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61.
van Lent PL Nabbe KC Blom AB Sloetjes A Holthuysen AE Kolls J Van De Loo FA Holland SM Van Den Berg WB 《Arthritis research & therapy》2005,7(4):R885-R895
In previous studies we have found that FcγRI determines chondrocyte death and matrix metalloproteinase (MMP)-mediated cartilage
destruction during IFN-γ-regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to FcγRI leads to the
prominent production of oxygen radicals. In the present study we investigated the contribution of NADPH-oxidase-driven oxygen
radicals to cartilage destruction by using p47phox-/- mice lacking a functional NADPH oxidase complex. Induction of a passive ICA in the knee joints of p47phox-/- mice resulted in a significant elevation of joint inflammation at day 3 when compared with wild-type (WT) controls as studied
by histology. However, when IFN-γ was overexpressed by injection of adenoviral IFN-γ in the knee joint before ICA induction,
a similar influx of inflammatory cells was found at days 3 and 7, comprising mainly macrophages in both mouse strains. Proteoglycan
depletion from the cartilage layers of the knee joints in both groups was similar at days 3 and 7. Aggrecan breakdown in cartilage
caused by MMPs was further studied by immunolocalisation of MMP-mediated neoepitopes (VDIPEN). VDIPEN expression in the cartilage
layers of arthritic knee joints was markedly lower (between 30 and 60%) in IFN-γ-stimulated arthritic p47phox-/- mice at day 7 than in WT controls, despite significant upregulation of mRNA levels of various MMPs such as MMP-3, MMP-9,
MMP-12 and MMP-13 in synovia and MMP-13 in cartilage layers as measured with quantitative RT-PCR. The latter observation suggests
that oxygen radicals are involved in the activation of latent MMPs. Chondrocyte death, determined as the percentage of empty
lacunae in articular cartilage, ranged between 20 and 60% at day 3 and between 30 and 80% at day 7 in WT mice, and was completely
blocked in p47phox-/- mice at both time points. FcγRI mRNA expression was significantly lower, and FcγRII and FcγRIII were higher, in p47phox-/- mice than in controls. NADPH-oxidase-driven oxygen radical production determines chondrocyte death and aggravates MMP-mediated
cartilage destruction during IFN-γ-stimulated IC-mediated arthritis. Upregulation of FcγRI by oxygen radicals may contribute
to cartilage destruction. 相似文献
62.
63.
TL Kieft EM Murphy DL Haldeman PS Amy BN Bjornstad EV McDonald DB Ringelberg DC White J Stair RP Griffiths TC Gsell WE Holben DR Boone 《Microbial ecology》1998,36(3):336-348
Abstract Two chronosequences of unsaturated, buried loess sediments, ranging in age from <10,000 years to >1 million years, were investigated to reconstruct patterns of microbial ecological succession that have occurred since sediment burial. The relative importance of microbial transport and survival to succession was inferred from sediment ages, porewater ages, patterns of abundance (measured by direct counts, counts of culturable cells, and total phospholipid fatty acids), activities (measured by radiotracer and enzyme assays), and community composition (measured by phospholipid fatty acid patterns and Biolog substrate usage). Core samples were collected at two sites 40 km apart in the Palouse region of eastern Washington State, near the towns of Washtucna and Winona. The Washtucna site was flooded multiple times during the Pleistocene by glacial outburst floods; the Winona site elevation is above flood stage. Sediments at the Washtucna site were collected from near surface to 14.9 m depth, where the sediment age was approximately 250 ka and the porewater age was 3700 years; sample intervals at the Winona site ranged from near surface to 38 m (sediment age: approximately 1 Ma; porewater age: 1200 years). Microbial abundance and activities declined with depth at both sites; however, even the deepest, oldest sediments showed evidence of viable microorganisms. Same-age sediments had equal quantities of microorganisms, but different community types. Differences in community makeup between the two sites can be attributed to differences in groundwater recharge and paleoflooding. Estimates of the microbial community age can be constrained by porewater and sediment ages. In the shallower sediments (<9 m at Washtucna, <12 m at Winona), the microbial communities are likely similar in age to the groundwater; thus, microbial succession has been influenced by recent transport of microorganisms from the surface. In the deeper sediments, the populations may be considerably older than the porewater ages, since microbial transport is severely restricted in unsaturated sediments. This is particularly true at the Winona site, which was never flooded. 相似文献
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65.
Oral tolerance induction is thought to depend on special antigen presenting cells in the gut. A new report in the previous issue of Arthritis Research & Therapy supports this idea by demonstrating that indoleamine 2,3-dioxygenase-expressing dendritic cells in Peyer's patches from orally tolerized mice suppress T-cell responses via the generation of CD4+CD25+ regulatory T cells. This finding provides novel input into the mechanisms of oral tolerance that could further facilitate its use for the treatment of autoimmunity and chronic inflammatory reactions. 相似文献
66.
67.
Background
The relatively recent introduction of a highly efficient mosquito vector and an avian pathogen (Plasmodium relictum) to an isolated island ecosystem with naïve, highly susceptible avian hosts provides a unique opportunity to investigate evolution of virulence in a natural system. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct impacts on virulence. Toward further understanding of how host-parasite and parasite-parasite relationships may impact virulence, this study characterizes within-host diversity of malaria parasite populations based on genetic analysis of the trap (thrombospondin-related anonymous protein) gene in isolates originating from Hawaii, Maui and Kauai Islands.Methods
A total of 397 clones were produced by nested PCR amplification and cloning of a 1664 bp fragment of the trap gene from two malarial isolates, K1 (Kauai) and KV115 (Hawaii) that have been used for experimental studies, and from additional isolates from wild birds on Kauai, Maui and Hawaii Islands. Diversity of clones was evaluated initially by RFLP-based screening, followed by complete sequencing of 33 selected clones.Results
RFLP analysis of trap revealed a minimum of 28 distinct RFLP haplotypes among the 397 clones from 18 birds. Multiple trap haplotypes were detected in every bird evaluated, with an average of 5.9 haplotypes per bird. Overall diversity did not differ between the experimental isolates, however, a greater number of unique haplotypes were detected in K1 than in KV115. We detected high levels of clonal diversity with clear delineation between isolates K1 and KV115 in a haplotype network. The patterns of within-host haplotype clustering are consistent with the possibility of a clonal genetic structure and rapid within-host mutation after infection.Conclusion
Avian malaria (P. relictum) and Avipoxvirus are the significant infectious diseases currently affecting the native Hawaiian avifauna. This study shows that clonal diversity of Hawaiian isolates of P. relictum is much higher than previously recognized. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct implications for host demographics, disease management strategies, and evolution of virulence. The results of this study indicate a widespread presence of multiple-genotype malaria infections with high clonal diversity in native birds of Hawaii, which when coupled with concurrent infection with Avipoxvirus, may significantly influence evolution of virulence.Reviewers
This article was reviewed by Joseph Schall (nominated by Laura Landweber), Daniel Jeffares (nominated by Anthony Poole) and Susan Perkins (nominated by Eugene Koonin).68.
Amiodarone (AM) is an effective anti-arrhythmic drug. We investigated the role of mast cells and macrophages on AM induced pulmonary fibrosis and the action of atorvastatin on this fibrosis. Rats were allocated into four groups; negative control (1), positive control (2), 30 mg/kg body weight/day AM (3) and AM + 10 mg/kg/day atorvastatin (4). Lungs were harvested and prepared for histology and immunohistochemistry. Hematoxylin and eosin stained sections of group 3 exhibited disorganized lung architecture. We found cellular debris in the lumen of both intrapulmonary bronchi and bronchioles with partial disruption of the thickened epithelial lining and mononuclear cellular infiltration into the lamina propria. We also observed thickening of the epithelial lining and the smooth muscle layer. Congested, dilated and thickened blood capillaries and thickened inter-alveolar septa were observed with mononuclear cellular infiltrates in the lung of group 3. Most alveoli were collapsed, but some dilated ones were detected. In some alveoli, type ?? pneumocytes were increased, while type I cells were decreased. We observed significant increases in the amount of collagen in the thickened inter-alveolar septa, around bronchioles and around blood capillaries in sections from group 3. We found a significant increase in mast cells and alveolar macrophages in group 3 compared to group 1. Mast cells and macrophages appear to play important roles in AM induced pulmonary fibrosis. Atorvastatin appears to attenuate this condition. 相似文献
69.
Background
Sixteen, spring-born, single suckled, castrated male calves of Limousin × Holstein-Friesian and Simmental × Holstein-Friesian dams respectively, were used to investigate the effect of weaning on total leukocyte and differential counts, neutrophil functional activity, lymphocyte immunophenotypes, and acute phase protein response. Calves grazed with their dams until the end of the grazing season when they were housed in a slatted floor shed. On the day of housing, calves were assigned to a treatment, (i) abruptly weaned (W: n = 8) or (ii) non-weaned (controls) (C: n = 8). Weaned calves were housed in pens without their dams, whereas non-weaned (control) calves were housed with their dams. Blood was collected on day -7, 0 (housing), 2, 7, and 14 to determine total leukocyte and differential counts and concentration of fibrinogen and haptoglobin. Lymphocyte immunophenotypes were characterised using selected surface antigens (CD4+, CD8+, WC1+ (γδ T cells), MHC Class II+ lymphocytes), and the functional activities of neutrophils (surface expression of L-selectin (CD62L), phagocytic and oxidative burst activity) were investigated using flow cytometry. 相似文献70.
Sara S Roscioni Loes EM Kistemaker Mark H Menzen Carolina RS Elzinga Reinoud Gosens Andrew J Halayko Herman Meurs Martina Schmidt 《Respiratory research》2009,10(1):1-17