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981.
X Wang A Flynn AJ Waskiewicz BL Webb RG Vries IA Baines JA Cooper CG Proud 《Canadian Metallurgical Quarterly》1998,273(16):9373-9377
Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions. 相似文献
982.
AJ McNeil 《Canadian Metallurgical Quarterly》1997,16(22):2555-2572
We develop Bayesian methods for calculating shrinkage estimates of immunological progression rates (for example, CD4 count decline rates) in populations of HIV-infected patients. These methods make the assumption that decline of immunological markers may be modelled as approximately linear on some suitable chosen scale. They are applicable in situations where seroconversion times are unknown and follow-up of patients is variable, with some patients having only sparse measurements of immunological markers. Fitting of models is achieved by Gibbs sampling and CD4 count data from 603 members of the Edinburgh City Hospital Cohort with at least two CD4 determinations are analysed to provide an illustration. It is found that Bayesian shrinkage estimates for CD4 slopes on the square root scale are much more effective predictors of future CD4 counts than the least squares estimates, with respect to squared error loss. Of various shrinkage estimators considered, the most effective corresponds to the simplest model, which can also be fitted using SAS. A characterization of the pattern of CD4 loss in the Edinburgh cohort is obtained (mean rate of decline on root scale-1.61 per annum, standard deviation 1.03) and the effect of various covariates (sex, age, risk category and HLA antigen type) on immunological progression is considered. It is found that homosexual men in Edinburgh and patients with HLA haplotype A1B8DR3 experience significantly faster loss of CD4. 相似文献
983.
984.
AA Nanji L Miao P Thomas A Rahemtulla S Khwaja S Zhao D Peters SR Tahan AJ Dannenberg 《Canadian Metallurgical Quarterly》1997,112(3):943-951
BACKGROUND & AIMS: Inflammatory stimuli and lipid peroxidation up-regulate cyclooxygenase (COX)-2. This study evaluated the relationship between inflammatory mediators, COX expression, and pathological changes in experimental alcoholic liver disease. METHODS: Rats (5 per group) were fed ethanol and a diet containing saturated fat, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In the first set of experiments, whole livers were analyzed. In the second set of experiments, Kupffer cells, endothelial cells, and hepatocytes were isolated from rats in each group. Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed. RESULTS: Increased expression of COX-2 mRNA was detected in the livers of rats showing necroinflammatory changes. The Kupffer cell was the cell primarily responsible for the increase in COX-2 mRNA level. Increased expression of COX-2 was associated with increased levels of endotoxin, TNF-alpha mRNA, lipid peroxidation, and synthesis of thromboxane. COX-1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury. CONCLUSIONS: Up-regulation of COX-2 in alcoholic liver injury occurred in the presence of proinflammatory stimuli and resulted in increased synthesis of inflammatory and vasoactive eicosanoids. Down-regulation of COX-1 may result in decreased synthesis of cytoprotective eicosanoids and additionally exacerbate liver injury. 相似文献
985.
DP Felsenfeld MA Hynes KM Skoler AJ Furley TM Jessell 《Canadian Metallurgical Quarterly》1994,12(3):675-690
Subsets of axons in the embryonic nervous system transiently express the glycoprotein TAG-1, a member of the subfamily of immunoglobulin (Ig)-like proteins that contain both C2 class Ig and fibronectin type III domains. TAG-1 is attached to the cell surface by a glycosylphosphatidylinositol linkage and is secreted by neurons. In vitro studies have shown that substrate-bound TAG-1 promotes neurite outgrowth. We have examined the nature of axonal receptors that mediate the neurite-outgrowth promoting properties of TAG-1. Although TAG-1 can mediate homophilic binding, neurite outgrowth on a substrate of TAG-1 does not depend on the presence of TAG-1 on the axonal surface. Instead, neurite outgrowth on TAG-1 is inhibited by polyclonal antibodies directed against L1 and, independently, by polyclonal and monoclonal antibodies against beta 1-containing integrins. These results provide evidence that TAG-1 can interact with cell surfaces in both a homophilic and heterophilic manner and suggest that neurite extension on TAG-1 requires the function of both integrins and an L1-like molecule. 相似文献
986.
D Tan MR Cernadas P Aragoncillo MA Castilla MV Alvarez Arroyo AJ López Farré S Casado C Caramelo 《Canadian Metallurgical Quarterly》1998,13(3):594-601
BACKGROUND: The impaired renal function and vasodilatation that accompany age need to be re-addressed based upon the new knowledge concerning vascular nitric oxide (NO)-dependent systems. The present study examined the effects of age on the NO-related renal response. METHODS: The study was performed in euvolaemic, conscious Wistar rats, aged 5 and 18 months. Renal function and haemodynamic measurements with fluorescent microspheres were employed to assess differences between groups. RESULTS: A first set of experiments showed that ageing rats had a reduced natriuretic and diuretic response to acetylcholine, whereas the response to sodium nitroprusside was preserved. In the same regard, a reduction of the renal functional effects of L-arginine (L-Arg) and L-glycine (L-Gly) was found in the older rats. In the ageing rats, these responses were accompanied by an enhanced effect of the L-Arg competitive analogue, NwNLA, which provoked a marked reduction of renal function. This effect of NwNLA was blocked by the simultaneous administration of a small dose of L-Arg in the ageing but not in the young rats. Systemic haemodynamic studies revealed that in ageing rats, NwNLA reduced renal blood flow and increased renal vascular resistances in a significantly higher proportion than in younger animals. However, flow to other organs, namely, brain, spleen or liver, was affected in a similar manner in both young and old rats. Ultrastructural alterations were found in endothelial cells, which might constitute the anatomical basis for the observed functional derangements. CONCLUSIONS: The present experiments reveal that ageing is accompanied by significant differences in NO-related responses in the kidney which do not appear to affect blood flow to other organs. The response to L-Arg and L-Arg competitive analogues supports the existence of a marked dependency on NO-related mechanisms in the ageing rats, but not of a decreased baseline activity of the NO-dependent pathways. 相似文献
987.
Algorithm based on simulated annealing for land-use allocation 总被引:1,自引:0,他引:1
Inés Santé-Riveira Marcos Boullón-Magán Rafael Crecente-Maseda David Miranda-Barrós 《Computers & Geosciences》2008,34(3):259-268
This article describes the use of simulated annealing for allocation of land units to a set of possible uses on, the basis of their suitability for those uses, and the compactness of the total areas allotted to the same use or kind of use, which are fixed a priori. The results obtained for the Terra Chá district of Galicia (N.W. Spain) using different objective weighting schemes are compared with each other and with those obtained for this district under the same area constraints, using hierarchical optimization, ideal point analysis, and multi-objective land allocation (MOLA) to maximize average use suitability. Inclusion of compactness in the simulated annealing objective function avoids the highly disperse allocations typical of optimizations that ignore this sub-objective. 相似文献
988.
By homology to the mgt gene (encoding a macrolide glycosyltransferase) from Streptomyces lividans, a 3.3-kb DNA fragment from the oleandomycin producer, Streptomyces antibioticus, was cloned and sequenced. Analysis of the sequence revealed the presence of the 3' end of a gene (ORF1) and two complete ORFs (ORF2 and oleD), all of them translationally coupled. The deduced product of the sequenced region of ORF1 contained the typical signature of integral membrane proteins responsible for the translocation of substrates across the membrane. The ORF2 product did not show significant similarity with proteins in databases, but contains an N-terminus leader peptide region characteristic of secreted proteins, and a lipid attachment site motif characteristic of membrane lipoproteins synthesized with a precursor signal peptide. The oleD product showed clear similarity with several UDP-glucuronosyl- and UDP-glycosyl-transferases from different origins and particularly with the mgt gene from S. lividans, and might encode a glycosyltransferase activity capable of inactivating macrolides. It is proposed that these three genes could participate in the intracellular glycosylation of oleandomycin and its secretion during antibiotic production. 相似文献
989.
JN BeMiller MC Birchenall Sparks TW Fong AJ Pappelis 《Canadian Metallurgical Quarterly》1976,5(6):419-426
In stalk parenchyma tissue of WF9 X 38-11 single corn (Zea mays L.), there was a per cell increase in RNA synthesis and a slight increase in total RNA as cells became older. In cob parenchyma tissue of WF9 X 38-11 single cross corn, both total RNA content and RNA synthesis per cell decreased with the age of cells. In first developed leaf tissue of FR43 X FR14A single cross corn, RNA synthesis increased steadily but only slightly over its life span. The pattern of RNA synthesis and destruction in senescing leaf tissue of seedlings and two sources of parenchyma tissue of maturing plants appeared to differ. 相似文献
990.
SI Tazuke NM Mazure J Sugawara G Carland GH Faessen LF Suen JC Irwin DR Powell AJ Giaccia LC Giudice 《Canadian Metallurgical Quarterly》1998,95(17):10188-10193
IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability. 相似文献