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261.
Radiolabeled somatostatin analogues have been successfully used for targeted radiotherapy and for imaging of somatostatin receptor (sst1-5)-positive tumors. Nevertheless, these analogues are subject to improving their tumor-to-nontarget ratio to enhance their diagnostic or therapeutic properties, preventing nephrotoxicity. In order to understand the influence of lipophilicity and charge on the pharmacokinetic profile of [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)]-somatostatin-based radioligands such as [DOTA,1-Nal3]-octreotide (DOTA-NOC), different spacers (X) based on 8-amino-3,6-dioxaoctanoic acid (PEG2), 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG4), N-acetyl glucosamine (GlcNAc), triglycine, beta-alanine, aspartic acid, and lysine were introduced between the chelator DOTA and the peptide NOC. All DOTA-X-NOC conjugates were synthesized by Fmoc solid-phase synthesis. The partition coefficient (log D) at pH = 7.4 indicated that higher hydrophilicity than [111In-DOTA]-NOC was achieved with the introduction of the mentioned spacers, except with triglycine and beta-alanine. The high affinity of [InIII-DOTA]-NOC for human sst2 (hsst2) was preserved with the structural modifications, while an overall drop for hsst3 affinity was observed, except in the case of [InIII-DOTA]-beta-Ala-NOC. The new conjugates preserved the good affinity for hsst5, except for [InIII-DOTA]-Asn(GlcNAc)-NOC, which showed decreased affinity. A significant 1.2-fold improvement in the specific internalization rate in AR4-2J rat pancreatic tumor cells (sst2 receptor expression) at 4 h was achieved with the introduction of Asp as a spacer in the parent compound. In sst3-expressing HEK cells, the specific internalization rate at 4 h for [111In-DOTA]-NOC (13.1% +/- 0.3%) was maintained with [111In-DOTA]-beta-Ala-NOC (14.0% +/- 1.8%), but the remaining derivatives showed <2% specific internalization. Biodistribution studies were performed with Lewis rats bearing the AR4-2J rat pancreatic tumor. In comparison to [111In-DOTA]-NOC (2.96% +/- 0.48% IA/g), the specific uptake in the tumor at 4 h p.i. was significantly improved for the 111In-labeled sugar analogue (4.17% +/- 0.46% IA/g), which among all the new derivatives presented the best tumor-to-kidney ratio (1.9). 相似文献
262.
The concept of photoprotection by dietary means is gaining momentum. Plant constituents such as carotenoids and flavonoids
are involved in protection against excess light in plants and contribute to the prevention of UV damage in humans. As micronutrients,
they are ingested with the diet and are distributed into light-exposed tissues, such as skin or the eye where they provide
systemic photoprotection. β-Carotene and lycopene prevent UV-induced erythema formation. Likewise, dietary flavanols exhibit
photoprotection. After about 10–12 weeks of dietary intervention, a decrease in the sensitivity toward UV-induced erythema
was observed in volunteers. Dietary micronutrients may contribute to life-long protection against harmful UV radiation. 相似文献
263.
Herr I Gassler N Friess H Büchler MW 《Apoptosis : an international journal on programmed cell death》2007,12(2):271-291
More than a quarter of a century ago, the phenomenon of glucocorticoid-induced apoptosis in the majority of hematological
cells was first recognized. More recently, glucocorticoid-induced antiapoptotic signaling associated with apoptosis resistance
has been identified in cells of epithelial origin, most of malignant solid tumors and some other tissues. Despite these huge
amount of data demonstrating differential pro- and anti-apoptotic effects of glucocortioids, the underlying mechanisms of
cell type specific glucocorticoid signaling are just beginning to be described. This review summarizes our present understanding
of cell type-specific pro- and anti-apoptotic signaling induced by glucocorticoids. In the first section we give a summary
and update of known glucocorticoid-induced pathways mediating apoptosis in hematological cells. We shortly introduce mechanisms
of glucocorticoid resistance of hematological cells. We highlight and discuss the emerging molecular evidence of a general
induction of survival signaling in epithelial cells and carcinoma cells by glucocorticoids. We provide a model for glucocorticoid-induced
resistance in cells growing in a tissue formation. Thus, attachment to the extracellular matrix and cell-cell contacts typical
for e.g. epithelial and tumor cells may be crucially involved in switching the balance of several interacting pathways to
survival upon treatment with glucocorticoids. 相似文献
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265.
Fröhlich J Koustiane C Kämpfer P Rosselló-Mora R Valens M Berchtold M Kuhnigk T Hertel H Maheshwari DK König H 《Systematic and applied microbiology》2007,30(1):68-74
Wood-eating termites feed on a diet highly deficient in nitrogen. They must complement their diet with the aid of nitrogen-fixing bacteria. Nitrogen fixation in the gut has been demonstrated, but information about nitrogen-fixing bacteria in pure culture is scarce. From the higher termite Nasutitermes nigriceps the symbiotic bacterial strain M3A was isolated, which thrives in the hindgut contents. The Gram-negative strain exhibited similarities to the species of the genus Ensifer (including Sinorhizobium) on the basis of morphological and physiological/biochemical features. The 16S rRNA gene analysis showed the highest sequence similarity of the isolate M3A to Ensifer adhaerens (>99%; ATCC 33499). The DNA-DNA hybridization revealed a similarity of 66% with E. adhaerens (NCIMB12342(T)). In contrast to the type strain the isolate M3A possesses the capacity to nodulate plant roots. This is the first report on the detailed identification of a rhizobia-related strain from the intestinal tract of animals. Strain M3A has been deposited with two culture collections (DSM10169; ATCC BAA-396). 相似文献
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269.
Integral and associated lysosomal membrane proteins 总被引:2,自引:0,他引:2
Schröder B Wrocklage C Pan C Jäger R Kösters B Schäfer H Elsässer HP Mann M Hasilik A 《Traffic (Copenhagen, Denmark)》2007,8(12):1676-1686
We searched for novel proteins in lysosomal membranes, tentatively participating in molecular transport across the membrane and/or in interactions with other compartments. In membranes purified from placental lysosomes, we identified 58 proteins, known to reside at least partially in the lysosomal membrane. These included 17 polypeptides comprising or associated with the vacuolar adenosine triphosphatase. We report on additional 86 proteins that were significantly enriched in the lysosomal membrane fraction. Among these, 12 novel proteins of unknown functions were found. Three were orthologues of rat proteins that have been identified in tritosomes by Bagshaw RD et al. (A proteomic analysis of lysosomal integral membrane proteins reveals the diverse composition of the organelle. Mol Cell Proteomics 2005;4:133-143). Here, the proteins encoded by LOC201931 (FLJ38482) and LOC51622 (C7orf28A) were expressed with an appended fluorescent tag in HeLa cells and found to be present in lysosomal organelles. Among the lysosomally enriched proteins, also 16 enzymes and transporters were detected that had not been assigned to lysosomal membranes previously. Finally, our results identified a particular set of proteins with known functions in signaling and targeting to be at least partially associated with lysosomes. 相似文献
270.
Markus Wagner Ansgar Kahmen Helmut Schlumprecht Volker Audorff Jörg Perner Nina Buchmann Wolfgang W. Weisser 《应用植被学》2007,10(1):15-24
Question: How useful are Ellenberg N‐values for predicting the herbage yield of Central European grasslands in comparison to approaches based on ordination scores of plant species composition or on soil parameters? Location: Central Germany (11°00′‐11°37’E, 50°21‐50°34’N, 500–840 m a.s.l.). Methods: Based on data from a field survey in 2001, the following models were constructed for predicting herbage yield in montane Central European grasslands: (1) Linear regression of mean Ellenberg N‐, R‐ and F‐values; (2) Linear regression of ordination scores derived from Non‐metric Multidimensional Scaling (NMDS) of vegetation data; and (3) Multiple linear regression (MLR) of soil variables. Models were evaluated by cross‐validation and validation with additional data collected in 2002. Results: Best predictions were obtained with models based on species composition. Ellenberg N‐values and NMDS scores performed equally well and better than models based on Ellenberg R‐ or F‐values. Predictions based on soil variables were least accurate. When tested with data from 2002, models based on Ellenberg N‐values or on NMDS scores accurately predicted productivity rank order of sites, but not the actual herbage yield of particular sites. Conclusions: Mean Ellenberg N‐values, which are easy to calculate, are as accurate as ordination scores in predicting herbage yield from plant species composition. In contrast, models based on soil variables may be useful for generating hypotheses about the factors limiting herbage yield, but not for prediction. We support the view that Ellenberg N‐values should be called productivity values rather than nitrogen values. 相似文献