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151.
Study of erythrocyte sedimentation behavior by piezoelectric crystal impedance sensor 总被引:6,自引:0,他引:6
Based on the impedance characteristic of erythrocytes at high frequency, the response of piezoelectric crystal impedance (PCI) sensor in the erythrocyte suspension was derived and verified experimentally. A method of using PCI sensor to investigate erythrocyte aggregation-sedimentation phenomenon was proposed. From the frequency response of the PCI sensor, the erythrocyte aggregation time and sedimentation rate could be obtained during erythrocyte aggregation and sedimentation. With the present method, the effects of the erythrocyte deformability, the osmotic pressure and the coexisting macromolecules on the erythrocyte sedimentation rate were studied. The results show that the PCI sensor possesses some advantages, such as good sensitivity, simplicity of use and no thermal effect for the impedance study of erythrocyte aggregation and sedimentation. 相似文献
152.
Reduced bone formation is the main finding in glucocorticoid-induced osteoporosis. The aim of this study was to determine whether differentiation of cultured human osteoblasts is inhibited by high concentrations of hydrocortisone. We measured the levels of mRNAs for three markers of cellular differentiation, type 1 collagen (COL1), alkaline phosphatase (ALP), and osteocalcin (OC), in four lines of human osteoblasts from female donors cultured with doses of hydrocortisone from 0 microM to 4 microM. The change in ALP/COL1 mRNA ratio over a given time was used to determine the average rate of differentiation of the cells in a culture. Although basal expression profiles and their changes with time were different for the different cell lines, all cell lines showed a dose-dependent rise in the rate of increase of ALP mRNA relative to COL1 mRNA. However, increase in OC mRNA with time, seen here only in young donor hOBs, was significantly inhibited by 4 microM hydrocortisone, indicating that hydrocortisone can inhibit OC expression while promoting cellular differentiation. The data suggest that increasing concentrations of glucocorticoid, including concentrations similar to plasma levels in patients receiving oral glucocorticoid therapy, increase the rate of cellular differentiation. 相似文献
153.
Byth KF Cooper N Culshaw JD Heaton DW Oakes SE Minshull CA Norman RA Pauptit RA Tucker JA Breed J Pannifer A Rowsell S Stanway JJ Valentine AL Thomas AP 《Bioorganic & medicinal chemistry letters》2004,14(9):2249-2252
Modification of imidazo[1,2-a]pyridine CDK inhibitors lead to identification of less lipophilic imidazo[1,2-b]pyridazine series of CDK inhibitors. Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs significantly. Protein inhibitor structure determination has confirmed differences in binding mode and given some understanding of these differences in SAR. Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice. 相似文献
154.
155.
Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment 总被引:12,自引:0,他引:12
Zhang SQ Yang W Kontaridis MI Bivona TG Wen G Araki T Luo J Thompson JA Schraven BL Philips MR Neel BG 《Molecular cell》2004,13(3):341-355
The protein-tyrosine phosphatase Shp2 plays an essential role in growth factor and integrin signaling, and Shp2 mutations cause developmental defects and/or malignancy. Previous work has placed Shp2 upstream of Ras. However, the mechanism of Shp2 action and its substrate(s) are poorly defined. Additional Shp2 functions downstream of, or parallel to, Ras/Erk activation also are proposed. Here, we show that Shp2 promotes Src family kinase (SFK) activation by regulating the phosphorylation of the Csk regulator PAG/Cbp, thereby controlling Csk access to SFKs. In Shp2-deficient cells, SFK inhibitory C-terminal tyrosines are hyperphosphorylated, and the tyrosyl phosphorylation of multiple SFK substrates, including Plcgamma1, is decreased. Decreased Plcgamma1 phosphorylation leads to defective Ras activation on endomembranes, and may help account for impaired Erk activation in Shp2-deficient cells. Decreased phosphorylation/activation of other SFK substrates may explain additional consequences of Shp2 deficiency, including altered cell spreading, stress fibers, focal adhesions, and motility. 相似文献
156.
Experiments involving investigation of the neuroendocrine basis for paternal care in rodents risk activation of aggressive behavior toward pups. To minimize pain and suffering during tests of parental responsiveness requiring retrieval of a displaced pup to its nest, a method of anesthetizing the pup was developed in Djungarian hamsters, Phodopus campbelli. A surgical plane of anesthesia, as measured by criteria, such as respiratory depression, loss of the pedal reflex, and failure to increase respiratory rate or to vocalize in response to handling, was achieved by use of intraperitoneal administration of a combination of ketamine and xylazine. Both parents (tested separately) expressed normal behavior toward anesthetized pups. In random order, a saline-injected or anesthetized pup was displaced from its nest in the home cage. There were no differences in pick-up or retrieval rates between saline and anesthetized pups for either parent. A third test using an unmanipulated pup confirmed that parental behavior was not reduced toward an anesthetized pup. However, if anesthetized pups were tested first among littermates, retrieval by males was less likely. This method will, therefore, underestimate retrieval behavior in males, but not females. Adult male hamsters that had never been parents also expressed expected behavior by attacking the pup in 45% of cases. This method provides an efficient and effective means of protecting pups while allowing adults to express a wide range of parental and infanticidal behaviors. It also has application in behavioral screening of transgenic strains toward unrelated young. 相似文献
157.
Fang Y Park IH Wu AL Du G Huang P Frohman MA Walker SJ Brown HA Chen J 《Current biology : CB》2003,13(23):2037-2044
BACKGROUND: The mammalian target of rapamycin (mTOR) regulates cell growth and proliferation via the downstream targets ribosomal S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). We have identified phosphatidic acid (PA) as a mediator of mitogenic activation of mTOR signaling. In this study, we set out to test the hypotheses that phospholipase D 1 (PLD1) is an upstream regulator of mTOR and that the previously reported S6K1 activation by Cdc42 is mediated by PLD1. RESULTS: Overexpression of wild-type PLD1 increased S6K1 activity in serum-stimulated cells, whereas a catalytically inactive PLD1 exerted a dominant-negative effect on S6K1. More importantly, eliminating endogenous PLD1 by RNAi led to drastic inhibition of serum-stimulated S6K1 activation and 4E-BP1 hyperphosphorylation in both HEK293 and COS-7 cells. Knockdown of PLD1 also resulted in reduced cell size, suggesting a critical role for PLD1 in cell growth control. Using a rapamycin-resistant S6K1 mutant, Cdc42's action was demonstrated to be through the mTOR pathway. When Cdc42 was mutated in a region specifically required for PLD1 activation, its ability to activate S6K1 in the presence of serum was hindered. However, when exogenous PA was used as a stimulus, the PLD1-inactive Cdc42 mutant behaved similarly to the wild-type protein. CONCLUSIONS: Our observations reveal the involvement of PLD1 in mTOR signaling and cell size control, and provide a molecular mechanism for Cdc42 activation of S6K1. A new cascade is proposed to connect mitogenic signals to mTOR through Cdc42, PLD1, and PA. 相似文献
158.
McMullan R Lax S Robertson VH Radford DJ Broad S Watt FM Rowles A Croft DR Olson MF Hotchin NA 《Current biology : CB》2003,13(24):2185-2189
The epidermis comprises multiple layers of specialized epithelial cells called keratinocytes. As cells are lost from the outermost epidermal layers, they are replaced through terminal differentiation, in which keratinocytes of the basal layer cease proliferating, migrate upwards, and eventually reach the outermost cornified layers. Normal homeostasis of the epidermis requires that the balance between proliferation and differentiation be tightly regulated. The GTP binding protein RhoA plays a fundamental role in the regulation of the actin cytoskeleton and in the adhesion events that are critically important to normal tissue homeostasis. Two central mediators of the signals from RhoA are the ROCK serine/threonine kinases ROCK-I and ROCK-II. We have analyzed ROCK's role in the regulation of epidermal keratinocyte function by using a pharmacological inhibitor and expressing conditionally active or inactive forms of ROCK-II in primary human keratinocytes. We report that blocking ROCK function results in inhibition of keratinocyte terminal differentiation and an increase in cell proliferation. In contrast, activation of ROCK-II in keratinocytes results in cell cycle arrest and an increase in the expression of a number of genes associated with terminal differentiation. Thus, these results indicate that ROCK plays a critical role in regulating the balance between proliferation and differentiation in human keratinocytes. 相似文献
159.
Yang J Si T Ling Y Ruan Y Han Y Wang X Zhou M Zhang D Zhang H Kong Q Liu C Li X Yu Y Liu S Shu L Ma D Wei J Zhang D 《Life sciences》2003,72(26):3017-3021
An increasing amount of evidence suggests that the pathophysiology of schizophrenia is associated with the abnormal immune system, and cytokines may be important in schizophrenia. Among these cytokines, interleukin-1beta may play a role in the pathogenesis of the disease. In the present study, we investigated the genetic association between a TaqI polymorphism in interleukin-1beta gene (IL-1beta) and schizophrenia by restriction fragment length polymorphism (RFLP) analysis among 132 Chinese families of Han descent. The transmission disequilibrium test (TDT) did not demonstrate an allelic association with schizophrenia. Our results suggested that the TaqI polymorphism in IL-1beta gene might not confer increased susceptibility for schizophrenia. 相似文献
160.
Protein kinase C-dependent phosphorylation and mitochondrial translocation of aldose reductase 总被引:4,自引:0,他引:4
Varma T Liu SQ West M Thongboonkerd V Ruvolo PP May WS Bhatnagar A 《FEBS letters》2003,534(1-3):175-179
Although aldose reductase (AR) is a critical participant in osmoregulation, and the metabolism of glucose and aldehydes derived from lipid peroxidation, post-translational mechanisms regulating its activity have not been identified. In this paper, we report that stimulation of protein kinase C (PKC) in several cell types induces phosphorylation of AR and translocation of the phosphorylated protein to the mitochondria. In vitro, recombinant AR was directly phosphorylated by activated PKC, suggesting that AR may be an in vivo PKC substrate. Together, these observations reveal a novel link between PKC activation and the regulation of glucose and aldehyde metabolism. 相似文献