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52.
Geraint B Rogers Leah Cuthbertson Lucas R Hoffman Peter AC Wing Christopher Pope Danny A P Hooftman Andrew K Lilley Anna Oliver Mary P Carroll Kenneth D Bruce Christopher J van der Gast 《The ISME journal》2013,7(4):697-706
High-throughput pyrosequencing and quantitative PCR (Q-PCR) analysis offer greatly improved accuracy and depth of characterisation of lower respiratory infections. However, such approaches suffer from an inability to distinguish between DNA derived from viable and non-viable bacteria. This discrimination represents an important step in characterising microbial communities, particularly in contexts with poor clearance of material or high antimicrobial stress, as non-viable bacteria and extracellular DNA can contribute significantly to analyses. Pre-treatment of samples with propidium monoazide (PMA) is an effective approach to non-viable cell exclusion (NVCE). However, the impact of NVCE on microbial community characteristics (abundance, diversity, composition and structure) is not known. Here, adult cystic fibrosis (CF) sputum samples were used as a paradigm. The effects of PMA treatment on CF sputum bacterial community characteristics, as analysed by pyrosequencing and enumeration by species-specific (Pseudomonas aeruginosa) and total bacterial Q-PCR, were assessed. At the local community level, abundances of both total bacteria and of P. aeruginosa were significantly lower in PMA-treated sample portions. Meta-analysis indicated no overall significant differences in diversity; however, PMA treatment resulted in a significant alteration in local community membership in all cases. In contrast, at the metacommunity level, PMA treatment resulted in an increase in community evenness, driven by an increase in diversity, predominately representing rare community members. Importantly, PMA treatment facilitated the detection of both recognised and emerging CF pathogens, significantly influencing ‘core'' and ‘satellite'' taxa group membership. Our findings suggest failure to implement NVCE may result in skewed bacterial community analyses. 相似文献
53.
Christophe Rodriguez Cathia Soulié Anne-Geneviève Marcelin Vincent Calvez Diane Descamps Charlotte Charpentier Philippe Flandre Patricia Recordon-Pinson Pantxika Bellecave Jean-Michel Pawlotsky Bernard Masquelier the ANRS AC Study Group 《PloS one》2015,10(6)
Background
Maraviroc is an HIV entry inhibitor that alters the conformation of CCR5 and is poorly efficient in patients infected by viruses that use CXCR4 as an entry coreceptor. The goal of this study was to assess the capacity of ultra-deep pyrosequencing (UDPS) and different data analysis approaches to characterize HIV tropism at baseline and predict the therapeutic outcome on maraviroc treatment.Methods
113 patients with detectable HIV-1 RNA on HAART were treated with maraviroc. The virological response was assessed at months 1, 3 and 6. The sequence of the HIV V3 loop was determined at baseline and prediction of maraviroc response by different software and interpretation algorithms was analyzed.Results
UDPS followed by analysis with the Pyrotrop software or geno2pheno algorithm provided better prediction of the response to maraviroc than Sanger sequencing. We also found that the H34Y/S substitution in the V3 loop was the strongest individual predictor of maraviroc response, stronger than substitutions at positions 11 or 25 classically used in interpretation algorithms.Conclusions
UDPS is a powerful tool that can be used with confidence to predict maraviroc response in HIV-1-infected patients. Improvement of the predictive value of interpretation algorithms is possible and our results suggest that adding the H34S/Y substitution would substantially improve the performance of the 11/25/charge rule. 相似文献54.
Denusa M Veríssimo Renata FC Leit?o S?nia D Figueiró Júlio C Góes Vilma Lima Charles O Silveira Gerly AC Brito 《Experimental biology and medicine (Maywood, N.J.)》2015,240(2):175-184
The aim of this study was to evaluate the bone regenerative effect of glutaraldehyde (GA) cross-linking on mineralized polyanionic collagen membranes in critical-sized defects on rat calvarias. Bone calvarial defects were induced in Wistar rats, which were then divided into five groups: a sham group; a control group, which received a commercial membrane; and GA, 25GA, and 75GA groups, which received one of three different polyanionic collagen membranes mineralized by 0, 25, or 75 hydroxyapatite cycles and then cross-linked by GA. Bone formation was evaluated based on digital radiography and computerized tomography. Histological analyses were performed 4 and 12 weeks after the surgical procedure to observe bone formation, membrane resorption, and fibrous tissue surrounding the membranes. Measurement of myeloperoxidase activity, tumor necrosis factor alpha, and interleukin 1beta production was performed 24 h after surgery. The percentage of new bone formation in the GA, 25GA, and 75GA groups was higher compared with the control and sham groups. In the GA and 25 GA groups, the membranes were still in place and were contained in a thick fibrous capsule after 12 weeks. No significant difference was found among the groups regarding myeloperoxidase activity and interleukin 1beta levels, although the GA, 25GA, and 75GA groups presented decreased levels of tumor necrosis factor alpha compared with the control group. These new GA cross-linked membranes accelerated bone healing of the calvarium defects and did not induce inflammation. In addition, unlike the control membrane, the experimental membranes were not absorbed during the analyzed period, so they may offer advantages in large bone defects where prolonged membrane barrier functions are desirable. 相似文献
55.
Overbeek MJ Boonstra A Voskuyl AE Vonk MC Vonk-Noordegraaf A van Berkel MP Mooi WJ Dijkmans BA Hondema LS Smit EF Grünberg K 《Arthritis research & therapy》2011,13(2):R61-13
Introduction
Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation.Methods
Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity.Results
All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals.Conclusions
PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity pattern is not paralleled by pPDGFR-β or PDGF-B patterns. PDGFR-β- and EGFR-immunoreactivity of pulmonary vessels distinguishes PAH patients from controls. 相似文献56.
Hennie G Raterman Alexandre E Voskuyl Ben AC Dijkmans Michael T Nurmohamed 《Arthritis research & therapy》2009,11(5):413-2
With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels.Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRÉ investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353).The prevalences of MetS were 35% and 25% (Table (Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table (Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60).
Open in a separate windowaMetabolic syndrome (MetS) according to National Cholesterol Education Program (NCEP) 2001; bMetS according to NCEP 2004. Continuous variables are presented as means (± standard deviations) in cases of normal distribution or as medians (interquartile ranges) in cases of non-normal distribution. BMI, body mass index; CRP, C-reactive protein; DAS28, disease activity score using 28 joint counts; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; HCQ, hydroxychloroquine; MTX, methotrexate; RA, rheumatoid arthritis; SSZ, sulfasalazine; TNF, tumour necrosis factor.
Open in a separate windowaIn multivariate analyses, the following variables were used: gender, age, prednisolone only, methotrexate only, sulfasalazine only, hydroxychloroquine only, tumour necrosis factor-blocking agents, combination of disease-modifying antirheumatic drugs, pack-years, smoking, erosions, DAS28 (disease activity score using 28 joint counts), body mass index, pulse rate, creatinine levels, renal clearance, hypothyroidism and diabetes mellitus. CI, confidence interval; OR, odds ratio.Therefore, to get more support for a drug-specific effect, it is of interest to know whether or not in the study of Toms and colleagues the MTX effect was present only in the group of RA patients with single use of MTX or in the group of MTX-treated patients with other antirheumatic drugs. As patients with MetS were significantly older, it would give further information whether age was an independent risk factor for MetS in regression analyses. Moreover, as readers, we are not informed about comorbidities like diabetes and clinical hypothyroidism, which are notorious cardiometabolic risk factors. On the whole, we could not confirm a plausible protective role for the use of MTX and presence of MetS, and hence further investigation is required to explain the discrepancy between our findings and those of Toms and colleagues. 相似文献
Table 1
Characteristics of the study populationMetS presenta | MetS absenta | MetS presentb | MetS absentb | |||
---|---|---|---|---|---|---|
n = 84 | n = 265 | n = 121 | n = 228 | P valuea | P valueb | |
Demographics | ||||||
Age, years | 63.8 (± 8) | 63.1 (± 7) | 64.3 (± 8) | 62.7 (± 7) | 0.46 | 0.045 |
Female, percentage | 76 | 63 | 74 | 62 | 0.022 | 0.028 |
RA-related characteristics | ||||||
DAS28 | 4.2 (± 1.3) | 3.9 (± 1.4) | 4.1 (± 1.3) | 3.8 (± 1.4) | 0.21 | 0.062 |
ESR, mm/hour | 22 (10-35) | 16 (9-30) | 20 (10-34) | 17 (9-31) | 0.059 | 0.33 |
CRP, mg/L | 11 (4-21) | 6 (3-16) | 8 (3-18) | 6 (3-19) | 0.021 | 0.46 |
RA duration, years | 7 (4-10) | 7 (4-10) | 7 (4-10) | 7 (5-10) | 0.83 | 0.19 |
Erosion, percentage | 77 | 83 | 79 | 83 | 0.20 | 0.36 |
Number of DMARDs | 1 (1-2) | 1 (1-1) | 1 (1-2) | 1 (1-1) | 0.26 | 0.43 |
MTX current, percentage | 62 | 60 | 63 | 59 | 0.71 | 0.46 |
MTX only, percentage | 39 | 39 | 41 | 38 | 0.95 | 0.67 |
SSZ only, percentage | 8 | 13 | 9 | 14 | 0.23 | 0.22 |
HCQ only, percentage | 1 | 4 | 3 | 4 | 0.31 | 0.55 |
Combination of DMARDs, percentage | 31 | 25 | 29 | 25 | 0.24 | 0.38 |
TNF-blocking agent, percentage | 11 | 9 | 11 | 9 | 0.73 | 0.65 |
Prednisolone only, percentage | 1 | 2 | 3 | 1 | 1.00 | 0.42 |
Cardiovascular risk factors | ||||||
Current smoker, percentage | 26 | 31 | 25 | 32 | 0.42 | 0.15 |
Pack-years, years | 17 (0-34) | 19 (2-38) | 19 (0-35) | 18 (2-38) | 0.23 | 0.75 |
BMI, kg/m2 | 30 (± 4) | 26 (± 5) | 29 (± 4) | 25 (± 5) | < 0.001 | < 0.001 |
Creatinine, μmol/L | 89 (± 21) | 89 (± 16) | 91 (± 22) | 87 (± 14) | 0.99 | 0.070 |
Renal clearance, mL/minute | 81 (± 24) | 72 (± 19) | 77 (± 23) | 73 (± 19) | 0.003 | 0.062 |
Pulse, beats per minute | 76 (± 11) | 73 (± 9) | 75 (± 11) | 73 (± 9) | 0.005 | 0.015 |
Diabetes mellitus, percentage | 14 | 3 | 12 | 3 | < 0.001 | 0.001 |
Hypothyroidism, percentage | 12 | 2 | 9 | 2 | 0.001 | 0.003 |
Table 2
Variables associated with metabolic syndromeUnivariate | Multivariatea | |||||
---|---|---|---|---|---|---|
OR | 95% CI | P value | OR | 95% CI | P value | |
Body mass index | 1.2 | 1.1-1.3 | < 0.001 | 1.2 | 1.1-1.3 | < 0.001 |
Pulse | 1.03 | 1.01-1.06 | 0.011 | 1.03 | 1.00-1.06 | 0.020 |
Creatinine | 1.01 | 1.00-1.02 | 0.080 | 1.02 | 1.00-1.03 | 0.017 |
Hypothyroidism | 4.5 | 1.5-13.2 | 0.007 | 4.7 | 1.5-15.0 | 0.009 |
Diabetes mellitus | 4.8 | 1.8-12.9 | 0.002 | 4.5 | 1.4-15.2 | 0.014 |
57.
Jennie Ursum Wouter H Bos Rob J van de Stadt Ben AC Dijkmans Dirkjan van Schaardenburg 《Arthritis research & therapy》2009,11(3):R75-6
Introduction
The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic. 相似文献58.
This report describes a lysozyme expressed at high levels in the stomach of
the hoatzin, the only known foregut-fermenting bird. Evolutionary
comparison places it among the calcium-binding lysozymes rather than among
the conventional types. Conventional lysozymes were recruited as digestive
enzymes twice in the evolution of mammalian foregut fermenters, and these
independently recruited lysozymes share convergent structural changes
attributed to selective pressures in the stomach. Biochemical convergence
and parallel amino acid replacements are observed in the hoatzin stomach
lysozyme even though it has a different genetic origin from the mammalian
examples and has undergone more than 300 million years of independent
evolution.
相似文献
59.
Astringency of aqueous solutions of phenolic compounds (grape seed tannins,
tannic acid, catechin and gallic acid) increased upon addition of citric
acid, whereas the astringency of alum was reduced. Astringency of alum was
decreased equivalently by addition of equi-sour levels of lactic acid,
citric acid or hydrochloric acid. The difference between alum and the
phenolic compounds is speculated to result from chemical modifications
affecting binding of the astringents with oral proteins rather than
cognitive differences. Chelation of the aluminum ion in alum by acids
reduces its availability for interacting with salivary proteins or
epithelial proteins. In contrast, the increased astringency produced upon
acidification of phenolic compounds is speculated to result from the pH
driven increase in the affinity of the phenols for binding with proteins.
These results suggest that alum cannot be used interchangeably with
phenolic astringents in psychophysical studies.
相似文献
60.