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311.
312.
Application of 14CB-aminopropionitrile (BAPN) to the skin of rats followed by measurement of urinary radioactivity was used for comparative studies of the absorption of 14C-BAPN fumarate and 14C-BAPN free base (F.B.). 14C-BAPN (F.B.) was absorbed more rapidly and to a greater extent than the fumarate salt. Six hours after topical administration of 14C-BAPN (F.B.) only traces of 14C were found on the skin and less than 1% of the dose within the skin section suggesting rapid drug absorption. Lysyl oxidase activity of sponge granuloma tissue was significantly inhibited by a single small dose (20 μl) of BAPN (F.B.) applied to the intact skin over the implant. Chronic application of twice daily 5 μl doses of BAPN (F.B.) significantly inhibited lysyl oxidase of the granuloma tissue underlying the area of topical application as well as that on the opposite side not receiving BAPN. Extractibility of collagen was significantly increased only in the granuloma tissue under the skin receiving BAPN. 相似文献
313.
Calcium has been identified as having an important role as a transmembrane messenger in the activation signal for lymphocytes. To additionally examine this model, we evaluated the effect of calcium channel blocking drugs (verapamil, nifedipine, and diltiazem) on lymphocyte activation. In these studies we found that the drugs inhibit, in a dose-dependent fashion, the proliferation of T cells and the appearance of certain activation antigens after mitogen stimulation. This appears to result from the marked decrease in mitogen-induced 45calcium (45Ca+2) influx secondary to the addition of these agents. In addition, T cell proliferation resulting from IL 2 binding to its receptor is also suppressed by the calcium channel blocking drugs. These data suggest that the passive calcium channel plays a pivotal role in both the initial activation of T cells after ligand-receptor interaction and the ongoing signal for proliferation provided by IL 2 binding to its receptor. 相似文献
314.
Manon JM van Oosten Radboud JEM Dolhain Jan W Koper Elisabeth FC van Rossum Marieke Emonts Khik H Han Jacques MGW Wouters Johanne MW Hazes Steven WJ Lamberts Richard A Feelders 《Arthritis research & therapy》2010,12(4):R159
Introduction
The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity. 相似文献315.
Anna E van der Windt Esther Haak Ruud HJ Das Nicole Kops Tim JM Welting Marjolein MJ Caron Niek P van Til Jan AN Verhaar Harrie Weinans Holger Jahr 《Arthritis research & therapy》2010,12(3):R100
Introduction
Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype. 相似文献316.
Carlos Oscar Sanchez Sorzano Cédric Messaoudi Matthias Eibauer JR Bilbao-Castro R Hegerl S Nickell S Marco JM Carazo 《BMC bioinformatics》2009,10(1):124-11
Background
Tilt series are commonly used in electron tomography as a means of collecting three-dimensional information from two-dimensional projections. A common problem encountered is the projection alignment prior to 3D reconstruction. Current alignment techniques usually employ gold particles or image derived markers to correctly align the images. When these markers are not present, correlation between adjacent views is used to align them. However, sequential pairwise correlation is prone to bias and the resulting alignment is not always optimal. 相似文献317.
Ian Walsh Alberto JM Martin Catherine Mooney Enrico Rubagotti Alessandro Vullo Gianluca Pollastri 《BMC bioinformatics》2009,10(1):195-19
Background
Proteins, especially larger ones, are often composed of individual evolutionary units, domains, which have their own function and structural fold. Predicting domains is an important intermediate step in protein analyses, including the prediction of protein structures. 相似文献318.
Ian Walsh Davide Baù Alberto JM Martin Catherine Mooney Alessandro Vullo Gianluca Pollastri 《BMC structural biology》2009,9(1):5-20
Background
Prediction of protein structures from their sequences is still one of the open grand challenges of computational biology. Some approaches to protein structure prediction, especially ab initio ones, rely to some extent on the prediction of residue contact maps. Residue contact map predictions have been assessed at the CASP competition for several years now. Although it has been shown that exact contact maps generally yield correct three-dimensional structures, this is true only at a relatively low resolution (3–4 Å from the native structure). Another known weakness of contact maps is that they are generally predicted ab initio, that is not exploiting information about potential homologues of known structure.Results
We introduce a new class of distance restraints for protein structures: multi-class distance maps. We show that C α trace reconstructions based on 4-class native maps are significantly better than those from residue contact maps. We then build two predictors of 4-class maps based on recursive neural networks: one ab initio, or relying on the sequence and on evolutionary information; one template-based, or in which homology information to known structures is provided as a further input. We show that virtually any level of sequence similarity to structural templates (down to less than 10%) yields more accurate 4-class maps than the ab initio predictor. We show that template-based predictions by recursive neural networks are consistently better than the best template and than a number of combinations of the best available templates. We also extract binary residue contact maps at an 8 Å threshold (as per CASP assessment) from the 4-class predictors and show that the template-based version is also more accurate than the best template and consistently better than the ab initio one, down to very low levels of sequence identity to structural templates. Furthermore, we test both ab-initio and template-based 8 Å predictions on the CASP7 targets using a pre-CASP7 PDB, and find that both predictors are state-of-the-art, with the template-based one far outperforming the best CASP7 systems if templates with sequence identity to the query of 10% or better are available. Although this is not the main focus of this paper we also report on reconstructions of C α traces based on both ab initio and template-based 4-class map predictions, showing that the latter are generally more accurate even when homology is dubious.Conclusion
Accurate predictions of multi-class maps may provide valuable constraints for improved ab initio and template-based prediction of protein structures, naturally incorporate multiple templates, and yield state-of-the-art binary maps. Predictions of protein structures and 8 Å contact maps based on the multi-class distance map predictors described in this paper are freely available to academic users at the url http://distill.ucd.ie/. 相似文献319.
Bleesing JJ Souto-Carneiro MM Savage WJ Brown MR Martinez C Yavuz S Brenner S Siegel RM Horwitz ME Lipsky PE Malech HL Fleisher TA 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(11):7096-7103
In this study, we have identified an altered B cell compartment in patients with chronic granulomatous disease (CGD), a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH activity. This is characterized by an expansion of CD5-expressing B cells, and profound reduction in B cells expressing the memory B cell marker, CD27. Both findings were independent of the age, genotype, and clinical status of the patients, and were not accompanied by altered CD5 and CD27 expression on T cells. Focusing on CD27-positive B cells, considered to be memory cells based on somatically mutated Ig genes, we found that the reduction was not caused by CD27 shedding or abnormal retention of CD27 protein inside the cell. Rather, it was determined that CD27-negative B cells were, appropriately, CD27 mRNA negative, consistent with a naive phenotype, whereas CD27-positive B cells contained abundant CD27 mRNA and displayed somatic mutations, consistent with a memory B cell phenotype. Thus, it appears that CGD is associated with a significant reduction in the peripheral blood memory B cell compartment, but that the basic processes of somatic mutation and expression of CD27 are intact. X-linked carriers of CGD revealed a significant correlation between the percentage of CD27-positive B cells and the percentage of neutrophils with normal NADPH activity, reflective of the degree of X chromosome lyonization. These results suggest a role for NADPH in the process of memory B cell formation, inviting further exploration of secondary Ab responses in CGD patients. 相似文献
320.
Philippe GAC Vanden Bergh Thomas Fett Laurent LM Zecchinon Anne VT Thomas Daniel JM Desmecht 《BMC veterinary research》2005,1(1):1-7