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71.
Freites JA Tobias DJ von Heijne G White SH 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(42):15059-15064
Voltage-sensitive ion channels open and close in response to changes in transmembrane (TM) potential caused by the motion of the S4 voltage sensors. These sensors are alpha-helices that include four or more positively charged amino acids, most commonly arginine. The so-called paddle model, based on the high-resolution structure of the KvAP K+ channel [Jiang, et al. (2003) Nature 423, 33-41], posits that the S4 sensors move within the membrane bilayer in response to TM voltage changes. Direct exposure of S4 sensors to lipid is contrary to the classical expectation that the dielectric contrast between the membrane hydrocarbon core and water presents an insurmountable energetic penalty to burial of electric charges. Nevertheless, recent experiments have shown that a helix with the sequence of KvAP S4 can be inserted across the endoplasmic reticulum membrane. To reconcile this result with the classical energetics argument, we have carried out a molecular dynamics simulation of an isolated TM S4 helix in a lipid bilayer. The simulation reveals a stabilizing hydrogen-bonded network of water and lipid phosphates around the arginines that reduces the effective thickness of the bilayer hydrocarbon core to approximately 10 A in the vicinity of the helix. It suggests that bilayer phospholipids can adapt locally to strongly perturbing protein elements, causing the phospholipids to become a structural extension of the protein. 相似文献
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Thorsten Derlin Sebastian Schmuck Cathleen Juhl Steffi Teichert Johanna Zörgiebel Hans-Jürgen Wester Sophie M. Schneefeld Almut C. A. Walte James T. Thackeray Tobias L. Ross Frank M. Bengel 《Molecular imaging and biology》2018,20(4):650-658
Purpose
[68Ga]Trishydroxypyridinone (THP)–prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [68Ga]THP-PSMA.Procedures
[68Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [68Ga]PSMA I&T.Results
Physiologic uptake of [68Ga]THP-PSMA was significantly lower in salivary glands (P?<?0.0001), liver (P?<?0.0001), spleen (P?<?0.0001), and kidneys (P?<?0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T.Conclusion
[68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [68Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.75.
Teresa Trenkwalder Anna Lena Lahmann Magdalena Nowicka Costanza Pellegrini Tobias Rheude N. Patrick Mayr Stephanie Voss Sabine Bleiziffer Rüdiger Lange Michael Joner Albert M. Kasel Adnan Kastrati Heribert Schunkert Oliver Husser Martin Hadamitzky Christian Hengstenberg 《The international journal of cardiovascular imaging》2018,34(6):985-992
Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients’ outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80?±?7 vs. 80?±?7 years; p?=?0.198) and EuroSCORE II (3.6% [2.1–5.7] vs. 3.6% [2.1–5.9]; p?=?0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p?<?0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p?=?0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n?=?48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p?=?0.339, 1-year: 11% vs. 14%; p?=?0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality. 相似文献
76.
Charles J. Weschler Gabriel Bek? Holger M. Koch Tunga Salthammer Tobias Schripp J?rn Toftum Geo Clausen 《Environmental health perspectives》2015,123(10):928-934
Background
Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake of phthalate esters.Objectives
This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans.Methods
In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, corrected for background and hood air exposures.Results
For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m3 in air) compared with an inhalation intake of 3.8 μg/(μg/m3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m3 in air) compared with an inhalation intake of 3.9 μg/(μg/m3 in air).Conclusions
This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile organic compounds (SVOCs) whose molecular weight and lipid/air partition coefficient are in the appropriate range, direct absorption from air is also anticipated to be significant.Citation
Weschler CJ, Bekö G, Koch HM, Salthammer T, Schripp T, Toftum J, Clausen G. 2015. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verification. Environ Health Perspect 123:928–934; http://dx.doi.org/10.1289/ehp.1409151 相似文献77.
Heather Olson Tiffany Rudloe Tobias Loddenkemper Marvin B. Harper Amir A. Kimia 《The American journal of emergency medicine》2018,36(8):1386-1390
Background and aims
Children with first complex febrile seizure (CFS) are often admitted for observation. The goals of this study were 1) to assess the risk of seizure recurrence during admission, 2) to determine whether early EEG affects acute management.Design/methods
We retrospectively reviewed a cohort of children 6–60 months of age admitted from a Pediatric Emergency Department for first CFS over a 15 year period. We excluded children admitted for supportive care of their febrile illness. Data extraction included age, gender, seizure features, laboratory and imaging studies, EEG, further seizures during admission, and antiepileptic drugs (AEDs) given.Results
One hundred eighty three children met inclusion criteria. Seven patients had seizures during the admission (7/183 or 3.8%) Since 38 children were loaded with anti-epileptic medication during their visit, the adjusted rate is 7/145 or 4.8.Increased risk of seizure recurrence during admission was observed in children presenting with multiple seizures (P = 0.005).EEG was performed in 104/183 children (57%) and led to change in management in one patient (1%, 95% C.I. 0.05–6%). Six of the 7 children with seizure had an EEG. The study was normal in 3 and findings in the other 2 did not suggest/predict further seizures during the admission.Conclusions
Children with first CFSs are at low risk for seizure recurrence during admission. Multiple seizures at presentation are associated with risk of early recurrence and may warrant an admission. EEG had limited effect on acute management and should not be an indication for admission. 相似文献78.
79.
Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits 下载免费PDF全文
80.
Weidner Kathrin Behnes Michael Schupp Tobias Hoppner Jorge Ansari Uzair Mueller Julian Lindner Simon Borggrefe Martin Kim Seung-hyun Huseyinov Aydin Ellguth Dominik Akin Muharrem Meininghaus Dirk Große Bertsch Thomas Taton Gabriel Bollow Armin Reichelt Thomas Engelke Niko Reiser Linda Akin Ibrahim 《Journal of interventional cardiac electrophysiology》2022,63(1):13-20
Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a... 相似文献