenesis in preventing HAR is limited by serum complement concentration.

Animals↗
PubMed1999

Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma.

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Cloning and sequencing of the CRABP-I locus from chicken and pufferfish: analysis of the promoter regions in transgenic mice.

Retinoic acid (RA), a derivative of vitamin A, is an important molecule for development and homeostasis of vertebrate organisms. The intracellular retinoic acid binding protein CRABP-I has a high affinity for RA, and is thought to be involved in the mechanism of RA signalling. CRABP-I is well conserved in evolution and shows a specific expression pattern during development, but mice made deficient for the protein by gene targeting appear normal. However, the high degree of homology with CRABP-I from other species indicates that the protein has been subject to strong selective conservation, indicative of an important biological function. In this paper we have compared the conservation in the expression pattern of the mouse, chicken and pufferfish CRABP-I genes to substantiate this argument further. First we cloned and sequenced genes and promoter regions of the CRABP-I genes from chicken and the Japanese pufferfish, Fugu rubripes. Sequence comparison with the mouse gene did not show any large blocks of homology in the promoter regions. Nevertheless, the promoter of the chicken gene directed expression to a subset of the tissues that show expression with the promoter from the mouse gene. The pattern observed with the pufferfish promoter is even more restricted, essentially to rhombomere 4 only, indicating that this region may be functionally the most important for CRABP-I expression in the developing embryo.

Amino Acid Sequence↗
PubMed1997

Regulation of the CRABP-I gene during mouse embryogenesis.

The cellular retinoic acid binding protein type I (CRABP-I) shows a highly specific expression pattern during mouse embryonic development. The tissues that express CRABP-I, i.e. the central nervous system (CNS), neural crest, branchial arches, limb bud and frontonasal mass, coincide with those that are most sensitive to unphysiological retinoic acid (RA) concentrations. We have investigated the transcriptional elements that are responsible for the spatiotemporal regulation of CRABP-I expression in the mouse embryo. We show here that a 16 kb fragment harbours all the elements needed for the correct spatiotemporal expression pattern. Upon further dissection of this fragment we have found that expression in the CNS is driven by elements in the upstream region of the gene, while expression in mesenchymal and neural crest tissue is regulated via element(s) located downstream of exon II of the gene. Two distinct fragments in the upstream region are required for expression in the CNS, as neither of these fragments alone is able to drive correct expression of a reporter gene in transgenic mice. DNAseI footprinting analysis of the two upstream fragments revealed the presence of a number of protected elements. One of these regulatory elements has the hallmarks of an RA response element, suggesting that CRABP-I expression in neural tissue can be directly modulated by RA via the RARs/RXRs.

Animals↗
PubMed1991

A single amino acid substitution changes the substrate specificity of quinoprotein glucose dehydrogenase in Gluconobacter oxydans.

Gluconobacter oxydans contains pyrroloquinoline quinone-dependent glucose dehydrogenase (GDH). Two isogenic G. oxydans strains, P1 and P2, which differ in their substrate specificity with respect to oxidation of sugars have been analysed. P1 can oxidize only D-glucose, whereas P2 is also capable of the oxidation of the disaccharide maltose. To investigate the nature of this maltose-oxidizing property we cloned the gene encoding GDH from P2. Expression of P2 gdh in P1 enables the latter strain to oxidize maltose, indicating that a mutation in the P2 gdh gene is responsible for the change in substrate specificity. This mutation could be ascribed to a 1 bp substitution resulting in the replacement of His 787 by Asn.

Amino Acid Sequence↗