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911.
Rapid switching to multiple antigenic and adhesive phenotypes in malaria.   总被引:67,自引:0,他引:67  
Adhesion of parasitized erythrocytes to post-capillary venular endothelium or uninfected red cells is strongly implicated in the pathogenesis of severe Plasmodium falciparum malaria. Neoantigens at the infected red-cell surface adhere to a variety of host receptors, demonstrate serological diversity in field isolates and may also be a target of the host-protective immune response. Here we use sequential cloning of P. falciparum by micromanipulation to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity.  相似文献   
912.
J Laurence  A S Hodtsev  D N Posnett 《Nature》1992,358(6383):255-259
In the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4+ T cells (approximately 1%) infected with the human immunodeficiency virus (HIV) are randomly targeted or not. Here we present evidence that human CD4 T-cell lines expressing selected T-cell antigen receptor V beta gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, V beta 12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24gag antigen) than V beta 6.7a lines. This is consistent with a superantigen effect, because the V beta selectivity was observed with several divergent HIV-1 isolates, was dependent on antigen-presenting cells and on major histocompatibility complex (MHC) class II but was not MHC class II-restricted. The in vivo significance of these findings is supported by the preferential stimulation of V beta 12+ T cells by freshly obtained irradiated antigen-presenting cells from some HIV-1-seropositive but not HIV-1-negative donors. Moreover, cells from patients positive for viral antigen (gp120) were enriched in the V beta 12 subpopulation. V beta 12+ T cells were not deleted in AIDS patients, however, raising the possibility that a variety of mechanisms contribute to T-cell depletion. Our results indicate that a superantigen targets a subpopulation of CD4+ cells for viral replication.  相似文献   
913.
A M O'Rourke  M F Mescher 《Nature》1992,358(6383):253-255
In addition to the antigen-specific T-cell receptor (TCR), T cells bear an array of 'accessory' molecules that can contribute to stable adhesion to the antigen-bearing cell and provide costimulatory signals. For several of these, T-cell adhesion to the ligand can be activated by TCR-dependent signalling (a signal from the TCR primes the coreceptor to bind to its ligand). It is unclear whether the individual coreceptors share common mechanisms of priming and cosignalling, and perhaps act in a redundant manner, or whether they act in a distinct way and contribute uniquely to the activation process. We report here the use of isolated alloantigen, class I proteins and fibronectin ligands to show that coreceptors on cytotoxic T lymphocytes are activated sequentially and deliver distinct biochemical signals on binding to their ligands. TCR engagement activates CD8 by a protein tyrosine kinase-dependent pathway, and CD8 then acts as a signal for initiation of polyphosphoinositide hydrolysis on binding to class I. In contrast, activated adhesion to fibronectin does not initiate polyphosphoinositide hydrolysis, but amplifies hydrolysis once it has been initiated. Thus, cytotoxic T-lymphocyte activation involves a TCR-initiated cascade of adhesion and signalling events leading to response.  相似文献   
914.
Human infection by genetically diverse SIVSM-related HIV-2 in west Africa.   总被引:41,自引:0,他引:41  
Our understanding of the biology and origins of human immunodeficiency virus type 2 (HIV-2) derives from studies of cultured isolates from urban populations experiencing epidemic infection and disease. To test the hypothesis that such isolates might represent only a subset of a larger, genetically more diverse group of viruses, we used nested polymerase chain reactions to characterize HIV-2 sequences in uncultured mononuclear blood cells of two healthy Liberian agricultural workers, from whom virus isolation was repeatedly unsuccessful, and from a culture-positive symptomatic urban dweller. Analysis of pol, env and long terminal repeat regions revealed the presence of three highly divergent HIV-2 strains, one of which (from one of the healthy subjects) was significantly more closely related to simian immunodeficiency viruses infecting sooty mangabeys and rhesus macaques (SIVSM/SIVMAC) than to any virus of human derivation. This subject also harboured multiply defective viral genotypes that resulted from hypermutation of G to A bases. Our results indicate that HIV-2, SIVSM and SIVMAC comprise a single, highly diverse group of lentiviruses which cannot be separated into distinct phylogenetic lineages according to species of origin.  相似文献   
915.
P K Sorger  A W Murray 《Nature》1992,355(6358):365-368
In somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosine 15 (Y15) of p34cdc2, the protein kinase subunit of maturation promoting factor, accelerate the entry into mitosis and abolish the ability of unreplicated DNA to arrest cells in G2. Because the tyrosine phosphorylation of p34cdc2 is conserved in S. pombe, Xenopus, chicken and human cells, the regulation of p34cdc2-Y15 phosphorylation could be a universal mechanism mediating the S-phase feedback control and regulating the initiation of mitosis. We have investigated these phenomena in the budding yeast Saccharomyces cerevisiae. We report here that the CDC28 gene product (the S. cerevisiae homologue of cdc2) is phosphorylated on the equivalent tyrosine (Y19) during S phase but that mutations that prevent tyrosine phosphorylation do not lead to premature mitosis and do not abolish feedback controls. We have therefore demonstrated a mechanism that does not involve tyrosine phosphorylation of p34 by which cells arrest their division in response to the presence of unreplicated or damaged DNA. We speculate that this mechanism may not involve the inactivation of p34 catalytic activity.  相似文献   
916.
Ehrlich carcinoma and EL-4 thymoma ascites cells were subjected in vitro to heat shock, ATP depletion, oxidative stress, Ca2+ overlading and iodoacetamide treatment. After the transient stresses, Triton (X-100)-insoluble TIS) fractions were isolated from the cells and analysed by electrophoresis and immunoblotting. All stresses used caused rapid aggregation of cell proteins. This was manifested in a signficant rise in protein content in the TIS fractions. The protein increase was mostly due to and increase in the insolubility of actin, 57 kDa protein of intermediate filaments, 70 kDa heat shock protein (HSP 70), and some specific proteins whose insolubilization was a characteristic sign for each type of cell injury. Different survival rates in the cell lines after either stress corrlated well with differences in their TIS protein accretion. Possible mechanisms for stress-induced protein aggregation and its relationship with cell viability are suggested.  相似文献   
917.
Genetic variation has been found in males of aD. simulans population for their eagerness to hybridize withD. melanogaster females. In a search for traits involved in this hybridization, males ofD. simulans were tested for mating speed and sexual vigour. Between-male differences were detected in both sexual traits, but no relationship was noticed between them, nor with the frequency of hybridization. Thus male mating propensities appear to be unrelated to the breakdown of sexual isolation between these sibling species.  相似文献   
918.
The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.  相似文献   
919.
The objective of this paper is to establish reliable prediction equations relating cotton fibreproperties measured by HVI system and yarn quality,A useful statistical method is adopted for de-veloping a multiple regression model interpreting the relation between the data of Spinlab HVIfibre properties and quality parameters of yarn STQ (Strength Tex Quotient).The percent relativecontribution of a fibre property with respect of STQ is also assessed.The results show that the totalcontribution of the HVI measured fibre properties can account for 77.4% of known variation ofyarn STQ.The main feature of the approach is its flexibility in accommodating all fibre properties.The examination of regression equation showed that it could be well applied to predict STQ ofyarns spun from the same spinning system,but,for different spinning systems and also for yarns ofdifferent linear density,modification of the equation would be needed.  相似文献   
920.
原油中的水滴在高压直流电场中被电场力分散成小液滴。通过测定小液滴的平均粒径和原油中被分散的水量,发现水滴的电分散程度与温度和电场强度的变化有密切关系。温度改变原油性质来影响水滴的变形断裂,其中粘性阻力起主导作用。电场强度会明显影响水滴所受的电场力。在80℃下,场强1500V/cm时有10%以上的水滴被分散,到场强5 000V/cm时则达到40%以上。场强超过7 000V/cm以后分散作用的增强逐步减弱。  相似文献   
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