Fluid shear stress activation of IkappaB kinase is integrin-dependent

Vascular endothelial cells (ECs), forming a boundary between the circulating blood and the vessel wall, are constantly subjected to fluid shear stress due to blood flow. The aim of this study was to determine the role of the recently identified IkappaB kinases (IKKs) in shear stress activation of NF-kappaB and to elucidate the upstream signaling mechanism that mediates IKK activation. Our results demonstrate that IKKs in ECs are activated by shear stress in a rapid and transient manner. This IKK activation is followed by IkappaB degradation and NF-kappaB translocation into the nucleus. Transfection of plasmids encoding catalytic inactive mutants of IKKs, i.e. hemagglutinin (HA)-IKKalpha(K44M) and HA-IKKbeta(K44A), inhibits shear stress-induced NF-kappaB translocation. In addition, constructs encoding antisense IKKs, i.e. HA-IKKalpha(AS) and HA-IKKbeta(AS), attenuate shear stress induction of a promoter driven by the kappaB enhancer element. Preincubation of the EC monolayer with a monoclonal anti-alphavbeta3 integrin antibody (clone LM609) attenuates shear stress induction of IKK. Inhibition of tyrosine kinases by genistein causes a similar down-regulating effect. These results suggest that the integrin-mediated signaling pathway regulates NF-kappaB through IKKs in ECs in response to shear stress.     

Influence of alleles of apolipoprotein E on restenosis after coronary angioplasty in women

Galanin is a 29-amino acid peptide and widely distributed in the brain, although its significance in the control of neural activities is undefined. In the present study, we describe the effects of galanin on the electrically evoked release of dopamine in the rat central nervous system. In addition, to elucidate a possible role of galanin in the regulation of dopaminergic transmission in hypertension, we examined whether the effect of galanin on dopamine release might be altered in the central nervous system of spontaneously hypertensive rats (SHR). Galanin (1 x 10(-8) to 1 x 10(-7) mol/L) inhibited the stimulation (1 Hz)-evoked [3H]dopamine release by a comparable amount in striatal slices of Sprague-Dawley rats, although the basal release of dopamine was not affected by the peptide. In the striatum of SHR, the electrical stimulation (1 Hz)-evoked [3H]dopamine release was significantly smaller than in the striatum of Wistar-Kyoto (WKY) rats. However, the inhibitory effect of galanin on the stimulation-evoked [3H]dopamine release was significantly more pronounced in SHR than in WKY rats. These results show that galanin significantly reduced the release of dopamine in rat striatum. Furthermore, the greater inhibitory effect of galanin on dopamine release in SHR suggests that galanin might actively participate in the regulation of dopaminergic nerve activity in hypertension.     

综观PC产业三大变化方向

80年代开始,PC就一直影响人们的生活,从最初的8086/8088架构,到现在GHz的Pentium时代,PC创造了半导体、PC外围、零部件与光电产业的庞大商机.时光进入2004年,随着数字家庭或者说是多媒体中心风潮的到来,使得大家的焦点不再只是单纯放在微处理器的时脉速度,取而代之的是无线局域网的能力、与视觉享受有关的绘图处理器与监视器、高品质的音效及内存容量与传输速度.     

Intraoperative radiotherapy in 1997

Codon usage bias of 1,117 Drosophila melanogaster genes, as well as fewer D. pseudoobscura and D. virilis genes, was examined from the perspective of relative abundance of isoaccepting tRNAs and their changes during development. We found that each amino acid contributes about equally and highly significantly to overall codon usage bias, with the exception of Asp which had very low contribution to overall bias. Asp was also the only amino acid that did not show a clear preference for one of its synonymous codons. Synonymous codon usage in Drosophila was consistent with "optimal" codons deduced from the isoaccepting tRNA availability. Interestingly, amino acids whose major isoaccepting tRNAs change during development did not show as strong bias as those with developmentally unchanged tRNA pools. Asp is the only amino acid for which the major isoaccepting tRNAs change between larval and adult stages. We conclude that synonymous codon usage in Drosophila is well explained by tRNA availability and is probably influenced by developmental changes in relative abundance.     

A closed culture system for the ex vivo transduction and expansion of human T lymphocytes

The purpose of this qualitative study was to explore traditional beliefs and practices related to pregnancy and childbirth among Native American women and examine the relationship of these beliefs and practices to current use of prenatal care. Focus groups of elders and young women were held and the data analyzed with the Ethnograph software. The central theme was the breakdown in transmission of cultural wisdom among Native American women. The major causes described by women were federal assimilation policies and deaths of elders. Major factors influencing young women's nonutilization of prenatal care were this breakdown, the "Western model" of prenatal care, substance abuse, and domestic violence. Recommendations for improving the use of prenatal care are grounded in the reality that Native American women live in two different worlds. Prenatal care should be reconceptualized as traditional cultural wisdom, with the majority of care provided by natural helpers in the Native American community, including tribal elders, grandmothers, and aunts in collaboration with licensed providers.     

Surgery of the pudendal nerve in various types of perineal pain: course and results

In 1989, we reported our thoughts on the neurophysiological and anatomic aspects of pudendal nerve involvement in certain types of perinal pain. Since that time, the surgical approach has been modified. Here we report our follow-up of 40 patients with 48 operated nerves. Follow-up ranged from 6 months to 7 years and outcome revealed improvement in 67% and no change in 33%. Thus surgery had been useful in two-thirds of the cases; in 44% of the patients, there was either a frank improvement or no change. Early diagnosis appears to be the determining factor in improving results. Operating for the canal syndrome must be performed before lesions to the nervous trunk become too important.     

Synergistic cooperation between phorbol ester and IFN-gamma for induction of nitric oxide synthesis in murine peritoneal macrophages

The role of protein kinase C (PKC) in the induction of nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. Phorbol ester, a PKC activator, had no effect on NO synthesis by itself, whereas IFN-gamma alone had modest activity. When phorbol ester was used in combination with IFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA, as determined by Northern blotting. The optimal effect of phorbol ester was shown at 6 h after treatment with IFN-gamma. Phorbol ester also induced the release of NO to the incubation medium by bacillus Calmette-Guerin-infected peritoneal macrophages. Prolonged incubation of cells with phorbol ester, which down-regulates PKC activity, abolished the synergistic cooperative effect on NO production with IFN-gamma. In addition, such PKC inhibitors as staurosporin or polymyxin B reduced NO production induced by IFN-gamma plus phorbol ester. When the cells were treated with both actinomycin D and phorbol ester after IFN-gamma stimulation, more NO was produced and more iNOS mRNA was expressed than in the cells treated with actinomycin D alone. On the basis of these observations, we conclude that PKC might not be directly involved in the expression of NO synthase, but, instead, might be involved in the stabilization of the iNOS mRNA already expressed by the treatment of IFN-gamma.