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Odlo K Hentzen J dit Chabert JF Ducki S Gani OA Sylte I Skrede M Flørenes VA Hansen TV 《Bioorganic & medicinal chemistry》2008,16(9):4829-4838
A series of cis-restricted 1,5-disubstituted 1,2,3-triazole analogues of combretastatin A-4 (1) have been prepared. The triazole 12f, 2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)aniline, displayed potent cytotoxic activity against several cancer cell lines with IC50 values in the nanomolar range. The ability of triazoles to inhibit tubulin polymerization has been evaluated, and 12f inhibited tubulin polymerization with IC50 = 4.8 μM. Molecular modeling experiments involving 12f and the colchicine binding site of ,β-tubulin showed that the triazole moiety interacts with β-tubulin via hydrogen bonding with several amino acids. 相似文献
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For the extrinsic hand flexors (flexor digitorum profundus, FDP; flexor digitorum superficialis, FDS; flexor pollicis longus, FPL), moment arm corresponds to the tendon's distance from the center of the metacarpalphalangeal (MP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joint. The clinical value of establishing accurate moment arms has been highlighted for biomechanical modeling, the development of robotic hands, designing rehabilitation protocols, and repairing flexor tendon pulleys (Brand et al., 1975; An et al., 1983; Thompson and Giurintano, 1989; Deshpande et al., 2010; Wu et al., 2010). In this study, we define the moment arms for all of the extrinsic flexor tendons of the hand across all digital joints for all digits in cadaveric hands. 相似文献
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Anna Pelet Agnès Rotig Catherine Bonaïti-Pellié Daniel Rabier Valérie Cormier Elias Toumas Danièle Hentzen Jean-Marie Saudubray Arnold Munnich 《Human genetics》1990,84(2):167-171
Summary Ornithine transcarbamylase (OTC) deficiency is an X-linked disease responsible for lethal neonatal hyperammonemia in males. Partial OTC deficiency also occurs in females and can be responsible for life-threatening hyperammonemic comas in heterozygotes (15%). Increased orotic acid excretion occurs in both symptomatic and asymptomatic carriers, especially under protein loading tests. The disease is therefore partially dominant with neonatal lethality in the hemizygous male; the fraction of new mutations has previously been estimated to be low in males (point estimation = 0, upper bound of the confidence interval = 0.16) and 57% in females. Genetic counseling in this disease is difficult because it is not clear whether a negative protein loading test rules out carrier status. In an attempt to determine how reliable the test is for carrier detection, we investigated ten obligate carriers for orotic acid excretion; considering all data available, we concluded that the test is rarely negative in obligate carriers (8%). Consequently, a negative test in a mother decreases the minimum risk of being a carrier from 84% a priori to 30% if she had an affected son and from 43% a priori to 5% if she had a heterozygous daughter. Finally, the diagnosis of a new mutation in the germ cells of the maternal grandfather in one particular family could be ascertained by extensive DNA analysis. 相似文献
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Chakraborty A Hentzen ER Seo SM Smith CW 《American journal of physiology. Cell physiology》2003,284(1):C103-C110
Granulocyte colony stimulating factor(G-CSF) is well known for its ability to drive the maturation andmobilization of neutrophils. G-CSF also appears to have the potentialto activate functions of mature neutrophils, influencing recruitment atsites of inflammation and tissue injury. We investigated the ability ofG-CSF to stimulate adhesion of isolated blood neutrophils. G-CSFinduced significant adherence to intercellular adhesion molecule(ICAM)-1 that was both macrophage antigen-1 (Mac-1) and leukocytefunction-associated antigen-1 dependent. The kinetics ofG-CSF-stimulated adhesion to ICAM-1 peaked at 11 min without detectablesurface upregulation of Mac-1. This was in marked contrast tochemokines, in which peak activation of adhesion is seen within 1 minof stimulation. In contrast to chemokine-induced adhesion, G-CSFstimulation was not inhibited by pertussis toxin. G-CSF also augmentedthe attachment of neutrophils to activated human umbilical veinendothelial cells (HUVEC) through specific effects on neutrophils,because HUVEC appear to lack functional G-CSF receptors. 相似文献
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