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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
Introduction
Autoantibodies to the Th/To antigen have been described in systemic sclerosis (SSc) and several proteins of the macromolecular Th/To complex have been reported to react with anti-Th/To antibodies. However, anti-Th/To has not been clinically utilized due to unavailability of commercial tests. The objective of the present study is to evaluate the newly developed ELISA and chemiluminescent immunoassay (CLIA) to measure autoantibodies to Rpp25 (a component of the Th/To complex) using immunoprecipitation (IP) as the reference method.Methods
The first cohort consisted of 123 SSc patients including 7 anti-Th/To positive samples confirmed by IP. Additional seven anti-Th/To positive samples from non-SSc patients were also tested. For evaluation of the QUANTA Flash Rpp25 CLIA (research use only), 8 anti-Th/To IP positives, a cohort of 70 unselected SSc patients and sera from various disease controls (n = 357) and random healthy individuals (n = 10) were studied.Results
Anti-Rpp25 antibodies determined by ELISA were found in 11/14 anti-Th/To IP positive but only in 1/156 (0.6%) negative samples resulting in a positive percent agreement of 78.6% (95% confidence interval [CI] 49.2, 95.3%) and a negative percent agreement of 99.4% (95% CI 96.4, 100.0%). To verify the results using a second method, 53 samples were tested by ELISA and CLIA for anti-Rpp25 reactivity and the results were highly correlated (rho = 0.71, 95% CI 0.56, 0.81; P < 0.0001). To define the cutoff of the CLIA, anti-Th/To IP positive and negative sera were tested using the anti-Rpp25 CLIA. At the cutoff selected by receiver operating characteristic (ROC) analysis 8/8 (100.0%) of the anti-Th/To positive sera but only 2/367 (0.5%) of the controls were positive for anti-Rpp25 antibodies. The positive and negative percent agreements were 100.0% (95% CI 63.1, 100.0%) and 99.5% (95% CI 98.0, 99.9%), respectively. In the disease cohorts 2/70 (2.9%) of the SSc patients were positive for anti-Rpp25 antibodies compared to 2/367 (0.5%) of the controls (P = 0.032). ROC analysis showed discrimination between SSc patients and controls with an area under the curve value of 0.732 (95% CI 0.655, 0.809).Conclusion
Rpp25 is a major target of autoantibodies to the Th/To autoantigen complex. Further studies are needed to evaluate the clinical utility of the new assays. 相似文献22.
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赖氨酰氧化酶(lysyl oxidases,LOXs)是一种能够催化细胞外基质蛋白(如胶原和弹性蛋白)交叉连接的酶类,这一功能使其在组织的稳定、重塑和伤口愈合中发挥重要作用.随着研究的不断深入,LOXs在细胞增殖、细胞趋化以及肿瘤发生等过程中也彰显出十分关键的作用.研究发现,一些诸如结缔组织病、剥脱综合症、铜代谢障碍性疾病及盆腔器官脱垂和骨疾等疾病的发生与LOXs有很大关系.综述了LOXs的生物合成、结构特点、多功能性以及与人类疾病的关系. 相似文献
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Okechukwu S Ogah Gail D Adegbite Rufus O Akinyemi Julius O Adesina Albert A Alabi Oscar I Udofia Roseline F Ogundipe Julius KL Osinfade 《BMC research notes》2008,1(1):1-10
Background
The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB) genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C), along with the genomes of laboratory strains (H37Rv and H37Ra), provides new insights on the mechanisms of adaptation of this bacterium to the human host.Findings
The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms.Conclusion
The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium. 相似文献26.
TOSHIHIRO TOKIWA DAVID MODRÝ AKIRA ITO KATEŘINA POMAJBÍKOVÁ KLÁRA J. PETRŽELKOVÁ SOICHI IMAI 《The Journal of eukaryotic microbiology》2010,57(2):115-120
ABSTRACT. Troglocorys cava n. g., n. sp. is described from the feces of wild eastern chimpanzee, Pan troglodytes schweinfurthii, in Uganda. This new species has a spherical body with a frontal lobe, a long vestibulum, a cytoproct located at the posterior dorsal side of the body, an ovoid macronucleus, a contractile vacuole near the cytoproct, and a large concavity on the left surface of the body. Buccal ciliature is non‐retractable and consists of three ciliary zones: an adoral zone surrounding the vestibular opening, a dorso‐adoral zone extending transversely at the basis of the frontal lobe, and a vestibular zone longitudinally extending in a gently spiral curve to line the surface of the vestibulum. Two non‐retractable somatic ciliary zones comprise arches over the body surface: a short dorsal ciliary arch extending transversely at the basis of the frontal lobe and a wide C‐shaped left ciliary arch in the left concavity. Because of the presence of three ciliary zones in the non‐retractable buccal ciliature, the present genus might be a member of the family Blepharocorythidae, but the large left concavity and the C‐shaped left ciliary arch are unique, such structures have never been described from other blepharocorythids. 相似文献
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Angela Ceribelli Micaela Fredi Mara Taraborelli Ilaria Cavazzana Franco Franceschini Marzia Quinzanini Angela Tincani Steven J Ross Jason YF Chan Brad A Pauley Edward KL Chan Minoru Satoh 《Arthritis research & therapy》2012,14(2):1-6
Introduction
Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults.Methods
By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression.Results
SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 ??M (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 ??M among those with GFR ?? 60 versus < 60 ml/min per 1.73 m2, respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05).Conclusions
These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level. 相似文献29.
Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma. 相似文献
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Smirnova I Poltorak A Chan EK McBride C Beutler B 《Genome biology》2000,1(1):research002.1-research00210