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301.
Renegar G Webster CJ Stuerzebecher S Harty L Ide SE Balkite B Rogalski-Salter TA Cohen N Spear BB Barnes DM Brazell C 《Bioethics》2006,20(1):24-36
This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non-validated or hypothesis-generating). There is, however, a trend for research participants to be permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico-legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer 'Points-to-Consider' regarding returning results in the context of drug development trials based on their knowledge and experience. Theses considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit-to-risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies. 相似文献
302.
Duchniewicz M Zemojtel T Kolanczyk M Grossmann S Scheele JS Zwartkruis FJ 《Molecular and cellular biology》2006,26(2):643-653
Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rap1 in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1-/- cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins. 相似文献
303.
Budny B Chen W Omran H Fliegauf M Tzschach A Wisniewska M Jensen LR Raynaud M Shoichet SA Badura M Lenzner S Latos-Bielenska A Ropers HH 《Human genetics》2006,120(2):171-178
We report on a large family in which a novel X-linked recessive mental retardation (XLMR) syndrome comprising macrocephaly and ciliary dysfunction co-segregates with a frameshift mutation in the OFD1 gene. Mutations of OFD1 have been associated with oral–facial–digital type 1 syndrome (OFD1S) that is characterized by X-chromosomal dominant inheritance and lethality in males. In contrast, the carrier females of our family were clinically inconspicuous, and the affected males suffered from severe mental retardation, recurrent respiratory tract infections and macrocephaly. All but one of the affected males died from respiratory problems in infancy; and impaired ciliary motility was confirmed in the index patient by high-speed video microscopy examination of nasal epithelium. This family broadens the phenotypic spectrum of OFD1 mutations in an unexpected way and sheds light on the complexity of the underlying disease mechanisms.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at . 相似文献
304.
305.
Kang MS Besser TE Hancock DD Porwollik S McClelland M Call DR 《Applied and environmental microbiology》2006,72(11):6938-6947
Genetic elements specific to recent and contemporary epidemic strains of Salmonella enterica were identified using comparative genomic analysis. Two epidemic multidrug-resistant (MDR) strains, MDR Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) and cephalosporin-resistant MDR Salmonella enterica serovar Newport, and an epidemic pansusceptible strain, Salmonella serovar Typhimurium DT160, were subjected to Salmonella gene microarray and suppression subtractive hybridization analyses. Their genome contents were compared with those of coexisting sporadic strains matched by serotype, geographic and temporal distribution, and host species origin. These paired comparisons revealed that epidemic strains of S. enterica had specific genes and gene regions that were shared by isolates of the same subtype. Most of these gene sequences are related to mobile genetic elements, including phages, plasmids, and plasmid-like and transposable elements, and some genes may encode proteins conferring growth or survival advantages. The emergence of epidemic MDR strains may therefore be associated with the presence of fitness-associated genetic factors in addition to their antimicrobial resistance genes. 相似文献
306.
307.
Sukhorukov VL Reuss R Endter JM Fehrmann S Katsen-Globa A Gessner P Steinbach A Müller KJ Karpas A Zimmermann U Zimmermann H 《Biochemical and biophysical research communications》2006,346(3):829-839
Electrofusion of tumour and dendritic cells (DCs) is a promising approach for production of DC-based anti-tumour vaccines. Although human DCs are well characterised immunologically, little is known about their biophysical properties, including dielectric and osmotic parameters, both of which are essential for the development of efficient electrofusion protocols. In the present study, human DCs from the peripheral blood along with a tumour cell line used as a model fusion partner were examined by means of time-resolved cell volumetry and electrorotation. Based on the biophysical cell data, the electrofusion protocol could be rapidly optimised with respect to the sugar composition of the fusion medium, duration of hypotonic treatment, frequency range for stable cell alignment, and field strengths of breakdown pulses triggering membrane fusion. The hypotonic electrofusion consistently gave a tumour-DC hybrid rate of up to 19%, as determined by counting dually labelled fluorescent hybrids in a microscope. This fusion rate is nearly twice as high as that usually reported in the literature for isotonic media. The experimental findings and biophysical approach presented here are generally useful for the development of efficient electrofusion protocols, especially for rare and valuable human cells. 相似文献
308.
Boetel T Bade S Schmidt MA Frey A 《Biochemical and biophysical research communications》2006,349(1):296-302
The biological function of prion protein (PrP) and the physiological relevance of its truncated subtypes and glycoforms is still enigmatic. In this paper, we adduce evidence that recombinant murine PrP fragment 90-231 (mPrP90-231) contains a biotin-mimicking sequence motif that causes binding of the bacterial protein streptavidin to mPrP90-231. As indicated by epitope mapping and proven by analysis of a deletion mutant (mPrP101-231), streptavidin binding is primarily mediated by the amino-terminus of mPrP90-231 with the core-binding sequence represented by residues 94-100. Competition with biotin significantly reduces the interaction pointing to an involvement of streptavidin's biotin-binding site (BBS). Since the BBS of streptavidin shares similarities with the active sites of proteins involved in biotin metabolism we speculate that biotin mimicry by truncated PrP-species may have an impact in vivo. 相似文献
309.
Neumann K Michaux J Lebedev V Yigit N Colak E Ivanova N Poltoraus A Surov A Markov G Maak S Neumann S Gattermann R 《Molecular phylogenetics and evolution》2006,39(1):135-148
Despite some popularity of hamsters as pets and laboratory animals there is no reliable phylogeny of the subfamily Cricetinae available so far. Contradicting views exist not only about the actual number of species but also concerning the validity of several genera. We used partial DNA sequences of two mitochondrial (cytochrome b, 12S rRNA) and one partial nuclear gene (von Willebrand Factor exon 28) to provide a first gene tree of the Cricetinae based on 15 taxa comprising six genera. According to our data, Palaearctic hamsters fall into three distinct phylogenetic groups: Phodopus, Mesocricetus, and Cricetus-related species which evolved during the late Miocene about 7-12MY ago. Surprisingly, the genus Phodopus, which was previously thought to have appeared during the Pleistocene, forms the oldest clade. The largest number of extant hamster genera is found in a group of Cricetus-related hamsters. The genus Cricetulus itself proved to be not truly monophyletic with Cricetulus migratorius appearing more closely related to Tscherskia, Cricetus, and Allocricetulus. We propose to place the species within a new monotypic genus. Molecular clock calculations are not always in line with the dating of fossil records. DNA based divergence time estimates as well as taxonomic relationships demand a reevaluation of morphological characters previously used to identify fossils and extant hamsters. 相似文献
310.
Steffen Klamt Julio Saez-Rodriguez Jonathan A Lindquist Luca Simeoni Ernst D Gilles 《BMC bioinformatics》2006,7(1):56-26