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991.
Pharmacokinetic and biodistribution study following systemic administration of Fospeg® – a Pegylated liposomal mTHPC formulation in a murine model 下载免费PDF全文
Haiyan Xie Pontus Svenmarker Johan Axelsson Susanna Gräfe Maria Kyriazi Niels Bendsoe Stefan Andersson‐Engels Katarina Svanberg 《Journal of biophotonics》2015,8(1-2):142-152
Fospeg® is a newly developed photosensitizer formulation based on meso‐tetra(hydroxyphenyl)chlorin (mTHPC), with hydrophilic liposomes to carry the hydrophobic photosensitizer to the target tissue. In this study the pharmacokinetics and biodistribution of Fospeg® were investigated by high performance liquid chromatography at various times (0.5–18 hours) following systemic i.v. administration. As a model an experimental HT29 colon tumor in NMRI nu/nu mice was employed. Our study indicates a higher plasma peak concentration, a longer circulation time and a better tumor‐to‐skin ratio than those of Foslip®, another liposomal mTHPC formulation. Data from ex vivo tissue fluorescence and reflectance imaging exhibit good correlation with chemical extraction. Our results have shown that optical imaging provides the potential for fluorophore quantification in biological tissues. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim) 相似文献
992.
Zhen Tao Noa Rosental Baruch I. Kanner Armanda Gameiro Juddy Mwaura Christof Grewer 《The Journal of biological chemistry》2010,285(23):17725-17733
The glutamate transporter excitatory amino acid carrier 1 (EAAC1) catalyzes the co-transport of three Na+ ions, one H+ ion, and one glutamate molecule into the cell, in exchange for one K+ ion. Na+ binding to the glutamate-free form of the transporter generates a high affinity binding site for glutamate and is thus required for transport. Moreover, sodium binding to the transporters induces a basal anion conductance, which is further activated by glutamate. Here, we used the [Na+] dependence of this conductance as a read-out of Na+ binding to the substrate-free transporter to study the impact of a highly conserved amino acid residue, Thr101, in transmembrane domain 3. The apparent affinity of substrate-free EAAC1 for Na+ was dramatically decreased by the T101A but not by the T101S mutation. Interestingly, in further contrast to EAAC1WT, in the T101A mutant this [Na+] dependence was biphasic. This behavior can be explained by assuming that the binding of two Na+ ions prior to glutamate binding is required to generate a high affinity substrate binding site. In contrast to the dramatic effect of the T101A mutation on Na+ binding, other properties of the transporter, such as its ability to transport glutamate, were impaired but not eliminated. Our results are consistent with the existence of a cation binding site deeply buried in the membrane and involving interactions with the side chain oxygens of Thr101 and Asp367. A theoretical valence screening approach confirms that the predicted site of cation interaction has the potential to be a novel, so far undetected sodium binding site. 相似文献
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H Hendrix T Lindhout K Mertens W Engels H C Hemker 《The Journal of biological chemistry》1983,258(6):3637-3644
The activation of human prothrombin by the bacterial protein staphylocoagulase proceeds via the formation of a very stable equimolar complex. Unmasking of the active center in the prothrombin moiety of the complex is not caused by limited proteolysis. The kinetics of activation of human prothrombin by staphylocoagulase has been studied. The second order rate constant at pH 7.5, 37 degrees C, is 3.3 X 10(6) M-1 S-1. This reaction rate is close to reported diffusion-controlled rates of protein-protein interaction. The dissociation constant of the complex was too low to be measurable. From the kinetic data it is assumed that the first order rate constant for dissociation is orders of magnitude less than 10(-5) S-1. However, dissociation of the complex did occur in the presence of sodium dodecyl sulfate. Equimolar amounts of staphylocoagulase protect human thrombin, but not human factor Xa and bovine thrombin, against inactivation by antithrombin III. From these findings we postulate that tertiary structural changes in the thrombin region of prothrombin caused by a highly specific interaction between staphylocoagulase and that region unmask the active site. 相似文献
996.
Importance of Cycling and Recycling of Mineral Nutrients within Plants for Growth and Development 总被引:2,自引:0,他引:2
Cycling of mineral nutrients, i.e. retranslocation in the phloem from the shoot to the roots, and recycling, i.e. translocation of cycled nutrients back in the xylem to the shoot can contribute substantially to the fluxes of phloem-mobile nutrients between roots and shoot. Cycling and recycling of nutrients serves several well defined functions. These include supplying the root with nutrients assimilated in the shoot (nitrate and sulphate reduction), maintenance of cation-anion balance, providing additional driving force for solute flow in the xylem and phloem, and acting as a shoot signal to convey nutrient demand to the roots. Cycling of mineral nutrients like K is also required to cover the demand for growth of apical root zones and to smooth out fluctuations that occur spatially and with time in the external nutient supply of soil-grown plants. Cycling and recycling of mineral nutrients is also closely related to the process of phloem loading and export of photosynthates from source leaves. This is particularly true for potassium, magnesium and phosphorus. Nutrient deficiency-induced shifts in dry matter partitioning between shoot and roots are therefore closely related to the solute flow in the phloem not only of photosynthates but also mineral nutrients from source leaves to roots. More research is needed, however, to elucidate in greater detail the contribution of cycling and recycling of mineral nutrients in the integration of growth processes at the whole plant level. 相似文献
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998.
Y. Wang W. Friedl Christof Lamberti Corina Ruelfs Roland Kruse Peter Propping 《Human genetics》1997,100(3-4):362-364
Evaluation of the causative role of germline mutations in DNA mismatch repair genes in hereditary nonpolyposis colorectal
cancer (HNPCC) families can be difficult. Whereas nonsense, frameshift or splice-site mutations are presumed to lead to dysfunctional
gene products and thus are generally considered to be causative, the evaluation of missense mutations often remains uncertain.
We observed a novel germline mutation in the hMLH1 gene (His→Pro at codon 329) in an HNPCC family. The same missense mutation
also occurred as a somatic event in the colonic tumours of two other HNPCC patients who had germline mutations at different
sites of the hMLH1gene. Thus, the H329P mutation present in the germline can be considered as having an aetiological role
in this HNPCC family.
Received: 1 April 1997 / Accepted: 13 May 1997 相似文献
999.
Stem segments of the maize (Zea mavs L.) hybrids LGH, Eta Ipho (EI) and a brown midrib mutant. INRA 260 bm3 (bm3) were freeze-dried, ground and analysed for cell wall content, hemicellulose, cellulose, lignin and in vitro cell wall degradability with rumen fluid. Stem cross-sections, stained with acid phloroglucinol (AP) and chlorine sulphite (CS) showed an increased intensity in staining during maturation, but no considerable difference in staining intensity was observed between genotypes. The lignin content increased during maturation with evidently less lignin in bm3 than in EI and LGH. However, cell wall degradability did not differ between the older stem segments of EI and bm3, although the amount of lignin in LGH was twice that of bm3.
It can be concluded that an increase in lignin content occurs simultancously with a decrease in cell wall degradability within a genotype. However, between different genotypes the lignin content is not an indicator of degree of cell wall degradability. 相似文献
1000.
Abstract By the phosphitetriester approach we synthesized the fragments for constructing a synthetically idealized promoter (SIP). The total construction consists of the promoter, operator and Shine-Dalgarno (SD) region. This control region was fused to the gene for γ-interferon. We chemically synthesized a control region in order to optimally express our synthetic genes considering the following criteria. For easy modifications, e.g. for structure function studies we designed each functional domain as a cassette which can conveniently be dissected by the appropriate restriction enzymes. The regulation unit consists of a promoter1,2, an operator3 and a Shine-Dalgarno-sequence4 (FIG. 1). 相似文献