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51.
HL-60 cells undergo terminal differentiation and apoptosis in response to different types of sub-toxic and toxic perturbations respectively. The mechanism by which cells sense different amounts of perturbation to activate pathways that lead to the engagement of a relevant biological response is not known. The response of HL-60 cells to treatment with the immunosuppressant mycophenolic acid (MPA), a specific inhibitor of dGTP/GTP-synthesis, allowed quantitation of a metabolic perturbation which triggered a cellular response. 1.5 microM MPA induced 38% terminal differentiation to CD14 positive, early monocyte-like cells and 22% cell death by apoptosis, whereas 3 microM MPA induced 70% apoptosis but no differentiation. Despite the difference in biological outcomes, 72 h exposure to both 1.5 microM and 3 microM MPA caused a similar ( approximately 75%) depletion of total GTP levels. Cells synchronized by centrifugal elutriation were treated with MPA. Elutriated cells were overall less sensitive to the effects of MPA but 3 microM MPA induced significantly less apoptosis and more differentiation in an elutriation-enriched G1-population than in a population normally distributed in the cell cycle, suggesting that the effects of MPA in S-phase may subsequently lead to cell death. However, analysis of apoptosis by using a terminal deoxynucleotidyltransferase assay and measurement of bromodeoxyuridine incorporation showed that apoptosis was engaged in G1. Analysis of the phosphorylation status of the retinoblastoma protein demonstrated that Rb was hypophosphorylated prior to apoptosis and that in apoptotic cells, separated by flow cytometry, Rb protein was absent, presumably due to proteolysis. The loss of Rb protein did not appear to permit transit to S-phase, and was not accompanied by an expression of c-Myc. Surprisingly, therefore, an antimetabolite inducing a loss of GTP brought about cell death by apoptosis in the G1 phase of the cell cycle. 相似文献
52.
The structure of the glycopeptides of a human M-immunoglobulin 总被引:9,自引:0,他引:9
S Hickman R Kornfeld C K Osterland S Kornfeld 《The Journal of biological chemistry》1972,247(7):2156-2163
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The role of sialic acid in determining the survival of glycoproteins in the circulation 总被引:58,自引:0,他引:58
A G Morell G Gregoriadis I H Scheinberg J Hickman G Ashwell 《The Journal of biological chemistry》1971,246(5):1461-1467
55.
In connection with the estimation of the average fecundability of a group of women, it has been assumed in the past that the waiting time for a conception follows a type I geometric distribution, and its two parameters have been estimated by the method of moments and the method of maximum likelihood. In a follow-up study, starting with a group of women, there is always the possibility that some women will remain nonpregnant in the limited period of time they are observed, and the problem arises as to how to estimate the same parameters if the follow-up experiment is terminated after a fixed period of time. The present paper deals with this truncation problem, and provides three different methods for estimating the parameters, which are applied to data from the Menstrual and Reproductive History Study at the University of Minnesota. In the last section, an extended model is presented which incorporates the possibility of dropout cases. 相似文献
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DALDINIA CONCENTRICA ATTACKING THE WOOD OF FRAXINUS EXCELSIOR 总被引:1,自引:0,他引:1
57.
Nampally Sreenivasachary Heiko Kroth Pascal Benderitter Anne Hamel Yvan Varisco David T. Hickman Wolfgang Froestl Andrea Pfeifer Andreas Muhs 《Bioorganic & medicinal chemistry letters》2017,27(6):1405-1411
The aggregation of amyloid-β peptides into cytotoxic oligomeric and fibrillary aggregates is believed to be one of the major pathological events in Alzheimer disease. Here we report the design and synthesis of a novel series of indole and 7-azaindole derivatives containing, nitrile, piperidine and N-methyl-piperidine substituents at the 3-position to prevent the pathological self-assembly of amyloid-β. We have further demonstrated that substitution of the azaindole and indole derivatives at the 3 positions is required to obtain compounds with improved physicochemical properties to allow brain penetration. 相似文献
58.
Liu J Rumsey JW Das M Molnar P Gregory C Riedel L Hickman JJ 《In vitro cellular & developmental biology. Animal》2008,44(5-6):162-168
We are attempting to recreate a stretch reflex circuit on a patterned Bio-MEMS (bio-microelectromechanical systems) chip with deflecting micro-cantilevers. The first steps to recreate this system is to be able to grow individual components of the circuit (sensory neuron, motoneuron, skeletal muscle, and muscle spindle) on a patternable, synthetic substrate coating the MEMS device. Sensory neurons represent the afferent portion of the stretch reflex arc and also play a significant role in transmitting the signal from the muscle spindle to the spinal cord motoneurons. We have utilized a synthetic silane substrate N-1[3-(trimethoxysilyl) propyl) diethylenetriamine (DETA) on which to grow and pattern the cells. DETA forms a self-assembled monolayer on a variety of silicon substrates, including glass, and can be patterned using photolithography. In this paper, we have evaluated the growth of sensory neurons on this synthetic silane substrate. We have investigated the immunocytochemical and electrophysiological properties of the sensory neurons on DETA and compared the resultant properties with a biological control substrate (ornithine/laminin). Immunocytochemical studies revealed the survival and growth of all three subtypes of sensory neurons: trkA, trkB, and trkC on both surfaces. Furthermore, whole-cell patch clamp recordings were used to study the electrophysiological properties of the sensory neurons on the two surfaces. There were no significant differences in the electrical properties of the neurons grown on either surface. This is the first study analyzing the immunocytochemical and electrophysiological properties of sensory neurons grown long-term in a completely defined environment and on a nonbiological substrate. 相似文献
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