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21.
Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high-resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high-grade VUR. 相似文献
22.
A V Cybulsky R J Quigg D J Salant 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(5):1511-1516
Using a model of rat membranous nephropathy (MN), we examined the relationship between the development of glomerular epithelial cell injury and the formation and stability of the membrane attack complex (MAC) of complement. Isolated rat kidneys were perfused with buffered bovine albumin (BSA) or various plasmas (complement source). Kidneys containing nephritogenic amounts of complement-fixing sheep antibody to glomerular epithelial antigens (aFx1A) perfused with BSA (n = 5), and normal kidneys perfused with normal human plasma in BSA (50% v/v, n = 6) excreted 0.30 +/- 0.02 mg protein/min/g during 90 min perfusion (control groups). When normal plasma was added to the perfusate of aFx1A kidneys at concentrations of 12.5, 25, and 50% v/v, protein excretion rose in a time- and concentration-dependent manner. Perfusions with 25% plasma resulted in baseline proteinuria from 0 to 20 min that increased to 2.8 +/- 0.9 mg/min/g at 20 to 40 min and 8.6 +/- 2.1 at 40 to 60 min (n = 4, p less than 0.01 vs control groups). Removal of plasma at 20 min did not prevent this rise in protein excretion (3.9 +/- 2.4 and 5.8 +/- 2.6 mg/min/g at 30 to 40 and 55 to 65 min respectively, p less than 0.01, n = 4). Perfusion of aFx1A kidneys with C8-deficient (C8D) human plasma (25% v/v, n = 4) or C6D rabbit serum (25% v/v, n = 2) independently produced low levels of proteinuria comparable with BSA, but in combination, the two reagents restored enhanced protein excretion (n = 2). In aFx1A kidneys containing C5b-7, addition of C8 and C9 (C6D serum) after intervals of 20, 60, or 90 min immediately reconstituted heavy proteinuria. Thus, the magnitude of MAC-induced glomerular epithelial injury in rat MN is related to the complement dose. Altered glomerular permeability is delayed with respect to the onset of complement activation. Once sufficient C5b-9 is formed, proteinuria can develop despite cessation of new MAC assembly, implying that C5b-9 persists after formation. Moreover, the C5b-7 MAC intermediate is not eliminated rapidly in this model. 相似文献
23.
Decay accelerating factor regulates complement activation on glomerular epithelial cells 总被引:5,自引:0,他引:5
R J Quigg A Nicholson-Weller A V Cybulsky J Badalamenti D J Salant 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(3):877-882
Epithelial cells of the glomerular capillary are the site of C5b-9 mediated injury in rat membranous nephropathy. We investigated the regulation of C activation by cultured glomerular epithelial cells (GEC). Rat and human GEC were more resistant to C injury by homologous C than heterologous C. In human GEC homologous C cytotoxicity was enhanced by antiserum to decay accelerating factor (DAF) indicating that homologous C activation was, at least in part, restricted by membrane DAF. Anti-DAF immunoprecipitated a 67-kDa protein from human glomeruli. In rat GEC, pronase and phosphatidylinositol-specific phospholipase C (which are known to inactivate human DAF) enhanced cytotoxicity by homologous C. Thus, DAF is present on human GEC in culture and in human kidney glomeruli, and a DAF-like protein is present on cultured rat GEC. These proteins regulate C activation in vitro and may play a role in controlling C activation on GEC in vivo. 相似文献
24.
Schofield DJ Pope AR Clementel V Buckell J Chapple SDj Clarke KF Conquer JS Crofts AM Crowther SR Dyson MR Flack G Griffin GJ Hooks Y Howat WJ Kolb-Kokocinski A Kunze S Martin CD Maslen GL Mitchell JN O'Sullivan M Perera RL Roake W Shadbolt SP Vincent KJ Warford A Wilson WE Xie J Young JL McCafferty J 《Genome biology》2007,8(11):R254-18
We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation. 相似文献
25.
Oligogalacturonic acids (OGAs), derived from plant cell wall pectin, have
been implicated in a number of signal transduction pathways involved in
growth, development and defense responses of higher plants. This study
investigates the size range of OGAs capable of inducing ethylene synthesis
in tomato plants, and demonstrates that in contrast with many other
effects, only short chain OGAs are active. Oligomers across a range of DP
from 2-15 were separated and purified to homogeneity by QAE-Sephadex anion
exchange chromatography using a novel elution system. The OGAs were applied
to tomato plants and assayed for their ability to induce ethylene gas
release and changes in steady state levels of mRNA encoding the ethylene
forming enzyme aminocyclopropane-1-carboxylic acid oxidase (ACO). The study
demonstrated that only OGAs in the size range of DP4-6 were active both in
eliciting ACO expression and in the production of ethylene.
相似文献
26.
27.
28.
Background
In a number of species males damage females during copulation, but the reasons for this remain unclear. It may be that males are trying to manipulate female mating behaviour or their life histories. Alternatively, damage may be a side-effect of male-male competition. In the black scavenger or dung fly Sepsis cynipsea (Diptera: Sepsidae) mating reduces female survival, apparently because males wound females during copulation. However, this damage does not seem to relate to attempted manipulation of female reproduction by males. Here we tested the hypothesis that harming females during mating is an incidental by-product of characters favoured during pre-copulatory male-male competition. We assessed whether males and their sons vary genetically in their ability to obtain matings and harm females, and whether more successful males were also more damaging. We did this by ranking males' mating success in paired competitions across several females whose longevity under starvation was subsequently measured. 相似文献29.
A change in twist of actin provides the force for the extension of the acrosomal process in limulus sperm: the false-discharge reaction 总被引:1,自引:5,他引:1 下载免费PDF全文
One of the most spectacular motions is the generation of the acrosomal process in the limulus sperm. On contact with the egg, the sperm generates a 60-mum-long process that literally drills its way through the jelly surrounding the egg. This irresversible reaction takes only a few seconds. We suggested earlier that this motion is driven by a change in twist of the actin filaments comprising the acrosomal process. In this paper we analyze the so-called false discharge, a reversible reaction, in which the acrosomal filament bundle extends laterally from the base of the sperm and not anteriorly from the apex. Unlike the true discharge, which is straight, the false discharge is helical. Before extension, the filament bundle is coiled about the base of the sperm. In the coil, the bundle is not smoothly bent but consists of arms (straight segments) and elbows (corners) so that the coil looks like a 14-sided polygon. The extension of the false discharge works as follows: starting at the base of the bundle, the filaments change their twist which concomitantly changes the orientations of the elbows relative to each other; that is, in the coil, the elbows all like in a common plane, but after the change in twist, the plane of each elbow is rotated to be perpendicular to that of its neighbors. This change transforms the bundle from a compact coil into an extended left- handed helix. Because the basal end of the bundle is unconstrained, the extension is lateral. The true discharge works the same way but starts at the apical end of the bundle. The apical end, however, is constrained by its passage through the nuclear canal, which directs the extention anteriorly. Unlike the false discharge, during the true discharge the elbows are melted out, making the reaction irreversible. This study shows that rapid movement can be regenerated by actin without myosin and gives us insight into the molecular mechanism. 相似文献
30.
Evolution at the tip and base of the X chromosome in an African population of Drosophila melanogaster 总被引:1,自引:0,他引:1
Hitchhiking effects of advantageous mutations have been invoked to explain
reduced polymorphism in regions of low crossing-over in Drosophila. Besides
reducing DNA heterozygosity, hitchhiking effects should produce strong
linkage disequilibrium and a frequency spectrum skewed toward an excess of
rare polymorphisms (compared to the neutral expectation). We measured DNA
polymorphism in a Zimbabwe population of D. melanogaster at three loci,
yellow, achaete, and suppressor of forked, located in regions of reduced
crossing-over. Similar to previously published surveys of these genomic
regions in other populations, we observed low levels of nucleotide
variability. However, the frequency spectrum was compatible with a neutral
model, and there was abundant evidence for recombination in the history of
the yellow and ac genes. Thus, some aspects of the data cannot be accounted
for by a simple hitchhiking model. An alternative hypothesis, background
selection, might be compatible with the observed patterns of linkage
disequilibrium and the frequency spectrum. However, this model cannot
account for the observed reduction in nucleotide heterozygosity. Thus,
there is currently no satisfactory theoretical model for the data from the
tip and base of the X chromosome in D. melanogaster.
相似文献