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81.
U Beyer T Roth P Schumacher G Maier A Unold AW Frahm HH Fiebig C Unger F Kratz 《Canadian Metallurgical Quarterly》1998,41(15):2701-2708
One strategy for improving the selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules or carrier proteins. Thus, five maleimide derivatives of chlorambucil were bound to thiolated human serum transferrin which differ in the stability of the chemical link between drug and spacer. The maleimide ester derivatives 1 and 2 were prepared by reacting 2-hydroxyethylmaleimide or 3-maleimidophenol with the carboxyl group of chlorambucil, and the carboxylic hydrazone derivatives 5-7 were obtained through reaction of 2-maleimidoacetaldehyde, 3-maleimidoacetophenone, or 3-maleimidobenzaldehyde with the carboxylic acid hydrazide derivative of chlorambucil. The alkylating activity of transferrin-bound chlorambucil was determined with the aid of 4-(4-nitrobenzyl)pyridine (NBP) demonstrating that on average 3 equivalents were protein-bound. Evaluation of the cytotoxicity of free chlorambucil and the respective transferrin conjugates in the MCF7 mammary carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence assay demonstrated that the conjugates in which chlorambucil was bound to transferrin through non-acid-sensitive linkers, i.e., an ester or benzaldehyde carboxylic hydrazone bond, were not, on the whole, as active as chlorambucil. In contrast, the two conjugates in which chlorambucil was bound to transferrin through acid-sensitive carboxylic hydrazone bonds were as active as or more active than chlorambucil in both cell lines. Especially, the conjugate in which chlorambucil was bound to transferrin through an acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were approximately 3-18-fold lower than those of chlorambucil. Preliminary toxicity studies in mice showed that this conjugate can be administered at higher doses in comparison to unbound chlorambucil. The structure-activity relationships of the transferrin conjugates are discussed with respect to their pH-dependent acid sensitivity, their serum stability, and their cytotoxicity. 相似文献
82.
Rosari Saleh Lusitra Munisa Wolfhard Beyer 《Solar Energy Materials & Solar Cells》2006,90(18-19):3449-3455
The microstructure of DC sputtered amorphous silicon carbon (a-SiC:H) is studied by effusion measurements of hydrogen and of implanted inert gases helium, neon, argon and secondary ion mass spectrometry. The results suggest that the motion of inert gas atoms is controlled by the diffusion, greatly depending on a broadening of network openings. Already at carbon concentrations of 25 at%, isolated voids disappeared presumably because interconnected voids are formed. A void formation is mainly attributed to an increase in hydrogen incorporation in the samples. 相似文献
83.
84.
S Stremetzne U Jaehde R Kasper J Beyer W Siegert W Schunack 《Canadian Metallurgical Quarterly》1997,33(6):978-979
A 13-year-old boy with a paratesticular embryonal rhabdomyosarcoma and a large thrombus into the inferior vena cava reaching the suprahepatic vein is presented. We used cardiopulmonary bypass with deep hypothermic circulatory arrest to realize a complete exeresis of the tumor and thrombus, followed by systemic chemotherapy and radiotherapy. Ten years later the patient is alive and doing well without any sequelae. 相似文献
85.
M Engelbach S Heerdt R G?rges T Kunt A Pfützner T Forst K Diefenbach S Walgenbach J Beyer 《Canadian Metallurgical Quarterly》1998,383(6):456-459
The role of susceptibility genes in the etiology of birth defects is unclear, but may involve in some cases multiple alleles at multiple loci. We suggest a simple epidemiologic approach to explore gene-gene interactions, and use it to reevaluate data from a recent case-control study on the possible association of neural tube defects (NTDs) with specific mutations of two genes, 5,10-methylene-tetrahydrofolate reductase (MTHFR) and cystathionine-beta synthase (CBS). We found that, compared with the common genotype, homozygosity for the MTHFR mutation alone was associated with a two-fold increased risk for NTDs, while homozygosity for the CBS mutation alone was not a risk factor. However, homozygous individuals for the mutations at both loci had a five-fold greater risk for NTDs than those with the reference genotype. Though the original study was too small to detect statistically significant differences among most of the risk estimates, these results, if confirmed by independent and larger studies, suggest that gene-gene interaction may play a role in modulating the susceptibility to NTDs in a proportion of affected individuals. This approach, moreover, could be a valuable adjunct to the study of gene gene interactions in the etiology of human disease. 相似文献
86.
Geesje Stoffels Hans-Georg Sahl gusta Gudmundsdttir 《International journal of food microbiology》1993,20(4):199-210
This paper describes a simple purification method for the purification of carnocin U149, a potential biopreservative produced by Carnobacterium piscicola U149. The protocol was also applicable for the isolation of nisin Z, which is a biopreservative produced by Lactococcus lactis SIK-83. The protocol consists of only two purification steps, XAD chromatography and cation exhange chromatography. It is quick, easy, and can be used for large scale purification of these lantibiotics. The bactericidal activity of carnocin U149 against carnobacteria, lactococci and Listeria was compared with that of nisin Z. The carnobacteria showed similar sensitivity towards carnocin U149 and nisin. The nisin producing L. lactis strains were very sensitive towards carnocin U149, while the non-producing L. lactis strains were more sensitive to nisin. The Listeria strains were weakly sensitive to carnocin U149, lower concentrations of nisin were needed to inhibit growth. 相似文献
87.
HM Hoffmeister S Szabo C Kastner ME Beyer U Helber S Kazmaier HP Wendel W Heller L Seipel 《Canadian Metallurgical Quarterly》1998,98(23):2527-2533
BACKGROUND: Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI. METHODS AND RESULTS: Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01). CONCLUSIONS: The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo. 相似文献
88.
Regarding micro components and systems, experimental work for characterizing materials’ properties as well as components’ and systems’ behaviors have to be supplemented by numerical analyses. These analyses should cover component and system issues. On a component level, macroscopic approaches are extended by methods allowing consideration of the influence of components’ grain structures including possible defects. On a system level, the high tolerances accepted for the individual components due to production inaccuracy and their effects on the expected load distribution capability of the system are taken into account. This paper presents approaches for simulation of micro components and systems using the finite element method and multi body simulation. Methods to overcome the abovementioned issues will be shown, as well as the effects of grain structure on the stress distribution in the individual components. 相似文献
89.
90.