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951.
Arginine vasopressin enhances pHi regulation in the presence of HCO3- by stimulating three acid-base transport systems 总被引:14,自引:0,他引:14
Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi increase is a necessary signal for mitogenesis. In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts. In mesangial cells, arginine vasopressin (AVP) raises pHi in the absence of HCO3-, but lowers it when HCO3- is present; growth is stimulated under both conditions. We report here that, in the presence of HCO3-, AVP stimulates two potent HCO3- transporters, as well as the Na+/H+ exchanger. These are the Na+-dependent and Na+-independent Cl-/HCO3- exchangers. Our results indicate that AVP causes acidification in the presence of HCO3- because, at the resting pHi, it stimulates Na+-independent Cl-/HCO3- exchange (which lowers pHi) more than it stimulates the sum of Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange (both of which raise pHi). The stimulation of three acid-base transporters by the growth factor AVP greatly enhances the ability of the cell to regulate pHi. 相似文献
952.
Putative transcription activator with alternative isoforms encoded by human ZFX gene 总被引:9,自引:0,他引:9
A Schneider-G?dicke P Beer-Romero L G Brown G Mardon S W Luoh D C Page 《Nature》1989,342(6250):708-711
953.
Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum 总被引:52,自引:0,他引:52
The primary event in the pathogenesis of severe malaria in Plasmodium falciparum infection is thought to be adherence of trophozoite- and schizont-infected erythrocytes to capillary endothelium, a process called sequestration. Identifying the endothelial molecules used as receptors is an essential step in understanding this disease process. Recent work implicates the membrane glycoprotein CD36 (platelet glycoprotein IV; refs 2-5) and the multi-functional glycoprotein thrombospondin as receptors. Although CD36 has a widespread distribution on microvascular endothelium, it may not be expressed on all capillary beds where sequestration occurs, especially in the brain. The role of thrombospondin in cell adhesion, in vitro or in vivo, is less certain. We have noticed that some parasites bind to human umbilical-vein endothelial cells independently of CD36 or thrombospondin. To screen for alternative receptors, we have developed a novel cell-adhesion assay using transfected COS cells, which confirms that CD36 is a cell-adhesion receptor. In addition, we find that an endothelial-binding line of P. falciparum binds to COS cells transfected with a complementary DNA encoding intercellular adhesion molecule-1. As this molecule is widely distributed on capillaries and is inducible, this finding may be relevant to the pathogenesis of severe malaria. 相似文献
954.
T-cell receptor delta-chain can substitute for alpha to form a beta delta heterodimer 总被引:11,自引:0,他引:11
Specific monoclonal antibodies have made possible the identification of two T-cell antigen receptor (TCR) heterodimers, alpha beta TCR and gamma delta TCR. Formation of these receptors is largely separated by the preferential pairing of alpha-TCR with beta and gamma-TCR with delta, the sequential rearrangement and expression of the TCR loci during thymic development and the deletion of the delta-loci either prior to or concomitant with alpha-rearrangement in alpha beta TCR cells. Here we show that delta-TCR can substitute for alpha in pairing with beta to form a beta delta heterodimer. This receptor is expressed on the cell surface of the T-leukaemia cell line DND41 as analysed with beta- and delta-specific monoclonal antibodies. We suggest that a variety of factors including, for example, the deletion of the delta-TCR loci, can now be understood as exclusion mechanisms operating to prevent not only the formation of gamma delta receptors, but also of beta delta T-cell receptors, thereby promoting the numerically dominant alpha beta TCR lineage. Nevertheless, some developing T-cells that do not rearrange the alpha-loci may express the beta delta TCR as described here. 相似文献
955.
956.
The Drosophila posterior-group gene nanos functions by repressing hunchback activity 总被引:11,自引:0,他引:11
The development of the body plan in the Drosophila embryo depends on the activity of maternal determinants localized at the anterior and posterior of the egg. These activities define both the polarity of the anterior-posterior (AP) axis and the spatial domains of expression of the zygotic gap genes, which in turn control the subsequent steps in segmentation. The nature and mode of action of one anterior determinant, the bicoid(bcd) gene product, has recently been defined, but the posterior determinants are less well characterized. At least seven maternally acting genes are required for posterior development. Mutations in these maternal posterior-group genes result in embryos lacking all abdominal segments. Cytoplasmic transplantation studies indicate that the maternally encoded product of the nanos(nos) gene may act as an abdominal determinant, whereas the other maternal posterior-group genes appear to be required for the appropriate localization and stabilization of this signal. Here we show that the lack of the nos gene product can be compensated for by eliminating the maternal activity of the gap gene hunchback (hb). Embryos lacking both of these maternally derived gene products are viable and can survive as fertile adults. These results suggest that the nos gene product functions by repressing the activity of the maternal hb products in the posterior of the egg. 相似文献
957.
Vesicular removal by oligodendrocytes of membrane attack complexes formed by activated complement 总被引:15,自引:0,他引:15
N J Scolding B P Morgan W A Houston C Linington A K Campbell D A Compston 《Nature》1989,339(6226):620-622
Oligodendrocytes synthesize myelin in the central nervous system and maintain it in lamellar sheaths around axons. Techniques for studying oligodendrocyte development in vitro can be used, indirectly, to investigate the myelin injury that occurs in human and experimental demyelinating disease. Cell-mediated immune mechanisms are necessary but not sufficient to induce myelin damage in vivo; more recently complement has also been implicated in the pathogenesis both of multiple sclerosis and experimental allergic encephalomyelitis. Previously we have demonstrated that antibody-independent complement activation occurs in vitro at the oligodendrocyte surface. Here we show that the ensuing oligodendrocyte injury is reversible, and that recovery involves the release of membrane-attack complex-enriched vesicles from the surface of viable cells. The demonstration of morphologically and immunochemically identical vesicles in the cerebrospinal fluid of patients with multiple sclerosis suggests that reversible complement-mediated injury contributes to myelin damage in vivo. 相似文献
958.
A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin 总被引:23,自引:0,他引:23
V K Chaudhary C Queen R P Junghans T A Waldmann D J FitzGerald I Pastan 《Nature》1989,339(6223):394-397
Antibodies and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Escherichia coli by attaching the light and heavy chain variable domains together with a peptide linker. Here we describe the construction and expression in E. coli of a single chain antibody toxin fusion protein, anti-Tac(Fv)-PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)-PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells. 相似文献
959.
960.
Mutant Drosophila embryos in which all cells adopt a neural fate 总被引:6,自引:0,他引:6
In the Drosophila embryo, early developmental decisions lead to all cells adopting one of several initial fates, such as those characteristic of the germ layers. The central nervous system is formed subsequently from the neurogenic region of the ectoderm, in which progenitor cells of the neuroblasts and ventral epidermis are intermingled. Two classes of genes govern the segregation of neuroblasts and peripheral sensory organs. The pro-neural class of genes, for example, the achaete-scute complex, participates in the initial decision to make each uniquely positioned neuroblast or sensory organ, but are initially expressed in groups of cells. The segregation of a neuroblast or sensory organ from an equivalent group of equipotential cells involves a mechanism of lateral inhibition whereby the future epidermal cells are prevented from engaging in the primary dominant neural fate. In the absence of this inhibitory signal, all cells of the group will become neural by default. The neurogenic class of genes is thought to mediate these cell interactions. Here we report that cells in embryos mutant for shaggy which are unable to adopt any of the early initial fates, instead develop neural characteristics. 相似文献