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181.
PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow 总被引:1,自引:0,他引:1
Zou X Shinde Patil VR Dagia NM Smith LA Wargo MJ Interliggi KA Lloyd CM Tees DF Walcheck B Lawrence MB Goetz DJ 《American journal of physiology. Cell physiology》2005,289(2):C415-C424
P-selectin glycoprotein ligand-1 (PSGL-1) has been proposed as an important tethering ligand for E-selectin and is expressed at a modest level on human leukocytes. Sialyl Lewis x (sLex)-like glycans bind to E-selectin and are expressed at a relatively high level on circulating leukocytes. It is unclear whether PSGL-1 has unique biochemical attributes that contribute to its role as an E-selectin ligand. To probe this issue, we conjugated microspheres with either sLex or PSGL-1 purified from myeloid cells (neutrophils and HL-60) and compared their adhesion to endothelial expressed E-selectin under defined shear conditions. We found that both sLex and PSGL-1 microspheres adhere to 4 h of IL-1-activated human umbilical vein endothelial cells predominantly through E-selectin. Analysis of the adhesion revealed that the rate of initial tethering of the PSGL-1 microspheres to E-selectin was significantly greater than the rate of initial tethering of the sLex microspheres despite the fact that the sLex microspheres tested had higher ligand densities than the PSGL-1 microspheres. We also found that pretreatment of the PSGL-1 or sLex microspheres with HECA-452 had no significant effect on initial tethering to E-selectin. These results support the hypotheses that 1) PSGL-1 is a high-efficiency tethering ligand for E-selectin, 2) ligand biochemistry can significantly influence initial tethering to E-selectin, and 3) PSGL-1 tethering to E-selectin can occur via non-HECA-452 reactive epitopes. adhesion; leukocyte; inflammation 相似文献
182.
Complex determinants in human immunodeficiency virus type 1 envelope gp120 mediate CXCR4-dependent infection of macrophages 下载免费PDF全文
Ghaffari G Tuttle DL Briggs D Burkhardt BR Bhatt D Andiman WA Sleasman JW Goodenow MM 《Journal of virology》2005,79(21):13250-13261
Host cell range, or tropism, combined with coreceptor usage defines viral phenotypes as macrophage tropic using CCR5 (M-R5), T-cell-line tropic using CXCR4 (T-X4), or dually lymphocyte and macrophage tropic using CXCR4 alone or in combination with CCR5 (D-X4 or D-R5X4). Although envelope gp120 V3 is necessary and sufficient for M-R5 and T-X4 phenotypes, the clarity of V3 as a dominant phenotypic determinant diminishes in the case of dualtropic viruses. We evaluated D-X4 phenotype, pathogenesis, and emergence of D-X4 viruses in vivo and mapped genetic determinants in gp120 that mediate use of CXCR4 on macrophages ex vivo. Viral quasispecies with D-X4 phenotypes were associated significantly with advanced CD4+-T-cell attrition and commingled with M-R5 or T-X4 viruses in postmortem thymic tissue and peripheral blood. A D-X4 phenotype required complex discontinuous genetic determinants in gp120, including charged and uncharged amino acids in V3, the V5 hypervariable domain, and novel V1/V2 regions distinct from prototypic M-R5 or T-X4 viruses. The D-X4 phenotype was associated with efficient use of CXCR4 and CD4 for fusion and entry but unrelated to levels of virion-associated gp120, indicating that gp120 conformation contributes to cell-specific tropism. The D-X4 phenotype describes a complex and heterogeneous class of envelopes that accumulate multiple amino acid changes along an evolutionary continuum. Unique gp120 determinants required for the use of CXCR4 on macrophages, in contrast to cells of lymphocytic lineage, can provide targets for development of novel strategies to block emergence of X4 quasispecies of human immunodeficiency virus type 1. 相似文献
183.
Cultural competence is used (often implicitly) to make decisions in human service settings. When therapists make decisions about whether or not a particular service will be offered, they place themselves in a position where their own competence can be judged. Using narrative data on independence and the elderly, we apply Edgerton's idea of the cloak of competence to demonstrate this doubling effect. 相似文献
184.
Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement 下载免费PDF全文
Anavekar N Bais R Carney S Davidson J Eris J Gallagher M Johnson D Jones G Sikaris K Lonergan M Ludlow M Mackie J Mathew T May S McBride G Meerkin M Peake M Power D Snelling P Voss D Walker R;Australian Creatinine Consensus Working Group 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2005,26(3):81-86
The systematic staging of chronic kidney disease (CKD) by glomerular filtration measurement and proteinuria has allowed the development of rational and appropriate management plans. One of the barriers to early detection of CKD is the lack of a precise, reliable and consistent measure of kidney function.The most common measure of kidney function is currently serum creatinine concentration. It varies with age, sex, muscle mass and diet, and interlaboratory variation between measurements is as high as 20%.The reference interval for serum creatinine concentration includes up to 25% of people (particularly thin, elderly women) who have an estimated glomerular filtration rate (eGFR) that is significantly reduced (< 60 mL/min/1.73 m). The recent publication of a validated formula (MDRD) to estimate GFR from age, sex, race and serum creatinine concentration, without any requirement for measures of body mass, allows pathology laboratories to "automatically" generate eGFR from data already acquired. Automatic laboratory reporting of eGFR calculated from serum creatinine measurements would help to identify asymptomatic kidney dysfunction at an earlier stage. eGFR correlates well with complications of CKD and an increased risk of adverse outcomes such as cardiovascular morbidity and mortality. We recommend that pathology laboratories automatically report eGFR each time a serum creatinine test is ordered in adults. As the accuracy of eGFR is suboptimal in patients with normal or near-normal renal function, we recommend that calculated eGFRs above 60 mL/min/1.73 m be reported by laboratories as "> 60 mL/min/1.73 m", rather than as a precise figure. 相似文献
185.
In plants, more favourable environmental conditions can lead to dramatic increases in both mean fitness and variance in fitness. This results in data that violate the equality-of-variance assumption of anova, a problem that most empiricists would address by log-transforming fitness values. Using heuristic data sets and simple simulations, we show that anova on log-transformed fitness consistently fails to match the outcome of selection in a heterogeneous environment or its sensitivity to environmental frequency. Only anova based on relative fitness within environments accurately predicts the sensitivity of genotype selection to the frequency of alternative environments. Parallel analyses of variance based on absolute fitness and relative fitness can bracket the expected success of alternative genotypes under hard and soft selection, respectively. For example, for Sinapis arvensis growing in full sun and partial shade treatments, families achieving high fitness in the best environment are favoured under hard selection, whereas soft selection favours different families that achieve consistently good performance across environments. Based on these findings, we recommend that log-transformation of fitness should no longer be standard practice in ecological genetics studies. Weighted anova is a preferable method for dealing with unequal variances, and investigators should also make greater use of techniques such as quantile regression or resampling to describe and evaluate fitness variation across heterogeneous environments. 相似文献
186.
Macpherson JL Boyd MP Arndt AJ Todd AV Fanning GC Ely JA Elliott F Knop A Raponi M Murray J Gerlach W Sun LQ Penny R Symonds GP Carr A Cooper DA 《The journal of gene medicine》2005,7(5):552-564
BACKGROUND: An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. METHODS: Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. RESULTS: The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. CONCLUSIONS: The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection. 相似文献
187.
Huang J Shi J Molle V Sohlberg B Weaver D Bibb MJ Karoonuthaisiri N Lih CJ Kao CM Buttner MJ Cohen SN 《Molecular microbiology》2005,58(5):1276-1287
A complex programme of regulation governs gene expression during development of the morphologically and biochemically complex eubacterial genus Streptomyces. Earlier work has suggested a model in which 'higher level' pleiotropic regulators activate 'pathway-specific' regulators located within chromosomal gene clusters encoding biosynthesis of individual antibiotics. We used mutational analysis and adventitious overexpression of key Streptomyces coelicolor regulators to investigate functional interactions among them. We report here that cluster-situated regulators (CSRs) thought to be pathway-specific can also control other antibiotic biosynthetic gene clusters, and thus have pleiotropic actions. Surprisingly, we also find that CSRs exhibit growth-phase-dependent control over afsR2/afsS, a 'higher level' pleiotropic regulatory locus not located within any of the chromosomal gene clusters it targets, and further demonstrate that cross-regulation by CSRs is modulated globally and differentially during the S. coelicolor growth cycle by the RNaseIII homologue AbsB. Our results, which reveal a network of functional interactions among regulators that govern production of antibiotics and other secondary metabolites in S. coelicolor, suggest that revision of the currently prevalent view of higher-level versus pathway-specific regulation of secondary metabolism in Streptomyces species is warranted. 相似文献
188.
Oppong KA Ellis CD Laufersweiler MC O'Neil SV Wang Y Soper DL Baize MW Wos JA De B Bosch GK Fancher AN Lu W Suchanek MK Wang RL Demuth TP 《Bioorganic & medicinal chemistry letters》2005,15(19):4291-4294
A novel diazocan containing dipeptide mimetic was synthesized via reductive N-N bond cleavage of a pyrazolidino-pyrazolidine using Raney-Ni and evaluated as an ICE inhibitor. This versatile 8-membered ring containing scaffold possesses an N-5 ring nitrogen that was used to explore structure-activity relationships in a cell-based assay measuring inhibition of interleukin-1beta. 相似文献
189.
Tang Y Finlay JA Kowalke GL Meyer AE Bright FV Callow ME Callow JA Wendt DE Detty MR 《Biofouling》2005,21(1):59-71
Hybrid sol-gel-derived xerogel films prepared from 45/55 (mol ratio) n-propyltrimethoxysilane (C3-TMOS)/tetramethylorthosilane (TMOS), 2/98 (mol ratio) bis[3-(trimethoxysilyl)propyl]-ethylenediamine (enTMOS)/tetraethylorthosilane (TEOS), 50/50 (mol ratio) n-octyltriethoxysilane (C8-TEOS)/TMOS, and 50/50 (mol ratio) 3,3,3-trifluoropropyltrimethoxysilane (TFP-TMOS)/TMOS were found to inhibit settlement of zoospores of the marine fouling alga Ulva (syn. Enteromorpha) relative to settlement on acid-washed glass and give greater release of settled zoospores relative to glass upon exposure to pressure from a water jet. The more hydrophobic 50/50 C8-TEOS/TMOS xerogel films had the lowest critical surface tension by comprehensive contact angle analysis and gave significantly greater release of 8-day Ulva sporeling biomass after exposure to turbulent flow generated by a flow channel than the other xerogel surfaces or glass. The 50/50 C8-TEOS/TMOS xerogel was also a fouling release surface for juveniles of the tropical barnacle Balanus amphitrite. X-ray photon electron data indicated that the alkylsilyl residues of the C3-TMOS-, C8-TEOS-, and TFP-TMOS-containing xerogels were located on the surface of the xerogel films (in a vacuum), which contributes to the film hydrophobicity. Similarly, the amine-containing silyl residues of the enTMOS/TEOS films were located at the surface of the xerogel films, which contributes to the more hydrophilic character and increased critical surface tension of these films. 相似文献
190.
Mice possessing the lethal yellow mutation (C57BL/6J A(y)/a) become obese and develop hyperleptinemia and leptin resistance as they age. To determine the relationship between altered leptin physiology and reproductive function in these mice, we compared body weight (BW), serum leptin concentration, ovulation rate, and in vitro blastocyst development among 120- and 180-d-old lethal yellow and black non-mutant (a/a) mice. Estrous female yellow and black mice were mated with fertile black males. Oviducts were flushed approximately 36 h after mating and the recovered embryos were cultured for 96 h. BW, serum leptin levels, and the leptin:BW ratio differed among groups as follows: 180-d yellow > 120-d yellow > 180-d black = 120-d black. Ovulation rate was similar among 120-d yellow and black, and 180-d black mice. Among 180-d yellow mice, five of twelve mice failed to ovulate, but the other seven mice ovulated a similar number of oocytes as their black counterparts (8.4 +/- 0.9 versus 8.0 +/- 1.3). Non-ovulators had higher (P < 0.05) leptin levels (56.6 +/- 1.8 ng x mL(-1)) than ovulators (46.2 +/- 3.5), but BW did not differ significantly. Fewer embryos from 180-d yellow mice reached the blastocyst stage in culture than did the embryos from black mice (55% versus 83%, P < 0.05). Moreover, blastocyst development in 180-d old yellow mice negatively correlated with leptin levels (r = -0.797, P = 0.032) and leptin:BW ratio (r = -0.847, P = 0.016), but not with BW. Declining reproductive function in lethal yellow mice appears to be related to increasing levels of leptin and progression of leptin resistance. 相似文献