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991.
Sphingosine kinases (SphKs), of which there are two isoforms, SphK1 and SphK2, have been implicated in regulation of many important cellular processes. We have developed an assay for monitoring SphK1 and SphK2 activity in real time without the need for organic partitioning of products, radioactive materials, or specialized equipment. The assay conveniently follows SphK-dependent changes in 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled sphingosine (Sph) fluorescence and can be easily performed in 384-well plate format with small reaction volumes. We present data showing dose-proportional responses to enzyme, substrate, and inhibitor concentrations. The SphK1 and SphK2 binding affinities for NBD-Sph and the IC50 values of inhibitors determined were consistent with those reported with other methods. Because of the versatility and simplicity of the assay, it should facilitate the routine characterization of inhibitors and SphK mutants and can be readily used for compound library screening in high-throughput format. 相似文献
992.
Anjani K. Tiwari Joji Yui Masayuki Fujinaga Katsushi Kumata Yoko Shimoda Tomoteru Yamasaki Lin Xie Akiko Hatori Jun Maeda Nobuki Nengaki Ming‐Rong Zhang 《Journal of neurochemistry》2014,129(4):712-720
We developed the novel positron emission tomography (PET) ligand 2‐[5‐(4‐[11C]methoxyphenyl)‐2‐oxo‐1,3‐benzoxazol‐3(2H)‐yl]‐N‐methyl‐N‐phenylacetamide ([11C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [11C]MBMP was synthesized by reacting desmethyl precursor ( 1 ) with [11C]CH3I in radiochemical purity of ≥ 98% and specific activity of 85 ± 30 GBq/μmol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO‐rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [11C]MBMP at 60 min after injection. To determine the specific binding of [11C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [11C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up‐regulation of microglia during neuroinflammation.
993.
M. J. Bom J. M. B. Manders R. Uijlings E. A. Badings F. M. A. C. Martens 《Netherlands heart journal》2014,22(4):151-157
Background
Single-photon emission computed tomography (SPECT) is an important prognostic tool in evaluating coronary artery disease (CAD), with a high negative predictive value (NPV) for the occurrence of major adverse cardiac events (MACE). The prognostic value of SPECT is disputed in women, patients with atrial fibrillation (AF), diabetes, left bundle branch block (LBBB) and renal impairment.Methods
Seven hundred sixty-two patients without prior history of CAD who had SPECT without perfusion deficits were followed for 2 years for MACE. Predictive variables for the occurrence of MACE were reviewed by Cox proportional hazard regression, considering clinical information, resting-ECG data and SPECT data.Results
The NPV of SPECT for the occurrence of MACE within 2 years was 95.8 %. Multivariate Cox regression revealed male gender as the only significant predictor for the occurrence of MACE, besides a positive stress ECG at SPECT and a low LVEF. AF, LBBB, renal impairment and diabetes had no significant effect on the prognosis after normal SPECT.Conclusion
SPECT with normal perfusion images has great NPV in a medium-sized clinic in the Netherlands, even in patients with LBBB, AF, diabetes and renal impairment. MACE-free survival, however, was negatively influenced by male gender; we therefore propose more caution in men. 相似文献994.
In Vitro and In Vivo Evaluation of N‐{2‐[4‐(3‐Cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[11C]methoxybenzamide,a Positron Emission Tomography (PET) Radioligand for Dopamine D4 Receptors,in Rodents 下载免费PDF全文
Marcello Leopoldo Svetlana V. Selivanova Adrienne Müller Enza Lacivita Simon M. Ametamey 《化学与生物多样性》2014,11(9):1298-1308
The D4 dopamine receptor belongs to the D2‐like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high‐affinity D4 receptor‐selective ligand N‐{2‐[4‐(3‐cyanopyridin‐2‐yl)piperazin‐1‐yl]ethyl}‐3‐[11C]methoxybenzamide ([11C] 2 ) in rat. The results provide new insights on the in vitro properties that a brain PET dopamine D4 radioligand should possess in order to have improved in vivo utility in rodents. 相似文献
995.
Brian N Jobse Cory AJR McCurry Mathieu C Morissette Rod G Rhem Martin R St?mpfli Nancy Renée Labiris 《Respiratory research》2014,15(1):42
Background
Chronic obstructive pulmonary disease (COPD) is known to greatly affect ventilation (V) and perfusion (Q) of the lung through pathologies such as inflammation and emphysema. However, there is little direct evidence regarding how these pathologies contribute to the V/Q mismatch observed in COPD and models thereof. Also, little is known regarding how smoking cessation affects V/Q relationships after inflammation and airspace enlargement have become established. To this end, we have quantified V/Q on a per-voxel basis using single photon emission computed tomography (SPECT) in mouse models of COPD and lung obstruction.Methods
Three distinct murine models were used to investigate the impact of different pathologies on V/Q, as measured by SPECT. Lipopolysaccharide (LPS) was used to produce neutrophilic inflammation, porcine pancreatic elastase (PPE) was used to produce emphysema, and long-term cigarette smoke (CS) exposure and cessation were used to investigate the combination of these pathologies.Results
CS exposure resulted in an increase in mononuclear cells and neutrophils, an increase in airspace enlargement, and an increase in V/Q mismatching. The inflammation produced by LPS was more robust and predominantly neutrophilic, compared to that of cigarette smoke; nevertheless, inflammation alone caused V/Q mismatching similar to that seen with long-term CS exposure. The emphysematous lesions caused by PPE administration were also capable of causing V/Q mismatch in the absence of inflammation. Following CS cessation, inflammatory cell levels returned to those of controls and, similarly, V/Q measures returned to normal despite evidence of persistent mild airspace enlargement.Conclusions
Both robust inflammation and extensive airspace enlargement, on their own, were capable of producing V/Q mismatch. As CS cessation resulted in a return of V/Q mismatching and inflammatory cell counts to control levels, lung inflammation is likely a major contributor to V/Q mismatch observed in the cigarette smoke exposure model as well as in COPD patients. This return of V/Q mismatching to control values also took place in the presence of mild airspace enlargement, indicating that emphysematous lesions must be of a larger volume before affecting the lung significantly. Early smoking cessation is therefore critical before emphysema has an irreversible impact on gas exchange. 相似文献996.
Phage mediated horizontal transfer of the sopE1 gene increases enteropathogenicity of Salmonella enterica serotype Typhimurium for calves 总被引:1,自引:0,他引:1
Zhang S Santos RL Tsolis RM Mirold S Hardt WD Adams LG Bäumler AJ 《FEMS microbiology letters》2002,217(2):243-247
Anaerobic fungi are an important component of the cellulolytic ruminal microflora. Ammonia alone as N source supports growth, but amino acid mixtures are stimulatory. In order to evaluate the extent of de novo synthesis of individual amino acids in Piromyces communis and Neocallimastix frontalis, isotope enrichment in amino acids was determined during growth on (15)NH(4)Cl in different media. Most cell N (0.78 and 0.63 for P. communis and N. frontalis, respectively) and amino acid N (0.73 and 0.59) continued to be formed de novo from ammonia when 1 g l(-1) trypticase was added to the medium; this concentration approximates the peak concentration of peptides in the rumen after feeding. Higher peptide/amino acid concentrations decreased de novo synthesis. Lysine was exceptional, in that its synthesis decreased much more than other amino acids when Trypticase or amino acids were added to the medium, suggesting that lysine synthesis might limit fungal growth in the rumen. 相似文献
997.
Matthias Zessner Adam Kovacs Christian Schilling Gerald Hochedlinger Oliver Gabriel Stephanie Natho Simon Thaler Georg Windhofer 《International Review of Hydrobiology》2011,96(5):541-560
Mountainous catchments are usually not in focus of the modelling of nutrient fluxes on catchment scale. Out of 9 model approaches tested in the EU‐project EUROHARP only MONERIS claims to be capable of modelling nitrogen and phosphorus emissions in a landscape with mountainous slope. Results derived in the present study indicate that the MONERIS 2.14 model in its current version is not able to reproduce the measured nutrient loads in rivers from alpine catchments in Austria with a size of 70 to 400 km2. Despite this apparent limitation, MONERIS delivers a framework flexible enough to offer the possibility for the introduction of adaptations to regions that had not been a focus during its development. Significant improvements in model performance have been achieved during this study with relatively simple adaptations: (i) calibration a snowmelt constants, (ii) adaptation of the nitrogen balance for open and naturally covered areas, (iii) adaptation of the denitrification approach for groundwater of solid rock areas with low nitrogen surplus and high amount of leakage water, (iv) introduction of the differentiation of area‐specific suspended solids emission factors for mountainous open areas covered either with glaciers or not, (v) definition of new input parameters for phosphorus concentrations in solid limestone and schist/gneiss rocks and of dissolved phosphorus concentrations in surface runoff and groundwater flow for mountainous areas. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
998.
Mayuko Sato Yuko Mogi Toshikazu Nishikawa Shinichi Miyamura Tamotsu Nagumo Shigeyuki Kawano 《Planta》2009,229(4):781-791
The cyanelles of glaucocystophytes are probably the most primitive of known extant plastids and the closest to cyanobacteria.
Their kidney shape and FtsZ arc during the early stage of division define cyanelle division. In order to deepen and expand
earlier results (Planta 227:177–187, 2007), cells of Cyanophora paradoxa were fixed with two different chemical and two different freeze-fixation methods. In addition, cyanelles from C. paradoxa were isolated to observe the surface structure of dividing cyanelles using field emission scanning electron microscopy (FE-SEM).
A shallow furrow started on one side of the division plane. The furrow subsequently extended, covering the entire division
circle, and then invaginated deeply, becoming clearly visible. The typical FtsZ arc was 2.3–3.4 μm long. This length matches
that of the cleavage furrow observed using FE-SEM. The cyanelle cleavage furrows are from one-fourth to one-half of the circumference
of the division plane. The shallow furrow that appears on the cyanelle outer surface effectively changes the division plane.
Using freeze-fixation methods, the electron-dense stroma and peptidoglycan could be distinguished. In addition, an electron-dense
belt structure (the cyanelle ring) was observed inside the leading edge at the cyanelle division plane. The FtsZ arc is located
at the division plane ahead of the cyanelle ring. Immunogold-TEM localization shows that FtsZ is located interiorly of the
cyanelle ring. The lack of an outer PD ring, together with the arch-shaped furrow, suggests that the mechanical force of the
initial (arch shaped) septum furrow constriction comes from inside the cyanelle. 相似文献
999.
Min Wang Jarrett Mickens Mingzhang Gao Kathy D. Miller George W. Sledge Gary D. Hutchins Qi-Huang Zheng 《Steroids》2009,74(12):896-905
Aromatase and steroid sulfatase (STS) are particularly attractive targets in the treatment of estrogen-receptor-positive breast cancer and the development of enzyme-based cancer imaging agents for the biomedical imaging technique positron emission tomography (PET). New carbon-11-labeled sulfamate derivatives were first designed and synthesized as potential PET dual aromatase–steroid sulfatase inhibitor (DASSI) radiotracers for imaging of aromatase and STS expression in breast cancer. The target tracers 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8a) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8b) were prepared from their corresponding precursors 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (16) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (21) with [11C]CH3OTf under basic conditions through the O-[11C]methylation and isolated by the reversed-phase high pressure liquid chromatography (HPLC) method in 30–45% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The specific activity at end of synthesis (EOS) was 111–185 GBq/μmol. 相似文献
1000.
O. S. Fedorova O. F. Kuznetsova S. V. Shatik M. A. Stepanova Yu. N. Belokon V. I. Maleev R. N. Krasikova 《Russian Journal of Bioorganic Chemistry》2009,35(3):306-314
Tyrosine derivatives labeled with a short-lived fluorine-18 isotope (T 1/2 110 min), namely 2-[18F]fluoro-L-tyrosine (FTYR) and O-(2′-[18F]fluoroethyl)-L-tyrosine (FET), promising radiopharmaceuticals (RPs) for positron emission tomography (PET), were obtained by asymmetric syntheses. Accumulation of FTYR and FET in the rat tumor “Glioma 35 rats tumor” and in abscesses induced in Wistar rats muscles was studied and compared with that of a well-known glycolysis radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (FDG). It was shown that the relative accumulation indices of amino acid RPs were considerably lower than those of FDG. At the same time, tumor/muscle ratios were high enough (2.9 for FET and 3.9 for FTYR 120 min after injection) for reliable tumor visualization. The data obtained indicated a possibility in principle to use FTYR and FET for differentiated PET diagnostics of brain tumors and inflammation lesions. Of the tyrosine derivatives studied, FET seems to be the most promising agent due to a simple and easily automated method of preparation based on direct nucleophilic substitution of the leaving tosyloxy group of an enantiomerically pure Ni-(S)-BPS-(S)-Tyr(CH2CH2OTs) precursor by an activated [18F]fluoride. 相似文献