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1.
H. Riad A. Nicholls J. Neuberger S. M. Willatts R. A. Sells M. A. Jones R. Francis 《BMJ (Clinical research ed.)》1995,310(6981):714-718
Elective ventilation describes the procedure of transferring selected patients dying from rapidly progressive intracranial haemorrhage from general medical wards to intensive care units for a brief period of ventilation before confirmation of brain stem death and harvesting of organs. This approach in Exeter has led to a rate of kidney retrieval and transplant higher than has been achieved elsewhere in the United Kingdom, with a stabilisation of numbers on patients on dialysis. Recently doubt has been cast on the legality of our practice of elective ventilation on the grounds that relatives are not permitted to consent to treatment of an incompetent person when that treatment is not in the patient''s best interests. We are thus faced with the dilemma of a protocol that is ethical, practical, and operates for the greater good but which may be illegal. This article explores various objections to the protocol and calls for public, medical, and legal debate on the issues. 相似文献
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Ekkehard Lindner Walter Wassing Markus W. Pitsch Riad Fawzi Manfred Steimann 《Inorganica chimica acta》1994,220(1-2):107-113
The reaction of the bis(triflates) 1,2-bis[2-(trifluoromethylsulfonyloxy)ethyl]benzene (1), 1,2-bis[3-(trifluoromethylsulfonyloxy)propyl]benzene (3) and 1,2-bis{2-[2-(trifluoromethylsulfonyloxy)ethyl]phenyl}ethane (6), respectively, with the carbonyl metalates [M(CO)4]2- (M=Os (a), Ru (b), Fe (c)) results in the formation of the osmaorthocyclophanes 2a, 4a, 7a and 8a, the ruthenacylophane 2b and the ferracyclophanes 2c and 7c, respectively. Carbon monoxide insertion into the Fe-Cσ bonds of the ferracycles 2c and 7c, respectively, affords the ketones 3-oxo[5]orthocyclophane (9) and 3-oxo[5.2]orthocyclophane (11). The structure of 2a was investigated by an X-ray structural analysis. 2a crystallizes in the monoclinic space group P21/n with Z=4. 相似文献
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Klara Ivankova Rostislav Turecek Thorsten Fritzius Riad Seddik Laurent Prezeau La?titia Comps-Agrar Jean-Philippe Pin Bernd Fakler Valerie Besseyrias Martin Gassmann Bernhard Bettler 《The Journal of biological chemistry》2013,288(34):24848-24856
GABAB receptors are the G-protein coupled receptors (GPCRs) for GABA, the main inhibitory neurotransmitter in the central nervous system. Native GABAB receptors comprise principle and auxiliary subunits that regulate receptor properties in distinct ways. The principle subunits GABAB1a, GABAB1b, and GABAB2 form fully functional heteromeric GABAB(1a,2) and GABAB(1b,2) receptors. Principal subunits regulate forward trafficking of the receptors from the endoplasmic reticulum to the plasma membrane and control receptor distribution to axons and dendrites. The auxiliary subunits KCTD8, -12, -12b, and -16 are cytosolic proteins that influence agonist potency and G-protein signaling of GABAB(1a,2) and GABAB(1b,2) receptors. Here, we used transfected cells to study assembly, surface trafficking, and internalization of GABAB receptors in the presence of the KCTD12 subunit. Using bimolecular fluorescence complementation and metabolic labeling, we show that GABAB receptors associate with KCTD12 while they reside in the endoplasmic reticulum. Glycosylation experiments support that association with KCTD12 does not influence maturation of the receptor complex. Immunoprecipitation and bioluminescence resonance energy transfer experiments demonstrate that KCTD12 remains associated with the receptor during receptor activity and receptor internalization from the cell surface. We further show that KCTD12 reduces constitutive receptor internalization and thereby increases the magnitude of receptor signaling at the cell surface. Accordingly, knock-out or knockdown of KCTD12 in cultured hippocampal neurons reduces the magnitude of the GABAB receptor-mediated K+ current response. In summary, our experiments support that the up-regulation of functional GABAB receptors at the neuronal plasma membrane is an additional physiological role of the auxiliary subunit KCTD12. 相似文献
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There are two highly homologous survival motor neuron (SMN) genes in humans but molecular defects in the SMN1 gene cause spinal muscular atrophy (SMA). More than 90% of SMA patients are shown to have a homozygous deletion of exon 7 in the SMN1 gene. Therefore, a simple test for exon 7 deletion would be very useful in the molecular diagnosis of SMA. However, limited methods are available, and most of these methods utilize expensive instruments and consumables. Here, we describe a simple allele-specific PCR test, which can be performed using standard equipment in DNA laboratories. The principle of the test is based on a single nucleotide difference (C versus T) between the exon 7 of SMN1 and SMN2 genes. Using allele-specific primers, two PCR amplifications are performed for each sample to amplify a 404-bp diagnostic fragment, and consequent electrophoresis of PCR products on agarose gel provides definitive information concerning the exon 7 deletion To rule out false negatives, a 500-bp fragment from the N-acetyltransferase gene was coamplified as an internal control in each test. We have, so far, analyzed 41 SMA samples with our method, and tested the validity of results using an independent restriction fragment length polymorphism (RFLP) method. Genotyping results obtained by both methods were in complete agreement for all of the samples analyzed. Our method can also be used to detect heterozygous deletion of exon 7 in SMN genes, if the relative intensities of the diagnostic and internal control bands are determined. 相似文献
7.
Al-Yahyaee S Gaffar U Al-Ameri MM Qureshi M Zadjali F Ali BH Bayoumi R 《Human biology; an international record of research》2007,79(4):445-452
Interindividual and interethnic differences in allele frequencies of N-acetyltransferase (NAT2) single nucleotide polymorphisms (SNPs) are responsible for phenotypic variability of adverse drug reactions and susceptibility to cancer. We genotyped the seven NAT2 common SNPs in 127 randomly selected unrelated northern Sudanese subjects using allele-specific and RFLP polymerase chain reaction (PCR) based methods. Molecular genotyping was enough to designate alleles for 41 individuals unambiguously, whereas 63 individuals' alleles were inferred from haplotypes previously described. In the remaining 23 individuals, however, the phase of the SNPs could not be decided because of multiple SNP heterozygotes. Using computational methods in the HAP and Phase programs, we confirmed the inferred alleles of the 62 individuals and predicted the remaining 23 ambiguous alleles. Twelve NAT2 alleles were identified. Four alleles coded for rapid acetylators (18%), and eight alleles coded for slow acetylators (82%). Two genotypes coded for rapid acetylation (3.9%), 10 for intermediate acetylation (27.6%), and 13 for slow acetylation (68.5%). The G191A African SNP and the G857A predominantly Asian SNP were each detected at a low frequency of 3.1%. The combination of molecular and computational analysis was useful in resolving ambiguous genotypes of NAT2 in multiple SNP heterozygotes. Among the northern Sudanese the SNPs associated with slow acetylation are more prevalent than in Caucasians and Asians. This and other African studies are suggestive of an African origin for NAT2-associated polymorphism. 相似文献
8.
Efendiev R Chen Z Krmar RT Uhles S Katz AI Pedemonte CH Bertorello AM 《The Journal of biological chemistry》2005,280(16):16272-16277
Clathrin-dependent endocytosis of Na(+),K(+)-ATPase molecules in response to G protein-coupled receptor signals is triggered by phosphorylation of the alpha-subunit and the binding of phosphoinositide 3-kinase. In this study, we describe a molecular mechanism linking phosphorylation of Na(+),K(+)-ATPase alpha-subunit to binding and activation of phosphoinositide 3-kinase. Co-immunoprecipitation studies, as well as experiments using confocal microscopy, revealed that dopamine favored the association of 14-3-3 protein with the basolateral plasma membrane and its co-localization with the Na(+),K(+)-ATPase alpha-subunit. The functional relevance of this interaction was established in opossum kidney cells expressing a 14-3-3 dominant negative mutant, where dopamine failed to decrease Na(+),K(+)-ATPase activity and to promote its endocytosis. The phosphorylated Ser-18 residue within the alpha-subunit N terminus is critical for 14-3-3 binding. Activation of phosphoinositide 3-kinase by dopamine during Na(+),K(+)-ATPase endocytosis requires the binding of the kinase to a proline-rich domain within the alpha-subunit, and this effect was blocked by the presence of a 14-3-3 dominant negative mutant. Thus, the 14-3-3 protein represents a critical linking mechanism for recruiting phosphoinositide 3-kinase to the site of Na(+),K(+)-ATPase endocytosis. 相似文献
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Al-Kasasbeh R Korenevskiy N Ionescou F Alshamasin M Kuzmin A 《Computer methods in biomechanics and biomedical engineering》2012,15(7):681-689
Many theories of reflexology use ancient concepts which do not coincide with the modern medical terminology of anatomy, physiology and biophysics. This substantially reduces the trust of physicians in reflexology methods. During this research, several mathematical models for the interaction of the internal and biological active points of meridian structures have been proposed. The analysis of these models allows the specification of a list of heart diseases for which reflex diagnostics and reflex therapy methods are most effective and also allows increasing the effectiveness of these procedures. It is shown that good results for the prediction and early diagnosis of diseases from the reaction energy of biologically active points (acupuncture points) are obtained using fuzzy logic decision making. 相似文献
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Badawi AM Fahmy AA Mohamed KA Noor El-Din MR Riad MG 《Preparative biochemistry & biotechnology》2012,42(1):44-59
In this work, four nonionic surfactants based on sorbitan monolaurate (Span 20) were synthesized by introducing ethylene oxide gas (n?=?20, 40, 60, 80 ethylene oxide units) into Span 20 to give four new surfactants with different hydrophilic-lipophilic balance (HLB), namely, E(20), E(40), E(60), and E(80). The structures of the prepared nonionic surfactants were elucidated using Fourier-transform infrared (FT-IR) and (1)H-nuclear magnetic resonance (NMR) spectroscopy. The surface-tension measurements were recorded. The effects of the prepared nonionic surfactants on the simultaneous saccharification and fermentation (SSF) of microwave/alkali-pretreated rice straw to produce ethanol were investigated. From the obtained data, it was found that the addition of the nonionic surfactants at 2.5?g/L had a positive effect on SSF. The maximum ethanol yield (76 and 55%) was obtained after 72?hr for rice straw using Kluyveromyces marxianus and Saccharomyces cerevisiae, respectively. Also, it was found that the ethanol yield increases with increasing HLB of the prepared nonionic surfactants by increasing ethylene oxide units. The adsorption of nonionic surfactants on lignocelluloses is proposed to be due to hydrophobic and hydrogen bonding interactions between nonionic surfactants and the lignin part in the lignocelulose. It can be concluded that additions of surface-active compounds, such as nonionic surfactants, increase enzymatic conversion of rice straw for bioethanol purposes. 相似文献