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71.
72.
Jain RK; Piskorz CF; Huang BG; Locke RD; Han HL; Koenig A; Varki A; Matta KL 《Glycobiology》1998,8(7):707-717
The selectins interact in important normal and pathological situations with
certain sialylated, fucosylated glycoconjugate ligands containing sialyl
Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone
into the synthesis of sialylated and sulfated Lewisxanalogs as competitive
ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and
PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure,
we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++
+-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L
and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies
have shown that sulfate esters can replace sialic acid in some selectin
ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. ,
Nature, 361, 555, 1993). Based upon these observations, we hypothesized
that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of
interacting with L- and P-selectin. To examine this hypothesis, we
synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++
+-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better
than sialyl Lexfor P and L selectin, respectively. We also report the
synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1-
3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to
be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe.
Combining this with our knowledge of Core 2 branched structures, we have
synthesized a molecule that is 5- to 6-fold better at inhibiting L- and
P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures,
substitution of a sulfate ester group for a sialic acid residue in such a
molecule resulted in a considerable loss of inhibition ability. Thus, the
combination of a sialic acid residue on the primary (beta1-3) arm, and a
modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2
structure generated a monovalent synthetic oliogosaccharide inhibitor
superior to SLexfor both L- and P-selectin.
相似文献
73.
Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro
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The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (ρO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; ρO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it. 相似文献
74.
A comparison of methods for estimating the transition:transversion ratio from DNA sequences 总被引:1,自引:0,他引:1
Estimation of the ratio of the rates of transitions to transversions (TI:TV ratio) for a collection of aligned nucleotide sequences is important because it provides insight into the process of molecular evolution and because such estimates may be used to further model the evolutionary process for the sequences under consideration. In this paper, we compare several methods for estimating the TI:TV ratio, including the pairwise method [TREE 11 (1996) 158], a modification of the pairwise method due to Ina [J. Mol. Evol. 46 (1998) 521], a method based on parsimony (TREE 11 (1996) 158), a method due to Purvis and Bromham [J. Mol. Evol. 44 (1997) 112] that uses phylogenetically independent pairs of sequences, the maximum likelihood method, and a Bayesian method [Bioinformatics 17 (2001) 754]. We examine the performance of each estimator under several conditions using both simulated and real data. 相似文献
75.
76.
77.
Alberto Pilotto Francesco Panza Massimiliano Copetti Matteo Simonato Daniele Sancarlo Pietro Gallina Timo Strandberg MPI_AGE Project Investigators 《PloS one》2015,10(6)
Background
Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that statin treatment in older patients with DM was differentially effective across strata of mortality risk assessed by the Multidimensional Prognostic Index (MPI), based on information collected with the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA).Methods
In this retrospective observational study, we estimated the mortality risk in 1712 community-dwelling subjects with DM ≥ 65 years who underwent a SVaMA evaluation to establish accessibility to homecare services/nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) risk of mortality at baseline and propensity score-adjusted hazard ratios (HR) of three-year mortality were calculated according to statin treatment.Results
Higher MPI-SVaMA scores were associated with lower rates of statin treatment (MPI-SVaMA-1 = 39% vs MPI-SVaMA-2 = 36% vs MPI-SVaMA-3 = 24.9%. p<0.001) and higher three-year mortality (MPI-SVaMA-1 = 12.9% vs MPI-SVaMA-2 = 24% vs MPI-SVaMA-3 = 34.4%, p<0.001). After adjustment for propensity score quintiles, statin treatment was significantly associated with lower three-year mortality irrespective of MPI-SVaMA group (interaction test p = 0.303). HRs [95% confidence interval (CI)] were 0.19 (0.14–0.27), 0.28 (0.21–0.36), and 0.26 (0.20–0.34) in the MPI-SVaMA-1, MPI-SVaMA-2, and MPI-SVaMA-3 groups, respectively. Subgroup analyses showed that statin treatment was also beneficial irrespective of age. HRs (95% CI) were 0.21 (0.15–0.31), 0.26 (0.20–0.33), and 0.26 (0.20–0.35) among patients aged 65–74, 75–84, and ≥ 85 years, respectively (interaction test p=0.812).Conclusions
Statin treatment was significantly associated with reduced three-year mortality independently of age and multidimensional impairment in community-dwelling frail older patients with DM. 相似文献78.
Julia?Misiewicz Sergii?Afonin Stephan?L.?Grage Jonas?van den?Berg Erik?Strandberg Parvesh?Wadhwani Anne?S.?UlrichEmail author 《Journal of biomolecular NMR》2015,61(3-4):287-298
Membrane composition is a key factor that regulates the destructive activity of antimicrobial peptides and the non-leaky permeation of cell penetrating peptides in vivo. Hence, the choice of model membrane is a crucial aspect in NMR studies and should reflect the biological situation as closely as possible. Here, we explore the structure and dynamics of the short multifunctional peptide BP100 using a multinuclear solid-state NMR approach. The membrane alignment and mobility of this 11 amino acid peptide was studied in various synthetic lipid bilayers with different net charge, fluidity, and thickness, as well as in native biomembranes harvested from prokaryotic and eukaryotic cells. 19F-NMR provided the high sensitivity and lack of natural abundance background that are necessary to observe a labelled peptide even in protoplast membranes from Micrococcus luteus and in erythrocyte ghosts. Six selectively 19F-labeled BP100 analogues gave remarkably similar spectra in all of the macroscopically oriented membrane systems, which were studied under quasi-native conditions of ambient temperature and full hydration. This similarity suggests that BP100 has the same surface-bound helical structure and high mobility in the different biomembranes and model membranes alike, independent of charge, thickness or cholesterol content of the system. 31P-NMR spectra of the phospholipid components did not indicate any bilayer perturbation, so the formation of toroidal wormholes or micellarization can be excluded as a mechanism of its antimicrobial or cell penetrating action. However, 2H-NMR analysis of the acyl chain order parameter profiles showed that BP100 leads to considerable membrane thinning and thereby local destabilization. 相似文献
79.
Marcelo H Petri Minoru Satoh Beatriz T Martin-Marquez Raul Vargas-Ramírez Luis J Jara Miguel A Saavedra Claudia Cruz-Gonzalez Lilia Andrade-Ortega Olga Vera-Lastra Mario Salazar-Páramo Rosa E Prieto-Parra Laura Gonzalez-Lopez Jorge I Gamez-Nava Hermes U Ramírez-Sánchez Jason YF Chan Steven J Ross Edward KL Chan Mónica Vázquez-Del Mercado 《Arthritis research & therapy》2013,15(2):R48
Introduction
Autoantibodies and clinical manifestations in polymyositis/dermatomyositis (PM/DM) are affected by both genetic and environmental factors. The high prevalence of DM and anti-Mi-2 in Central America is thought to be associated with the high UV index of the area. The prevalences of autoantibodies and the clinical manifestations of PM/DM were evaluated comparing two cohorts in Mexico.Methods
Ninety-five Mexican patients with PM/DM (66 DM, 29 PM; 67 Mexico City, 28 Guadalajara) were studied. Autoantibodies were characterized by immunoprecipitation using 35S-methionine labeled K562 cell extract. Clinical information was obtained from medical records.Results
DM represented 69% of PM/DM and anti-Mi-2 was the most common autoantibody (35%), followed by anti-p155/140 (11%); however, anti-Jo-1 was only 4%. The autoantibody profile in adult-onset DM in Mexico City versus Guadalajara showed striking differences: anti-Mi-2 was 59% versus 12% (P = 0.0012) whereas anti-p155/140 was 9% versus 35% (P = 0.02), respectively. A strong association of anti-Mi-2 with DM was confirmed and when clinical features of anti-Mi-2 (+) DM (n = 30) versus anti-Mi-2 (-) DM (n = 36) were compared, the shawl sign (86% versus 64%, P < 0.05) was more common in the anti-Mi-2 (+) group (P = 0.0001). Levels of creatine phosphokinase (CPK) were higher in those who were anti-Mi-2 (+) but they responded well to therapy.Conclusions
Anti-Mi-2 has a high prevalence in Mexican DM and is associated with the shawl sign and high CPK. The prevalence of anti-Mi-2 and anti-p155/140 was significantly different in Mexico City versus Guadalajara, which have a similar UV index. This suggests roles of factors other than UV in anti-Mi-2 antibody production. 相似文献80.
Michael Mahler Cristina Gascon Sima Patel Angela Ceribelli Marvin J Fritzler Andreas Swart Edward KL Chan Minoru Satoh 《Arthritis research & therapy》2013,15(2):R50