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61.
Zechel C Backfisch G Delzer J Geneste H Graef C Hornberger W Kling A Lange UE Lauterbach A Seitz W Subkowski T 《Bioorganic & medicinal chemistry letters》2003,13(2):165-169
Solid-phase synthesis and SAR of alpha(V)beta(3)-receptor antagonists based on a N(1)-substituted 4-amino-1H-pyrimidin-2-one scaffold are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta(3) in the nano- to subnanomolar range and high selectivity versus related integrins like alpha(IIb)beta(3). For selected examples efficacy in functional cellular assays was demonstrated. 相似文献
62.
The thermoacidophilic archaeon Acidianus ambivalens contains a monomeric 47 kDa type-II NADH dehydrogenase (NDH), which contains a covalently bound flavin. In this work, by a combination of several methods, namely (31)P-nuclear magnetic resonance and fluorescence spectroscopies, it is proven that this enzyme contains covalent FMN, a novelty among this family of enzymes, which were so far thought to mainly have the flavin dinucleotide form. Discrimination between several possible covalent flavin linkages was achieved by spectral and fluorescence experiments, which identified an 8alpha-N(1)-histidylflavin-type of linkage. Analysis of the gene-deduced amino acid sequence of type-II NDH showed no transmembranar helices and allowed the definition of putative dinucleotide and quinone binding motifs. Further, it is suggested that membrane anchoring can be achieved via amphipatic helices. 相似文献
63.
Hartl A Weiss R Hochreiter R Scheiblhofer S Thalhamer J 《Methods (San Diego, Calif.)》2004,32(3):328-339
In the past 10 years, a great number of studies have demonstrated that injection of plasmid DNA coding for certain genes results in the induction of humoral and cellular immune responses against the respective gene product. This vaccination approach covers a broad range of possible applications, including the induction of protective immunity against viral, bacterial, and parasitic infections, and it opens new perspectives for treatment of cancer. Surprisingly, DNA immunization also turned out as a promising novel type of immunotherapy against allergy. In this paper, we describe the construction of DNA vaccines for application in allergy models. Beyond, we offer a palette of recently developed modulations to optimize DNA vaccines for allergy treatment by increasing their immunogenicity and minimizing their anaphylactic potential. 相似文献
64.
Gouze JN Gouze E Palmer GD Liew VS Pascher A Betz OB Thornhill TS Evans CH Grodzinsky AJ Ghivizzani SC 《Arthritis research & therapy》2003,5(5):R301-R309
Anakinra, the recombinant form of IL-1 receptor antagonist (IL-1Ra), has been approved for clinical use in the treatment of
rheumatoid arthritis as the drug Kineret™, but it must be administered daily by subcutaneous injection. Gene transfer may
offer a more effective means of delivery. In this study, using prostaglandin E2 production as a measure of stimulation, we quantitatively compared the ability of anakinra, as well as that of IL-1Ra delivered
by gene transfer, to inhibit the biologic actions of IL-1β. Human synovial fibroblast cultures were incubated with a range
of doses of anakinra or HIG-82 cells genetically modified to constitutively express IL-1Ra. The cultures were then challenged
with recombinant human IL-1β either simultaneously with addition of the source of IL-1Ra or 24 hours later. In a similar manner,
the potencies of the two sources of IL-1Ra were compared when human synovial fibroblasts were challenged with IL-1β produced
constitutively by genetically modified cells. No significant difference in inhibitory activity was observed between recombinant
protein and IL-1Ra provided by the genetically modified cells, under static culture conditions, even following incubation
for 4 days. However, under culture conditions that provided progressive dilution of the culture media, striking differences
between these methods of protein delivery became readily apparent. Constitutive synthesis of IL-1Ra by the genetically modified
cells provided sustained or increased protection from IL-1 stimulation over time, whereas the recombinant protein became progressively
less effective. This was particularly evident under conditions of continuous IL-1β synthesis. 相似文献
65.
Background
Ovulatory menstrual cycles are essential for women’s fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory.Methods
This is a single-cycle, cross-sectional, population-based study—a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20–49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL).Results
Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001).Conclusion
Anovulation in a random population occurs in over a third of clinically normal menstrual cycles. 相似文献66.
67.
Henninger N Woderer S Kloetzer HM Staib A Gillen R Li L Yu X Gretz N Kraenzlin B Pill J 《Biosensors & bioelectronics》2007,23(1):26-34
Considerable progress in improved control of disturbed glucose metabolism can be expected by continuous glucose monitoring. The aim of the study was to evaluate in male Sprague-Dawley rats tissue response to implantation of a new amperometric glucose-oxidase-based glucose sensor (NTS) compared to a commercially available sensor system CGMS of MiniMed. Both sensors were tested under working conditions over a period of 3 days. Using NTS, glucose in interstitial fluid reflected glucose in arterial blood even in rapidly changing hyper- and hypoglycaemia whereas the CGMS did not detect the experimentally induced glucose changes adequately. Gene expression profiling was performed using Affymetrix chips. Acute phase response to injury by sensor application for a short time is indicated by down regulation of the increase in mRNA of proteases e.g. metallothionein-1alpha and matrix metalloprotease-3 at day 3. Improvement of anabolic situation is suggested by decrease in mRNA of insulin-like growth factor binding protein whereas increase of heme oxygenase and hypoxia-inducible factor may be related to defense mechanisms. Changes of mRNA together with slight fibrous capsule formation suggest good histocompatibility. Comparability of the patterns of changed mRNA in tissue surrounding SCGM with and without operating voltage as shown in dendrogram indicates no contribution of hydrogen peroxide to worsening biocompatibility. Beside established histological investigations of foreign body reaction weeks or months after implantation, gene expression profiling provides additional information to biocompatibility already early after implantation. 相似文献
68.
Tungsten in biological systems 总被引:9,自引:0,他引:9
69.
Diversity of resistance to leaf rust caused by Puccinia triticina can be enhanced in wheat (Triticum aestivum) cultivars through a better knowledge of resistance genes that are present in important cultivars and germplasm. Multi-pathotype tests on 84 wheat cultivars grown in Denmark, Finland, Norway and Sweden during 1992-2002 and 39 differential testers enabled the postulation of nine known genes for seedling resistance to leaf rust. Genes Lr1, Lr2a, Lr3, Lr10, Lr13, Lr14a, Lr17, Lr23 and Lr26 were found singly or in combination in 47 of the cultivars (55.9%). The most frequently occurring genes in cultivars grown in Sweden were Lr13 (20.4%), Lr14a (14.8%) and Lr26 (14.8%). Lr14a was the most common gene in cultivars grown in Norway (18.7%), Lr13 in Denmark (35.5%) and Lr10 in Finland (20.0%). Although 28 cultivars (33.3%) exhibited a response pattern that could not be assigned to resistance genes or combinations present in the tester lines, several pathotypes carried virulence and hence these genes or combinations are of limited use. Nine cultivars (10.7%) lacked detectable seedling resistance. One cultivar was resistant to all pathotypes used in the study. 相似文献
70.