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Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.  相似文献   
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As an alternative to surgical splenectomy, partial splenic embolization was performed in seven children for hypersplenism manifested by splenomegaly, thrombocytopenia, leukopenia, and erythrocyte hemolysis. Within a few days, platelet and leukocyte counts rose significantly in all patients and were maintained in six of seven patients during a follow-up period of 9 to 69 months. Spleen size and abdominal distention also decreased significantly in all children. There were no infectious complications.  相似文献   
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This article is the second of two papers that review the field of spatially sensitive social scientific research into the links between social status and transport disadvantage. The first paper undertook a comprehensive review of the social scientific and transport planning literature to mark the level of development in the field and identify conceptual and methodological issues and constraints in this field of inquiry. The present article supports the advancement of socially and geographically sensitive transport research by opportunities for the development of more sophisticated spatial analytical methodologies. The approach we present is able to account for factors not previously addressed in either social or transport planning research, in particular the temporal dimensions of transport service accessibility. The article articulates the methodology through an empirical case study of socio-spatial transport disadvantage within the Gold Coast City. The article demonstrates that there are important theoretical and practical lessons to be gained for researchers and policy makers in addressing the social dimensions of transport and infrastructure provision. Further, the article argues that an attentiveness to new ways of combining and representing social and transport data-sets can promote policy relevant empirical social inquiry. The article also contributes in a productive way to the empirical knowledge of Australia's sixth-largest metropolitan area, which is often overlooked by urban scholars.  相似文献   
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The growth in beer of 15 brewery strains of Lactobacillus was detected using the automatic conductance measuring technique afforded by the Malthus 8 Growth Analyser. 0·15% ammonium chloride was added to the beer as an electrolyte and sodium acetate was used to raise the pH from ca 4·0 to 4·2 or above. No measurable responses were obtained using unmodified beer. The value of the method for development in routine brewery microbiological control is briefly discussed.  相似文献   
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