共查询到20条相似文献,搜索用时 31 毫秒
1.
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.Methods
To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA.Results
All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 109/L and platelet counts greater than 20 × 109/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%.Conclusion
HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.2.
David M. Deery John B. Passioura Jason R. Condon Asitha Katupitiya 《Plant and Soil》2013,368(1-2):483-492
Aims
To determine soil water diffusivity, D(θ), on undisturbed field soil at medium to low water content (suction range from 10 to 150 m of water), for the purpose of modeling the uptake of water by plant roots.Methods
The method is based on the analysis of one-step outflow induced by a turbulent stream of dry air over the exposed end of a soil core, with the other end of the core enclosed. The outflow is measured through time as the change in the weight of the core as it sits on a recording balance. D(θ) is calculated by deconvoluting the measured outflow function.Results
Over the suction range of 10 to 150 m of water, D(θ) calculated on the undisturbed soil ranged from 20?×?10?9 to 10?×?10?9 [m2?s?1], substantially higher than other published estimates over this range in suction.Conclusions
These unusually large values cast doubt on the view that flow of water to roots limits uptake of water from the targeted subsoil. 相似文献3.
Growth and metabolism characteristics of anaerobic ammonium-oxidizing bacteria aggregates 总被引:1,自引:0,他引:1
Ting-Ting Chen Ping Zheng Li-Dong Shen 《Applied microbiology and biotechnology》2013,97(12):5575-5583
The present study reported the growth and metabolism characteristics of anaerobic ammonium-oxidizing (anammox) bacteria aggregates in an expanded granular sludge bed (EGSB). The results showed that the anammox bacteria aggregates presented starvation, growth, and inhibition phase along with the increase of substrate supply. The substrate conversion rates for survival were 0.05 kgNH 4 + –N/(kgVSS·day), 0.07 kgNO 2 ? –N/(kgVSS·day), and 0.12 kgN/(kgVSS·day); the substrate conversion rates for maximum growth were 0.21 kgNH 4 + –N/(kgVSS·day), 0.24 kgNH 4 + –N/(kgVSS·day), and 0.45 kgNH 4 + –N/(kgVSS·day), respectively. In the growth phase, the yield of anammox bacteria aggregates was 0.14 gVSS/(gNH 4 + –N), 0.12 gVSS/(gNO 2 ? –N), and 0.70 gVSS/(gNO 3 ? –N); the yield of extracellular polymeric substances (EPS) was 0.11 gEPS/(gNH 4 + –N), 0.09 gEPS/(gNO 2 ? –N), and 0.55 gEPS/(gNO 3 ? –N), respectively. The EPS contents in anammox bacteria aggregates were high compared to that in anaerobic granular sludge. Speculated from the cell yield, the energy for anammox bacteria growth was not only from nitrite oxidation, but also from anammox reaction. 相似文献
4.
Background
One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). Inflammatory regulators appear to be involved in the pathogenesis of BPD, possibly beginning in fetal life. To evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for determining risk of BPD, we conducted a cross-sectional study of infants born at less than 28 weeks of gestation (n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 of their peers who did not develop BPD.Results
Umbilical cord expression profiles at birth exhibited systematic differences in bioenergetic pathways with respect to gestational age. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, which have previously been implicated in several adult onset lung diseases. These findings are consistent with prior work on inflammatory processes and bioenergetics in prematurity.Conclusion
This study of gene expression of the newborn umbilical cord implicates the chromatin remodeling pathways in those premature infants who subsequently develop BPD. Larger sample sizes will be required to generate prognostic markers from umbilical cord profiles. 相似文献5.
Tânia L. Costa Everardo V. S. B. Sampaio Margareth F. Sales Luciano J. O. Accioly Tiago D. Althoff Frans G. C. Pareyn Eliza R. G. M. Albuquerque Rômulo S. C. Menezes 《Plant and Soil》2014,378(1-2):113-123
Aims
Root and shoot biomasses and their ratio (R:S) were determined for three stages of forest regeneration (18, 40 and >?60 years.), and for open and dense vegetation, in four soil classes in the semi-arid region of Northeast Brazil.Methods
Shoot biomasses were estimated by allometry and roots were collected in 0.7?×?0.7?×?1 m trenches.Results
Root and shoot biomasses and the R:S ratio were over double in the >60 year-old vegetation (R:S?=?0.67) when compared to more recent regenerated areas (0.32). In dense vegetation the biomass of roots and shoots were also more than the double of those in open vegetation but the R:S ratios were not significantly different (0.51 and 0.49). Litholic Neosols had lower ratio (0.22) than the other soil classes (0.53 to 0.63) and dense and open vegetation did not differ. In all areas except in deep sandy Quartzarenic Neosols most of the roots (> 90 %) were in the upper 40-cm layer of the soil profile, and consisted of coarse roots.Conclusion
Root biomass accumulates more slowly than aboveground biomass and it takes several decades to stabilize in shallower soils. The R:S ratios are higher when compared to other dry land forests, probably due to low water availability. 相似文献6.
Chanjuan Guo Judy Simon Rainer Gasche Pascale Sarah Naumann Carolin Bimüller Rodica Pena Andrea Polle Ingrid Kögel-Knabner Bernd Zeller Heinz Rennenberg Michael Dannenmann 《Plant and Soil》2013,369(1-2):657-668
Aims
Our aims were to characterize the fate of leaf-litter-derived nitrogen in the plant-soil-microbe system of a temperate beech forest of Southern Germany and to identify its importance for N nutrition of beech seedlings.Methods
15N-labelled leaf litter was traced in situ into abiotic and biotic N pools in mineral soil as well as into beech seedlings and mycorrhizal root tips over three growing seasons.Results
There was a rapid transfer of 15N into the mineral soil already 21 days after tracer application with soil microbial biomass initially representing the dominant litter-N sink. However, 15N recovery in non-extractable soil N pools strongly increased over time and subsequently became the dominant 15N sink. Recovery in plant biomass accounted for only 0.025 % of 15N excess after 876 days. After three growing seasons, 15N excess recovery was characterized by the following sequence: non-extractable soil N?>>?extractable soil N including microbial biomass?>>?plant biomass?>?ectomycorrhizal root tips.Conclusions
After quick vertical dislocation and cycling through microbial N pools, there was a rapid stabilization of leaf-litter-derived N in non-extractable N pools of the mineral soil. Very low 15N recovery in beech seedlings suggests a high importance of other N sources such as root litter for N nutrition of beech understorey. 相似文献7.
Christina Halsey Georgina Buck Sue Richards Faraneh Vargha-Khadem Frank Hill Brenda Gibson 《Journal of hematology & oncology》2011,4(1):1-12
Background
The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n = 555) versus related controls (n = 311), (2) low-risk children (presenting white cell count (WCC) < 50 × 109/l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years) randomised to HDM (n = 79) versus cranial irradiation (n = 77).Results
There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P < 0.002) with a higher proportion of children with IQs < 80 in the patient groups (13% vs. 5% at 3 years p = 0.003).Conclusion
Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes.Trial registration
ISRCTN: ISRCTN16757172 相似文献8.
Yvan Wenger Dingsheng Li Olivier Jolliet 《The International Journal of Life Cycle Assessment》2012,17(7):919-931
Purpose
Life cycle assessment (LCA) has largely focused on characterizing the impact of outdoor emissions. However, the intake fraction (iF) of indoor air emissions could be more important. The present paper aims to determine the long-term intake fractions of indoor emissions, including multiple indoor removal pathways such as sorption on indoor surfaces, and to compare it to the outdoor intake fraction.Method
The developed model accounts for the different removal pathways in buildings, including air exchange, degradation in the gas phase, degradation on surfaces, and finally partitioning between air, walls, and furniture assuming a kinetically limited material transfer between gas phase and a near-surface film. The indoor intake fraction is presented as a function of the adsorption and degradation rate on surfaces.Results and discussion
The intake fraction of volatile substances is only affected by the ventilation rate, with a constant intake fraction of 1?×?10?2. For ozone-sensitive substances, indoor gas phase reactions can significantly reduce the intake fraction. Semi-volatile substances are affected by the adsorption and degradation on room surfaces. For highly adsorbing substances, the decrease in intake fraction is limited to a minimum value of 2.5?×?10?4 by the mass transfer rate between air and room surfaces for a typical office or residence room in developed countries with temperate climate. Indoor intake fraction is compared to outdoor intake fraction calculated using the Impact 2002 multimedia model. Typical calculated indoor intake fraction values are in a significantly higher range (2.5?×?10?4 to 1?×?10?2) than inhalation outdoor values (1?×?10?9 to 1?×?10?6).Conclusions
This paper opens new possibilities to assess the health impact of indoor and outdoor air emissions in a consistent way, including surface sorption??a major removal pathway for semi-volatile compounds. By combining the newly calculated intake fractions with effect factors and with indoor and outdoor emissions per functional unit, it becomes possible to consistently account for indoor exposure in methods such as LCA 相似文献9.
Dörte Randewig Domenica Hamisch Monika Eiblmeier Christian Boedecker Jürgen Kreuzwieser Ralf R. Mendel Robert Hänsch Cornelia Herschbach Heinz Rennenberg 《Trees - Structure and Function》2014,28(2):399-411
Key Message
The critical level for SO 2 susceptibility of Populus × canescens is approximately 1.2 μL L ?1 SO 2 . Both sulfite oxidation and sulfite reduction and assimilation contribute to SO 2 detoxification.Abstract
In the present study, uptake, susceptibility and metabolism of SO2 were analyzed in the deciduous tree species poplar (Populus × canescens). A particular focus was on the significance of sulfite oxidase (SO) for sulfite detoxification, as SO has been characterized as a safety valve for SO2 detoxification in herbaceous plants. For this purpose, poplar plants were exposed to different levels of SO2 (0.65, 0.8, 1.0, 1.2 μL L?1) and were characterized by visible injuries and at the physiological level. Gas exchange parameters (stomatal conductance for water vapor, CO2 assimilation, SO2 uptake) of the shoots were compared with metabolite levels (sulfate, thiols) and enzyme activities [SO, adenosine 5′-phosphosulfate reductase (APR)] in expanding leaves (80–90 % expanded). The critical dosage of SO2 that confers injury to the leaves was 1.2 μL L?1 SO2. The observed increase in sulfur containing compounds (sulfate and thiols) in the expanding leaves strongly correlated with total SO2 uptake of the plant shoot, whereas SO2 uptake rate was strongly correlated with stomatal conductance for water vapor. Furthermore, exposure to high concentration of SO2 revealed channeling of sulfite through assimilatory sulfate reduction that contributes in addition to SO-mediated sulfite oxidation to sulfite detoxification in expanding leaves of this woody plant species. 相似文献10.
Cornel Pater 《Trials》2004,5(1):1-7
Objectives
Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF).Materials and methods
We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF.Results
Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients.Conclusions
Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed. 相似文献11.
Seyed Mansoor Rayegani Elham Daneshtalab Mohamad Hasan Bahrami Dariush Eliaspour Seyed Ahmad Raeissadat Sajjad Rezaei Marzieh Babaee 《Journal of brachial plexus and peripheral nerve injury》2011,6(1):1-5
Background
Variations in the branching of posterior cord are important during surgical approaches to the axilla and upper arm, administration of anesthetic blocks, interpreting effects of nervous compressions and in repair of plexus injuries. The patterns of branching show population differences. Data from the African population is scarce.Objective
To describe the branching pattern of the posterior cord in a Kenyan population.Materials and methods
Seventy-five brachial plexuses from 68 formalin fixed cadavers were explored by gross dissection. Origin and order of branching of the posterior cord was recorded. Representative photographs were then taken using a digital camera (Sony Cybershot R, W200, 7.2 Megapixels).Results
Only 8 out of 75 (10.7%) posterior cords showed the classical branching pattern. Forty three (57.3%) lower subscapular, 8(10.3%) thoracodorsal and 8(10.3%) upper subscapular nerves came from the axillary nerve instead of directly from posterior cord. A new finding was that in 4(5.3%) and in 3(4%) the medial cutaneous nerves of the arm and forearm respectively originated from the posterior cord in contrast to their usual origin from the medial cord.Conclusions
Majority of posterior cords in studied population display a wide range of variations. Anesthesiologists administering local anesthetic blocks, clinicians interpreting effects of nerve injuries of the upper limb and surgeons operating in the axilla should be aware of these patterns to avoid inadvertent injury. A wider study of the branching pattern of infraclavicular brachial plexus is recommended. 相似文献12.
Robert CG Martin Ken Robbins Dana Tomalty Ryan O'Hara Petar Bosnjakovic Radek Padr Miloslav Rocek Frantisek Slauf Alexander Scupchenko Cliff Tatum 《World journal of surgical oncology》2009,7(1):1-12
Background
Following failure of standard systemic chemotherapy, the role of hepatic transarterial therapy for colorectal hepatic metastasis continues to evolve as the experience with this technique matures. The aim of this study to gain a better understanding of the value of drug eluting bead therapy when administered to patients with unresectable colorectal hepatic metastasis.Methods
This was an open-label, multi-center, single arm study, of unresectable colorectal hepatic metastasis patients who had failed standard therapy from 10/2006-10/2008. Patients received repeat embolizations with Irinotecan loaded beads(max 100 mg per embolization) per treating physician's discretion.Results
Fifty-five patients underwent 99 treatments using Irinotecan drug eluting beads. The median number of total treatments per patient was 2(range of 1-5). Median length of hospital stay was 23 hours(range 23 hours - 10 days). There were 30(30%) sessions associated with adverse reactions during or after the treatment. The median disease free and overall survival from the time of first treatment was 247 days and 343 days. Six patients(10%) were downstaged from their original disease status. Of these, four were treated with surgery and two with RFA. Neither number of liver lesions, size of liver lesions or extent of liver replacement(<= 25% vs >25%) were predictors of overall survival. Only the presence of extrahepatic disease(p = 0,001), extent of prior chemotherapy (failed 1st and 2nd line vs > 2 line failure)(p = 0,007) were predictors of overall survival in multivariate analysis.Conclusion
Chemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response. 相似文献13.
Guzin Akkuzu Babur Akkuzu Erdinc Aydin Murat Derbent Levent Ozluoglu 《Journal of medical case reports》2007,1(1):1-3
Purpose
To describe the development of presumed immune-mediated stromal rejection after automated lamellar therapeutic keratoplasty (ALTK) and its reversal after initiation of intensive topical corticosteroid therapy.Methods
Observational case report.Results
Stromal edema localized in the graft developed 42 days after ALTK for Avellino corneal dystrophy in a 65-year-old man. After one week of intensive topical corticosteroids, complete reversal of graft edema occurred, with full recovery of visual function.Conclusion
The clinical appearance and response to therapy in this case supported the diagnosis of immune-mediated stromal rejection. Ophthalmologists should be aware that stromal rejection may occur in lamellar corneal grafts. 相似文献14.
Huajiang Chen Jianxi Wang Bo Hu Xiaodong Wu Yu Chen Renhu Li Wen Yuan 《Molecular and cellular biochemistry》2015,398(1-2):21-30
Seven organorhenium pentylcarbonate compounds (PC1–PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 104, 3.9 × 104, and 4.2 × 104 M?1, respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly. 相似文献
15.
Agne Babusyte Kristina Stravinskaite Jolanta Jeroch Jan Lötvall Raimundas Sakalauskas Brigita Sitkauskiene 《Respiratory research》2007,8(1):81-9
Background
Smoking activates and recruits inflammatory cells and proteases to the airways. Matrix metalloproteinase (MMP)-12 may be a key mediator in smoke induced emphysema. However, the influence of smoking and its cessation on airway inflammation and MMP-12 expression during COPD is still unknown. We aimed to analyse airway inflammatory cell patterns in induced sputum (IS) and bronchoalveolar lavage (BAL) from COPD patients who are active smokers and who have ceased smoking >2 years ago.Methods
39 COPD outpatients – smokers (n = 22) and ex-smokers (n = 17) were studied. 8 'healthy' smokers and 11 healthy never-smokers were tested as the control groups. IS and BAL samples were obtained for differential and MMP-12+-macrophages count analysis.Results
The number of IS neutrophils was higher in both COPD groups compared to both controls. The amount of BAL neutrophils was higher in COPD smokers compared to healthy never-smokers. The number of BAL MMP-12+-macrophages was higher in COPD smokers (1.6 ± 0.3 × 106/ml) compared to COPD ex-smokers, 'healthy' smokers and healthy never-smokers (0.9 ± 0.4, 0.4 ± 0.2, 0.2 ± 0.1 × 106/ml respectively, p < 0.05).Conclusion
The lower amount of BAL neutrophils in COPD ex-smokers, compared to COPD smokers, suggests positive alterations in alveolar compartment after smoking cessation. Smoking and disease itself may stimulate MMP-12 expression in airway compartments (IS and BAL) from COPD patients. 相似文献16.
Key message
The gene and cDNA sequence encoding PAL from Chinese medicinal plant Rhus chinensis were cloned and analyzed, furthermore the biochemical properties, kinetic parameters, differential expression and key sites were studied.Abstract
Rhus chinensis is a well-known Chinese medicinal plant. Phenylalanine ammonia-lyase (PAL) is the first enzyme of phenylpropanoid pathway. Several recent studies suggested that PAL also play an important role in plant–aphid interaction. In this study, both the cDNA and the genomic sequence encoding PAL from Rhus chinensis (designated as RcPAL) were cloned and analyzed. The 3,833 bp gene contained a 1,342 bp intron and two extrons. The ORF was 2,124 bp and predicted to encode a 707-amino acid polypeptide. The results of real-time PCR showed that RcPAL expressed in all tested tissues and followed the order: stems > young leaves > petioles > roots > seeds > mature leaves. RcPAL was successfully expressed in E. coli with the pET-28a-RcPAL recombinant vector. The recombinant protein exhibited a high level of PAL activity. Biochemical properties and kinetic parameters of recombinant RcPAL were further studied. The results showed that the optimal temperature and pH for RcPAL activity were 45 °C and 9.0, and the K m and K cat values were 7.90 mM and 52.31 s?1, respectively. The active sites and substrate selectivity site were also investigated with site-directed mutagenesis methods, suggesting that Phe126 is responsible for the substrate selectivity. To our knowledge, this was the first full-length PAL gene cloned and characterized from the family Anacardiaceae so far. 相似文献17.
Rafik Karaman Ghadeer Dokmak Maryam Bader Hussein Hallak Mustafa Khamis Laura Scrano Sabino Aurelio Bufo 《Journal of molecular modeling》2013,19(1):439-452
Density functional theory (DFT) calculations at B3LYP/6-31 G (d,p) and B3LYP/6-311?+?G(d,p) levels for the substituted pyridine-catalyzed isomerization of monomethyl maleate revealed that isomerization proceeds via four steps, with the rate-limiting step being proton transfer from the substituted pyridinium ion to the C=C double bond in INT1. In addition, it was found that the isomerization rate (maleate to fumarate) is solvent dependent. Polar solvents, such as water, tend to accelerate the isomerization rate, whereas apolar solvents, such as chloroform, act to slow down the reaction. A linear correlation was obtained between the isomerization activation energy and the dielectric constant of the solvent. Furthermore, linearity was achieved when the activation energy was plotted against the pK a value of the catalyst. Substituted-pyridine derivatives with high pK a values were able to catalyze isomerization more efficiently than those with low pK a values. The calculated relative rates for prodrugs 1–6 were: 1 (406.7), 2 (7.6?×?106), 3 (1.0), 4 (20.7), 5 (13.5) and 6 (2.2?×?103). This result indicates that isomerizations of prodrugs 1 and 3–5 are expected to be slow and that of prodrugs 2 and 6 are expected to be relatively fast. Hence, prodrugs 2 and 3–5 have the potential to be utilized as prodrugs for the slow release of monomethylfumarate in the treatment of psoriasis and multiple sclerosis. Figure
Substituted pyridine-catalyzed isomerization of monomethylmaleate (prodrug, cis-isomer) to monomethylfumerate (parental drug, trans-isomer) 相似文献
18.
Yiping Fei Ryan Webb Beth L Cobb Haner Direskeneli Güher Saruhan-Direskeneli Amr H Sawalha 《Arthritis research & therapy》2009,11(3):R66-7
Introduction
Behçet's disease is a chronic systemic inflammatory disease that remains incompletely understood. Herein, we perform the first genome-wide association study in Behçet's disease.Methods
Using DNA pooling technology and the Affymetrix 500K arrays, we identified possible candidate gene associations with Behçet's disease in a cohort of 152 Behçet's disease patients and 172 healthy ethnically matched controls. Genetic loci that were identified in the pooling study were genotyped in patients and controls using TaqMan genotyping technology.Results
We identified genetic associations between Behçet's disease and single-nucleotide polymorphisms (SNPs) in KIAA1529, CPVL, LOC100129342, UBASH3B, and UBAC2 (odds ratio = 2.04, 2.26, 1.84, 1.71, and 1.61, respectively; P value = 4.2 × 10-5, 1.0 × 10-4, 3.0 × 10-4, 1.5 × 10-3, and 5.8 × 10-3, respectively). Among the associated SNPs, the Behçet's disease-risk allele in rs2061634 leads to substitution of serine to cysteine at amino acid position 995 (S995C) in the KIAA1529 protein.Conclusions
Using an unbiased whole-genome genetic association approach, we identified novel candidate genetic loci that are associated with increased susceptibility for Behçet's disease. These findings will help to better understand the pathogenesis of Behçet's disease and identify novel targets for therapeutic intervention. 相似文献19.
Whiteside TL Butterfield LH Naylor PH Egan JE Hadden JW Baltzer L Wolf GT Berinstein NL 《Cancer immunology, immunotherapy : CII》2012,61(6):783-788
Objective
IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10?days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, peripheral blood lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2.Methods
Absolute lymphocyte numbers were determined in whole blood using the TetraONE System. Lymphocytes were further separated on Ficoll—Hypaque gradients and evaluated by multiparameter flow cytometry. Lymphocyte numbers, including regulatory T cells (Treg) and na?ve, memory and effector T cells, were compared in pre- and post-therapy specimens.Results
Total lymphocyte numbers remained unchanged after IRX-2 therapy. Significant changes occurred in numbers of circulating B cells and NKT cells, which decreased following IRX-2 therapy. The frequency of circulating Treg (CD4+CD25high) remained unaltered (e.g., 6.7?±?0.6% vs. 7.5?±?0.8%; means?±?SEM) as was the CD8+/Treg ratio (6.6 before and 6.7 after IRX-2 therapy). The mean absolute number of CD3+CD45RA+CCR7+ (na?ve) T cells was decreased after IRX-2 therapy but numbers of total memory (i.e., central and peripheral) and terminally differentiated T cells were unchanged.Conclusions
IRX-2-mediated reductions in B and NKT cell numbers in the blood suggest a redistribution of these cells to tissues. A decrease in na?ve T cells implies their up-regulated differentiation to memory T cells. Unchanged Treg numbers after IRX-2 therapy indicate that IRX-2 does not expand this compartment, potentially benefiting anti-tumor immune responses. 相似文献20.
Rachel A Collins Rosa C Gualano Graeme R Zosky Constance L Atkins Debra J Turner Giuseppe N Colasurdo Peter D Sly 《Respiratory research》2005,6(1):1-18