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排序方式: 共有290条查询结果,搜索用时 21 毫秒
91.
Mathews WB Scheffel U Finley P Ravert HT Frank RA Rinaldi-Carmona M Barth F Dannals RF 《Nuclear medicine and biology》2000,27(8):757-762
ABSTRACT. [18F] SR144385 and [18F] SR147963 were synthesized in a multistep reaction in which fluorine-18 was introduced by nucleophilic halogen displacement on a bromo precursor. The fluorine-18-labeled intermediate was deprotected and coupled with the appropriate alkyl amine to give the final products. Both radioligands had appropriate regional brain distribution for cannabinoid receptors with a target to nontarget ratio of 1.7 for [18F] SR147963 and 2.5 for [18F] SR144385 at 60 and 90 min postinjection, respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A. 相似文献
92.
Andrew G. Horti Hayden T. Ravert Yongjun Gao Daniel P. Holt William H. Bunnelle Michael R. Schrimpf Tao Li Jianguo Ji Heather Valentine Ursula Scheffel Hiroto Kuwabara Dean F. Wong Robert F. Dannals 《Nuclear medicine and biology》2013,40(3):395-402
Introductionα7-nicotinic acetylcholine receptor (α7-nAChR) is one of the major neuronal nAChR subtypes. α7-nAChR is involved in variety of neuronal processes and disorders including schizophrenia and Alzheimer's disease. A number of α7-nAChR PET radioligands have been developed, but a quality radiotracer remains to be discovered.MethodsHigh binding affinity α7-nAChR ligands A-833834 and A-752274 were radiolabeled with 11C. Baseline and blockade biodistribution studies in the mouse brain of [11C]A-833834 (5-(6-(5-[11C]methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-1H-indole) and [11C]A-752274 (2-(6-[11C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)-7-(6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)-9H-fluoren-9-one) were performed. [11C]A-752274 was evaluated in a baseline baboon PET study.Results[11C]A-833834 and [11C]A-752274 were synthesized by radiomethylation of corresponding des-methyl precursors. The radioligands were prepared with radiochemical yield of 12%–32%, high specific radioactivity (330–403 GBq/μmol) and radiochemical purity > 95%. Dissection studies with [11C]A-833834 demonstrated low specific α7-nAChR binding in the mouse brain. [11C]A-752274 specifically (~ 50%) labeled α7-nAChR in the mouse thalamus. However, [11CA-752274 exhibited low brain uptake in baboon (%SUV < 100).ConclusionTwo novel α7-nAChR ligands radioligands were synthesized and studied in animals. Specific binding of [11C]A-833834 in the mouse brain is low due to the insufficient binding affinity of the radioligand. The very high binding affinity [11C]A-752274 exhibited good specific binding in the α7-nAChR-rich mouse brain regions. The low uptake of [11C]A-752274 in the baboon brain is due to its high hydrophilicity, rapid metabolism or other properties. Future development of α7-nAChR PET radioligands will be based on compounds with high binding affinities and good blood–brain barrier permeability. 相似文献
93.
Scheffel A Poulsen N Shian S Kröger N 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(8):3175-3180
Diatoms are eukaryotic microalgae that produce species-specifically structured cell walls made of SiO(2) (silica). Formation of the intricate silica structures of diatoms is regarded as a paradigm for biomolecule-controlled self-assembly of three-dimensional, nano- to microscale-patterned inorganic materials. Silica formation involves long-chain polyamines and phosphoproteins (silaffins and silacidins), which are readily soluble in water, and spontaneously form dynamic supramolecular assemblies that accelerate silica deposition and influence silica morphogenesis in vitro. However, synthesis of diatom-like silica structure in vitro has not yet been accomplished, indicating that additional components are required. Here we describe the discovery and intracellular location of six novel proteins (cingulins) that are integral components of a silica-forming organic matrix (microrings) in the diatom Thalassiosira pseudonana. The cingulin-containing microrings are specifically associated with girdle bands, which constitute a substantial part of diatom biosilica. Remarkably, the microrings exhibit protein-based nanopatterns that closely resemble characteristic features of the girdle band silica nanopatterns. Upon the addition of silicic acid the microrings become rapidly mineralized in vitro generating nanopatterned silica replicas of the microring structures. A silica-forming organic matrix with characteristic nanopatterns was also discovered in the diatom Coscinodiscus wailesii, which suggests that preassembled protein-based templates might be general components of the cellular machinery for silica morphogenesis in diatoms. These data provide fundamentally new insight into the molecular mechanisms of biological silica morphogenesis, and may lead to the development of self-assembled 3D mineral forming protein scaffolds with designed nanopatterns for a host of applications in nanotechnology. 相似文献
94.
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96.
随着对一些疾病日节律性的研究加深,时辰药物治疗越来越受到重视。为此本文从高血压、肿瘤、哮喘等治疗药入手,对相关时辰药物治疗的情况作一综述。 相似文献
97.
Cook C Gendron TF Scheffel K Carlomagno Y Dunmore J DeTure M Petrucelli L 《Human molecular genetics》2012,21(13):2936-2945
The abnormal accumulation of the microtubule-binding protein tau is associated with a number of neurodegenerative conditions, and correlates with cognitive decline in Alzheimer's disease. The ubiquitin ligase carboxy terminus of Hsp70-interacting protein (CHIP) and the molecular chaperone Hsp90 are implicated in protein triage decisions involving tau, and have consequently been targeted for therapeutic approaches aimed at decreasing tau burden. Here, we present evidence that CHIP binds, ubiquitinates and regulates expression of histone deacetylase 6 (HDAC6). As the deacetylase for Hsp90, HDAC6 modulates Hsp90 function and determines the favorability of refolding versus degradation of Hsp90 client proteins. Moreover, we demonstrate that HDAC6 levels positively correlate with tau burden, while a decrease in HDAC6 activity or expression promotes tau clearance. Consistent with previous research on Hsp90 clients in cancer, we provide evidence that a loss of HDAC6 activity augments the efficacy of an Hsp90 inhibitor and drives client degradation, in this case tau. Therefore, our current findings not only identify HDAC6 as a critical factor for the regulation of tau levels, but also indicate that a multi-faceted treatment approach could more effectively arrest tau accumulation in disease. 相似文献
98.
Paul Stolzmann Hatem Alkadhi Hans Scheffel Anja Hennemuth Caroline Kuehnel Stephan Baumueller Sebastian Kozerke Volkmar Falk Borut Marincek Olivio F. Donati 《European radiology》2010,20(5):1174-1179
Objective
To develop a tool for the image fusion of computed tomography coronary angiography (CTCA) and cardiac magnetic resonance imaging (CMR). 相似文献99.
Gudrun Feuchtner Robert Götti Andrè Plass Stephan Baumueller Paul Stolzmann Hans Scheffel Monika Wieser Borut Marincek Hatem Alkadhi Sebastian Leschka 《European radiology》2010,20(9):2092-2099
Purpose
To describe prospective ECG-triggered dual-source CT dual-step pulsing (pECGdual_step) for evaluation of coronary arteries and cardiac function.Methods
Fifty-one consecutive patients pre- or post-cardiovascular surgery were examined with adaptive sequential tube current modulated (pECGdual-step) 128-slice dual-source CT without heart rate control (main padding window: 40% RR interval?>65 bpm/70% RR interval?<65 bpm). Image quality of coronary arteries was graded (4-point scale), and cardiac function was evaluated.Results
Mean HR was 68 bpm. Thirty-seven patients were in stable sinus rhythm (SR); 14 had arrhythmia. Image quality of coronary arteries was diagnostic in 804/816 (98%) of segments. The number of non-diagnostic segments was higher in patients with arrhythmia as compared to those in SR (4% vs. 0.5%; p?=?0.01), and there were fewer segments with excellent image quality (79% vs. 94%; p?<?0.001) and more segments with impaired image quality (p?<?0.001 and p?=?0.002). Global and regional LV function could be evaluated in 41 (80%) and 47 (92%) patients, and valvular function in 48 (94%). In 11/14 of patients with arrhythmia, the second step switched to full mAs, increasing radiation exposure to 8.6 mAs (p?<?0.001). The average radiation dose was 3.8 mSv (range, 1.7–7.9) in patients in SR.Conclusion
pECGdual-step128-slice DSCT is feasible for the evaluation of coronary arteries and cardiac function without heart rate control in patients in stable sinus rhythm at a low radiation dose. 相似文献100.
Thomas Frauenfelder Philippe Appenzeller Christoph Karlo Hans Scheffel Lotus Desbiolles Paul Stolzmann Borut Marincek Hatem Alkadhi Thomas Schertler 《European radiology》2009,19(4):789-799
Triage decisions in patients suffering from acute chest pain remain a challenge. The patient’s history, initial cardiac enzyme
levels, or initial electrocardiograms (ECG) often do not allow selecting the patients in whom further tests are needed. Numerous
vascular and non-vascular chest problems, such as pulmonary embolism (PE), aortic dissection, or acute coronary syndrome,
as well as pulmonary, pleural, or osseous lesions, must be taken into account. Nowadays, contrast-enhanced multi-detector-row
computed tomography (CT) has replaced previous invasive diagnostic procedures and currently represents the imaging modality
of choice when the clinical suspicion of PE or acute aortic syndrome is raised. At the same time, CT is capable of detecting
a multitude of non-vascular causes of acute chest pain, such as pneumonia, pericarditis, or fractures. Recent technical advances
in CT technology have also shown great advantages for non-invasive imaging of the coronary arteries. In patients with acute
chest pain, the optimization of triage decisions and cost-effectiveness using cardiac CT in the emergency department have
been repetitively demonstrated. Triple rule-out CT denominates an ECG-gated protocol that allows for the depiction of the
pulmonary arteries, thoracic aorta, and coronary arteries within a single examination. This can be accomplished through the
use of a dedicated contrast media administration regimen resulting in a simultaneous attenuation of the three vessel territories.
This review is intended to demonstrate CT parameters and contrast media administration protocols for performing a triple rule-out
CT and discusses radiation dose issues pertinent to the protocol. Typical life-threatening and non-life-threatening diseases
causing acute chest pain are illustrated. 相似文献