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41.
The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8alpha and CD8beta levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells' ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand. 相似文献
42.
Influence of vascular parameters on the effectiveness of intra-aortic balloon pumping: A model study
The intra-aortic balloon pump has been widely used as a temporary heart-assist device. In this investigation, a nonlinear
mathematical model of the arterial system and intra-aortic balloon pump was studied analytically. Thus, the influences of
a number of vascular parameters on the effectiveness of intra-aortic balloon pumping (IABP) were determined. The effects of
changes in vascular parameters of the model on a number of performance indexes were investigated. These performance indexes
(aortic mean diastolic pressure, aortic end diastolic pressure, cardiac output, coronary flow and phase differences between
the fundamental Fourier components of aortic root pressure and flow) were used as the criterion for an evaluation of the effectiveness
of the assist pump. The following vascular parameters were perturbed by four steps (±10%, ±20%) from the values in the standard
model: heart rate, peripheral resistance, left ventricular pressure, aortic elastance, aortic radius, arterial wall thickness,
and aortic length. This model was evaluated for a wide range of balloon-pump phase-control settings (assisted case) and for
the unassisted case (when the pump is disabled). It is concluded that changes in heart rate, peripheral resistance and left
ventricular pressure cause the most significant changes in pump performance.
Dr. Ohley is with the Datascope Corporation
Dr. Kao is with the Technicare Corporation 相似文献
43.
Fa -Ten Kao Judith Hartz Renata Horton Yale Nemerson Steven D. Carson 《Somatic Cell and Molecular Genetics》1988,14(4):407-410
Tissue factor, or coagulation factor III, is a membrane-bound glycoprotein and acts as a cofactor for factor VII-dependent initiation of blood coagulation. The tissue factor gene (F3) was previously assigned to human chromosome 1, region p21-pter. The present report has further refined the mapping position to 1p21-p22 using a cDNA probe for the tissue factor gene and in situ hybridization to metaphase chromosomes. 相似文献
44.
Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos 总被引:8,自引:2,他引:8
Yang HW; Hwang KJ; Kwon HC; Kim HS; Choi KW; Oh KS 《Human reproduction (Oxford, England)》1998,13(4):998-1002
In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture
environment differs from in-vivo conditions in that the oxygen
concentration is higher, and in such conditions the mouse embryos show a
higher concentration of reactive oxygen species (ROS) in simple culture
media. ROS are believed to cause damage to cell membranes and DNA
fragmentation in somatic cells. This study was conducted to ascertain the
level of H2O2 concentration within embryos and the morphological features
of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31
fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was
obtained from the IVF-embryo transfer programme. The relative intensity of
H2O2 concentrations within embryos was measured using
2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence
imaging and DNA fragmentation was observed with transmission electron
microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations
were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/-
SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and
unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed
only in fragmented embryos, and was absent in non-fragmented embryos.
Electron microscopic findings confirmed apoptotic bodies and cytoplasmic
condensation in the fragmented blastomeres. We conclude that there is a
direct relationship between increased H2O2 concentration and apoptosis, and
that further studies should be undertaken to confirm these findings.
相似文献
45.
46.
A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth 总被引:5,自引:0,他引:5
Kao HT Song HJ Porton B Ming GL Hoh J Abraham M Czernik AJ Pieribone VA Poo MM Greengard P 《Nature neuroscience》2002,5(5):431-437
Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases. 相似文献
47.
Fa-Ten Kao Suhong Tong Yiping Shen Jingwei Yu 《Somatic Cell and Molecular Genetics》1996,22(3):191-199
Three region-specific libraries for the entire human chromosome 18 were constructed using microdissection and MboI linker-adaptor
microcloning techniques. The libraries included 18pter-p11.1 (designated 18P library), 18q 11.1-q12.3 (18Q1 library), and
18q21.1-qter (18Q2 library). Samples of the microclones from each library were analyzed in detail. The insert sizes ranged
between 50–600 bp, with a mean of 180–220 bp for the three libraries. The libraries contained approximately 40–60% microclones
with unique sequence inserts. More than 30 unique sequence microclones from each library were analyzed by Southern blot hybridization
to demonstrate that they are human specific and were derived from chromosome 18. The human gemomic HindIII fragments hybridized
to each microclone were determined and microclones crosshybridized to rodent species were identified. These region-specific
libraries and the unique sequence microclones from the libraries are useful reagents for (1) isolating hughly polymorphic
microsatellite markers for refined linkage analysis, (2) identifying corresponding YAC, BAC or other clones with large inserts
for contig assembly and high resolution physical mapping, (3) isolating cDNA clones from the dissected region, and (4) convenient
sequencing of the microclones to prepare high density markers and sequence-tagged sites (STSs). Such applications have been
demonstrated in a series of similarly constructed microdissection libraries from other regions of the human genome. 相似文献
48.
Genomic Analysis of a Pathogenicity Island in Uropathogenic Escherichia coli CFT073: Distribution of Homologous Sequences among Isolates from Patients with Pyelonephritis, Cystitis, and CatheterAssociated Bacteriuria and from Fecal Samples 下载免费PDF全文
Urinary tract infection is the most frequently diagnosed kidney and urologic disease and Escherichia coli is by far the most common etiologic agent. Uropathogenic strains have been shown to contain blocks of DNA termed pathogenicity islands (PAIs) which contribute to their virulence. We have defined one of these regions of DNA within the chromosome of a highly virulent E. coli strain, CFT073, isolated from the blood and urine of a woman with acute pyelonephritis. The 57,988-bp stretch of DNA has characteristics which define PAIs, including a size greater than 30 kb, the presence of insertion sequences, distinct segmentation of K-12 and J96 origin, GC content (42.9%) different from that of total genomic DNA (50.8%), and the presence of virulence genes (hly and pap). Within this region, we have identified 44 open reading frames; of these 44, 10 are homologous to entries in the complete K-12 genome sequence, 4 are nearly identical to the sequences of E. coli J96 encoding the HlyA hemolysin, 11 encode P fimbriae, and 19 show no homology to J96 or K-12 entries. To determine whether sequences found within the junctions of the PAI of CFT073 were common to other uropathogenic strains of E. coli, 11 probes were isolated along the length of the PAI and were hybridized to dot blots of genomic DNA isolated from clinical isolates (67 from patients with acute pyelonephritis, 38 from patients with cystitis, 49 from patients with catheter-associated bacteriuria, and 27 from fecal samples). These sequences were found significantly more often in strains associated with the clinical syndromes of acute pyelonephritis (79%) and cystitis (82%) than in those associated with catheter-associated bacteriuria (58%) and in fecal strains (22%) (P < 0.001). From these regions, we have identified a putative iron transport system and genes other than hly and pap that may contribute to the virulent phenotype of uropathogenic E. coli strains. 相似文献
49.
Actions of some anions on electrical properties and mechanical threshold of frog twitch muscle 总被引:9,自引:1,他引:9
1. Using two micro-electrodes in a point-voltage clamp technique, the effects of the lyotropic anions, NO(3) (-), Br(-), I(-), SCN(-), and CH(3)SO(4) (-), and of SO(4) (2-) on the mechanical threshold and electrical properties of frog sartorius muscle were studied.2. In chloride Ringer solution the spike threshold was -59 mV, mechanical threshold -48 mV, and the threshold for delayed rectification of the total current at about 100 msec -52 mV.3. When Cl(-) was replaced by one of the lyotropic anions, the effective resistance determined at -100 mV tended to increase. But, because of the variability of the effective resistance in individual fibres, most lyotropic anions did not cause a statistically significant increase in the effective resistance. Only I(-) and SO(4) (2-) significantly increased the effective resistance.4. Most lyotropic anions had no significant effect on the spike threshold; I(-), at 58 mM, lowered it slightly. Sulphate raised the threshold.5. Tetrodotoxin (0.1 mug/ml.) abolished the spikes, but did not affect the mechanical and delayed rectification thresholds. It was, therefore, used to pre-treat all preparations for determining these thresholds.6. All lyotropic anions lowered the mechanical and the delayed rectification thresholds, the order of effectiveness being approximately SCN(-) > I(-) > NO(3) (-) > CH(3)SO(4) (-) > Br(-). As in Cl(-) Ringer, the two thresholds lay very close together in every case. Sulphate raised slightly both the mechanical and delayed rectification thresholds, again in close parallel.7. This close agreement of the mechanical and delayed rectification thresholds is not caused by movement artifact, because in fibres in which visible contractions were eliminated with hypertonic solutions the delayed rectification thresholds were the same as those in contracting fibres.8. In spite of the close agreement, reasons are given to doubt a direct causal relationship between the mechanical and delayed rectification thresholds.9. Nitrate apparently had little effect on the rate of inactivation of the outward current, or on the relation between steady-state inactivation and membrane potential. 相似文献
50.
Enterotoxicity and cytotoxicity of Vibrio parahaemolyticus thermostable direct hemolysin in in vitro systems 总被引:5,自引:0,他引:5 下载免费PDF全文
Raimondi F Kao JP Fiorentini C Fabbri A Donelli G Gasparini N Rubino A Fasano A 《Infection and immunity》2000,68(6):3180-3185
Vibrio parahaemolyticus is a marine bacterium known to be a common cause of seafood gastroenteritis worldwide. The thermostable direct hemolysin (TDH) has been proposed to be a major virulence factor of V. parahaemolyticus. TDH causes intestinal fluid secretion as well as cytotoxicity in a variety of cell types. In this study, we investigated the interplay between the hemolysin's enterotoxic and cytotoxic effects by using both human and rat cell monolayers. As revealed by microspectrofluorimetry, the toxin causes a dose-dependent increase in intracellular free calcium in both Caco-2 and IEC-6 cells. This effect was reversible only when low toxin concentrations were tested. The TDH-activated ion influx pathway is not selective for calcium but admits ions such sodium and manganese as well. Furthermore, in the same range of concentration, the hemolysin triggers a calcium-dependent chloride secretion. At high concentrations, TDH induces a dose-dependent but calcium-independent cell death as assessed by functional, biochemical, and morphological assays. 相似文献