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61.
Andreas Schmitt André Reimer Bernhard Kulzer Andrea Icks Rainer Paust Klaus-Martin Roelver Matthias Kaltheuner Dominic Ehrmann Michael Krichbaum Thomas Haak Norbert Hermanns 《Journal of diabetes and its complications》2018,32(4):384-392
Aims
To develop a psychometric measure of diabetes acceptance.Methods
An item pool was developed and pilot-tested using a sample of 220 people with diabetes; item selection resulted in the 20-item ‘Diabetes Acceptance Scale (DAS)’. 606 people with diabetes were then cross-sectionally assessed with the DAS to evaluate its reliability, validity and clinical utility; concurrent measurements included diabetes-related coping (FQCI), diabetes distress (PAID-5), depressive symptoms (PHQ-9), quality of life (EQ-5D), self-management (DSMQ), glycaemic control (HbA1c) and complications.Results
Internal reliability was high (Cronbach's α?=?0.96). Factorial and criterion-related results supported validity. Higher diabetes acceptance scores correlated with more functional coping styles, lower distress and depression levels, higher treatment adherence, better glycaemic control and better quality of life (all P?<?.001). Persons with low diabetes acceptance (22% of the sample) were four times more likely to have HbA1c values over 9.0% (75?mmol/mol), two times more likely to be diagnosed with long-term complications and each over two times more likely to have had episodes of severe hypoglycaemia and ketoacidosis in the past year; the prevalence of major depression in this group was fivefold increased (all P?<?.05).Conclusions
The DAS is a reliable and valid tool to measure diabetes acceptance. It may help identify patients with significant problems of accepting diabetes, a putative high-risk group in need of tailored care and support. 相似文献62.
Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors 下载免费PDF全文
Okumoto S Looger LL Micheva KD Reimer RJ Smith SJ Frommer WB 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(24):8740-8745
Glutamate is the predominant excitatory neurotransmitter in the mammalian brain. Once released, its rapid removal from the synaptic cleft is critical for preventing excitotoxicity and spillover to neighboring synapses. Despite consensus on the role of glutamate in normal and disease physiology, technical issues limit our understanding of its metabolism in intact cells. To monitor glutamate levels inside and at the surface of living cells, genetically encoded nanosensors were developed. The fluorescent indicator protein for glutamate (FLIPE) consists of the glutamate/aspartate binding protein ybeJ from Escherichia coli fused to two variants of the green fluorescent protein. Three sensors with lower affinities for glutamate were created by mutation of residues peristeric to the ybeJ binding pocket. In the presence of ligands, FLIPEs show a concentration-dependent decrease in FRET efficiency. When expressed on the surface of rat hippocampal neurons or PC12 cells, the sensors respond to extracellular glutamate with a reversible concentration-dependent decrease in FRET efficiency. Depolarization of neurons leads to a reduction in FRET efficiency corresponding to 300 nM glutamate at the cell surface. No change in FRET was observed when cells expressing sensors in the cytosol were superfused with up to 20 mM glutamate, consistent with a minimal contribution of glutamate uptake to cytosolic glutamate levels. The results demonstrate that FLIPE sensors can be used for real-time monitoring of glutamate metabolism in living cells, in tissues, or in intact organisms, providing tools for studying metabolism or for drug discovery. 相似文献
63.
van Gils FC; van Teeffelen ME; Neelis KJ; Hendrikx J; Burger H; van Leen RW; Knol E; Wagemaker G; Wognum AW 《Blood》1995,86(2):592-597
To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells. 相似文献
64.
Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B 总被引:3,自引:1,他引:3
In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B. 相似文献
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69.
Marianne Brodmann Martin Werner Dirk-Roelfs Meyer Peter Reimer Karsten Krüger Juan F. Granada Michael R. Jaff Henrik Schroeder 《JACC: Cardiovascular Interventions》2018,11(23):2357-2364
Objectives
The aim of this study was to assess the safety and effectiveness of a next-generation low-dose drug-coated balloon (DCB) designed to optimize the amount of drug transferred into the vessel wall and to maximize the amount of time the drug resides in the vessel wall.Background
Several randomized controlled studies evaluating various DCBs have demonstrated a significantly higher patency rate compared with noncoated percutaneous transluminal angioplasty balloons at 1 year. However, the data are limited and vary by DCB at longer follow-up time points. An earlier generation low-dose DCB failed to demonstrate significant treatment effect at 2 years, raising questions regarding the durability of low-dose DCBs.Methods
In this prospective, multicenter trial, 294 patients were randomized (3:1) to treatment with a DCB or an uncoated percutaneous transluminal angioplasty balloon. Assessments at 2 years included primary patency with duplex ultrasonography, clinically driven target lesion revascularization, and functional outcomes.Results
Primary patency at 2 years was significantly higher in the DCB cohort (75.9% vs. 61.0%; p = 0.025), and the rate of clinically driven target lesion revascularization was significantly lower (12.1% vs. 30.5%; p < 0.001). There were no major limb amputations in either group. The rates of all-cause (6.5% vs. 5.1%; p = 1.00) and cardiovascular-related (1.6% vs. 1.7%; p = 1.00) mortality were similar between groups. Functional improvements over baseline were sustained in both groups, with 60% fewer reinterventions in the DCB group.Conclusions
A sustained treatment effect is achievable with a low-dose DCB with an optimized coating formulation. This trial demonstrated for the first time a statistically significantly higher primary patency rate for a low-dose DCB versus PTA at 2 years. (CVI Drug Coated Balloon European Randomized Clinical Trial; NCT01858363) 相似文献70.
Matthias Christgen MD PhD Oleg Gluz MD Nadia Harbeck MD Ronald E. Kates PhD Mieke Raap MD Henriette Christgen Michael Clemens MD Wolfram Malter MD Benno Nuding MD Bahriye Aktas MD Sherko Kuemmel MD Toralf Reimer MD Andrea Stefek MD Petra Krabisch MD Marianne Just MD Doris Augustin MD Monika Graeser MD Frederick Baehner MD Rachel Wuerstlein MD Ulrike Nitz MD Hans Kreipe MD the West German Study Group PlanB Investigators 《Cancer》2020,126(22):4847-4858