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71.
72.
The failure of DMSO to alter the permeability of the blood-brain barrier has been studied using several polar, nonpolar, hydrophilic, and hydrophobic compounds labeled with selected radioactive isotopes. The metabolites were Na131I, 131I-iodinated human serum albumin, l-[35S]methionine, dl-[ring-2-14C]tryptophan, [U-14C]sucrose, d-[6-14C]glucose, and [4-14C]cholesterol. DMSO was injected intraperitoneally at a dose of 1 g/kg followed after 1 hr by the intracarotid injection of the labeled metabolite. An appropriate volume of saline was substituted for the DMSO in control animals. The brain and one gastrocnemius muscle were removed at selected intervals up to 30 min and the uptake into these tissues was measured.It was found that the permeability of neither the blood-brain barrier nor skeletal muscle was altered by this concentration of DMSO. This dose of DMSO, administered intravenously, frequently caused death and, intraperitoneally, caused muscular twitching, lethargy, and hematuria. 相似文献
73.
Searle F Gac-Breton S Keane R Dimitrijevic S Brocchini S Sausville EA Duncan R 《Bioconjugate chemistry》2001,12(5):711-718
Ellipticine derivatives have potential as anticancer drugs. Their clinical use has been limited, however, by poor solubility and host toxicity. As N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anticancer conjugates are showing promise in early clinical trials, a series of novel HPMA copolymer conjugates have been prepared containing the 6-(3-aminopropyl)-ellipticine derivative (APE, NSC176328). Drug was linked to the polymer via GFLG or GG peptide side chains. To optimize biological behavior, HPMA copolymer-GFLG-APE conjugates with different drug loading (total APE: 2.3-7% w/w; free APE: <0.1% w/w) were synthesized. Conjugation of APE to HPMA copolymers considerably increased its aqueous solubility (>10-fold). HPMA copolymer-GG-APE did not liberate drug in the presence of isolated lysosomal enzymes (tritosomes), but HPMA copolymer-GFLG-APE released APE to a maximum of 60% after 5 h. The rate of drug release was influenced by drug loading; lower loading led to greater release. Whereas free APE (35 microg/mL) caused significant hemolysis (50% after 1 h), HPMA copolymer-APE conjugates were not hemolytic up to 300 microg/mL (APE-equiv). As would be expected from its cellular pharmacokinetics, HPMA copolymer-GFLG-APE was >75 times less cytotoxic than free drug (IC(50) approximately 0.4 microg/mL) against B16F10 melanoma in vitro. However, in vivo when tested in mice bearing s.c. B16F10 melanoma, HPMA copolymer-GFLG-APE (1-10 mg/kg single dose, APE-equiv) given i.p. was somewhat more active (highest T/C value of 143%) than free APE (1 mg/kg) (T/C =127%). HPMA copolymer-APE conjugates warrant further evaluation as potential anticancer agents. 相似文献
74.
Dandelions (Taraxacum officinale Weber(sensu lato); Asteraceae) have been introduced to NorthandSouth America with human migration from Europe. While potential sourcepopulations have both sexually and obligate asexually (agamospermous)reproducing lineages, apparently only the latter have successfully colonizedtheAmericas. The consequences of obligate agamospermy on dandelion populationgenetic diversity in North America remain little explored. Here we use fourdifferent synthetic DNA probes that reveal genetic markers at multiplevariable-number-tandem-repeat (VNTR) loci to examine patterns of geneticvariation among plants collected along three different central North Americantransects with plants (21 to 22 individuals per transect) separated by: 1) >2 m and < 60 m (short transect); 2) > 5km and < 30 km (medium transect); and 3) > 30km and < 340 km (long transect). The mean numberofVNTR markers revealed per plant was 59.3. Co-clonal individuals (proportion ofbands shared exceeding 90%) were found in each transect, with the indexof clonality (the percent of co-clonal individuals detected in a transect)ranging from 34.12% for the short transect to 18.65% for the longtransect. Co-clonal individuals were separated by up to 200 km.With redundant examples of co-clonal individuals removed, mean similarity(proportion of band sharing) of distinct genotypes within transects was 0.426,and no statistical differences in level of similarity between transects, norindication of genetic differentiation between transects, was detected (meanFst between transect levels with all individuals included =0.05). These results indicate: 1) that dandelion genetic diversity ofcolonizinglineages in central North America is moderately high and does not reflectextreme bottleneck effects shown by some colonizing species; and 2) thatdandelion seed dispersal can be very effective in maintaining similar levels ofgenetic diversity at the different scales of sampling in this study, withcertain clones maintaining numerous, widespread individuals. Evidence that VNTRmutation is detectable within dandelion clonal lineages is presented,demonstrating that clonal families with lines increasinglydifferentiated from one another will continually evolve, and that Muller'srachet is, in all likelihood, turning for asexual lines. 相似文献
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76.
Whiteaker JR Zhang H Eng JK Fang R Piening BD Feng LC Lorentzen TD Schoenherr RM Keane JF Holzman T Fitzgibbon M Lin C Zhang H Cooke K Liu T Camp DG Anderson L Watts J Smith RD McIntosh MW Paulovich AG 《Journal of proteome research》2007,6(2):828-836
Multiple approaches for simplifying the serum proteome have been described. These techniques are generally developed across different laboratories, samples, mass spectrometry platforms, and analysis tools. Hence, comparing the available schemes is impossible from the existing literature because of confounding variables. We describe a head-to-head comparison of several serum fractionation schemes, including N-linked glycopeptide enrichment, cysteinyl-peptide enrichment, magnetic bead separation (C3, C8, and WCX), size fractionation, protein A/G depletion, and immunoaffinity column depletion of abundant serum proteins. Each technique was compared to results obtained from unfractionated human serum. The results show immunoaffinity subtraction is the most effective means for simplifying the serum proteome while maintaining reasonable sample throughput. The reported dataset is publicly available and provides a standard against which emergent technologies can be compared and evaluated for their contribution to serum-based biomarker discovery. 相似文献
77.
Recent discoveries of single-gene influences on social behaviour have generated a great deal of interest in the proximate mechanisms underlying the expression of complex behaviours. Length polymorphism in a microsatellite in the regulatory region of the gene encoding the vasopressin 1a receptor (avpr1a) has been associated with both inter- and intra-specific variation in socially monogamous behaviour in voles (genus Microtus) under laboratory conditions. Here, we evaluate the relationship between avpr1a length polymorphism and social associations, genetic monogamy, and reproductive success in free-living prairie vole (M. ochrogaster) populations. We found no evidence of a relationship between avpr1a microsatellite length and any of our correlates of either social or genetic monogamy in the field. Our results, especially when taken in conjunction with those of recent experimental studies in semi-natural enclosures, suggest that avpr1a polymorphism is unlikely to have been a major influence in the evolution or maintenance of social monogamy in prairie voles under natural conditions. 相似文献
78.
79.
Abstract Palladium catalyzed carboxyamidation at the 8-position of 8-bromoadenosine and 8-bromoguanosine nucleosides is a versatile reaction, which allows primary, secondary, heterocyclic, aromatic mine and amino acids to be incorporated into purine nucleosides. 相似文献
80.
Dongfeng Gu Jiang He Pamela G. Coxson Petra W. Rasmussen Chen Huang Anusorn Thanataveerat Keane Y. Tzong Juyang Xiong Miao Wang Dong Zhao Lee Goldman Andrew E. Moran 《PLoS medicine》2015,12(8)