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71.
Sarita AY Hartgring Cynthia R Willis Johannes WJ Bijlsma Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2012,14(3):R137
Introduction
We sought to investigate the capacity of interleukin (IL)-7 to enhance collagen-induced arthritis and to study by what mechanisms this is achieved.Methods
Mice received multiple injections with IL-7 or phosphate-buffered saline (PBS) as a control. Arthritis severity and incidence were determined by visual examination of the paws. Joint destruction was determined by assessing radiographs and immunohistochemistry of the ankle joints. Total cellularity and numbers of T-cell and B-cell subsets were assessed, as well as ex vivo production of interferon-γ (IFN-γ), IL-17, and IL-4. Proinflammatory mediators were measured in serum with multianalyte profiling.Results
IL-7 increased arthritis severity and radiology-assessed joint destruction. This was consistent with IL-7-increased intensity of cell infiltrates, bone erosions, and cartilage damage. Splenic CD19+ B cells and CD19+/GL7+ germinal center B cells, as well as CD4 and CD8 numbers, were increased by IL-7. IL-7 expanded memory T cells, associated with increased percentages of IFN-γ-, IL-4-, and IL-17-producing CD4+ T cells. On antigen restimulation of draining lymph node cells in vitro IL-7 treatment was found to increase IFN-γ and IL-17 production, whereas IL-4 was reduced. IL-7 also increased concentrations of proinflammatory mediators, indicative of T-cell activation (sCD40L), vascular activation (VCAM-1, VEGF), tissue destruction (fibroblast growth factor-basic (FGF-b), LIF), and chemotaxis (MIP-1γ, MIP-3β, lymphotactin, MDC, and MCP-5).Conclusions
In arthritic mice, IL-7 causes expansion of T and B cells, associated with increased levels of proinflammatory mediators. IL-7 intensifies arthritis severity and joint destruction, accompanied by increased Th1 and Th17 activity. These data indicate that IL-7 could be an important mediator in arthritic conditions and that targeting IL-7 or its receptor represent novel therapeutic strategies. 相似文献72.
Iridovirus and microsporidian linked to honey bee colony decline 总被引:1,自引:0,他引:1
Bromenshenk JJ Henderson CB Wick CH Stanford MF Zulich AW Jabbour RE Deshpande SV McCubbin PE Seccomb RA Welch PM Williams T Firth DR Skowronski E Lehmann MM Bilimoria SL Gress J Wanner KW Cramer RA 《PloS one》2010,5(10):e13181
Background
In 2010 Colony Collapse Disorder (CCD), again devastated honey bee colonies in the USA, indicating that the problem is neither diminishing nor has it been resolved. Many CCD investigations, using sensitive genome-based methods, have found small RNA bee viruses and the microsporidia, Nosema apis and N. ceranae in healthy and collapsing colonies alike with no single pathogen firmly linked to honey bee losses.Methodology/Principal Findings
We used Mass spectrometry-based proteomics (MSP) to identify and quantify thousands of proteins from healthy and collapsing bee colonies. MSP revealed two unreported RNA viruses in North American honey bees, Varroa destructor-1 virus and Kakugo virus, and identified an invertebrate iridescent virus (IIV) (Iridoviridae) associated with CCD colonies. Prevalence of IIV significantly discriminated among strong, failing, and collapsed colonies. In addition, bees in failing colonies contained not only IIV, but also Nosema. Co-occurrence of these microbes consistently marked CCD in (1) bees from commercial apiaries sampled across the U.S. in 2006–2007, (2) bees sequentially sampled as the disorder progressed in an observation hive colony in 2008, and (3) bees from a recurrence of CCD in Florida in 2009. The pathogen pairing was not observed in samples from colonies with no history of CCD, namely bees from Australia and a large, non-migratory beekeeping business in Montana. Laboratory cage trials with a strain of IIV type 6 and Nosema ceranae confirmed that co-infection with these two pathogens was more lethal to bees than either pathogen alone.Conclusions/Significance
These findings implicate co-infection by IIV and Nosema with honey bee colony decline, giving credence to older research pointing to IIV, interacting with Nosema and mites, as probable cause of bee losses in the USA, Europe, and Asia. We next need to characterize the IIV and Nosema that we detected and develop management practices to reduce honey bee losses. 相似文献73.
W. W. Parmley K. Chatterjee G. S. Francis B. G. Firth R. A. Kloner 《The Western journal of medicine》1991,154(4):427-441
Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome. 相似文献
74.
75.
A homologous family of UDP- N -acetylgalactosamine: polypeptide N -
acetylgalactosaminyltransferases (GalNAc-transferases) initiate O-
glycosylation. These transferases share overall amino acid sequence
similarities of approximately 45-50%, but segments with higher similarities
of approximately 80% are found in the putative catalytic domain. Here we
have characterized the genomic organization of the coding regions of three
GalNAc-transferase genes and determined their chromosomal localization. The
coding regions of GALNT1 , -T2 , and -T3 were found to span 11, 16, and 10
exons, respectively. Several intron/exon boundaries were conserved within
the three genes. One conserved boundary was shared in a homologous C.
elegans GalNAc- transferase gene. Fluorescence in situ hybridization showed
that GALNT1 , -T2 , and -T3 are localized at chromosomes 18q12-q21,
1q41-q42, and 2q24-q31, respectively. These results suggest that the
members of the polypeptide GalNAc-transferase family diverged early in
evolution from a common ancestral gene through gene duplication.
相似文献
76.
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78.
Bosco A McKenna KL Devitt CJ Firth MJ Sly PD Holt PG 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(8):4766-4777
Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen-specific T memory cells. However, clinical trials with recently developed Th2 inhibitors in atopics have proven disappointing, suggesting underlying complexities in atopy pathogenesis which are not satisfactorily explained via the classical Th1/Th2 paradigm. One likely possibility is that additional Th2-associated genes which are central to disease pathogenesis remain unidentified. The aim of the present study was to identify such novel Th2-associated genes in recall responses to the inhalant allergen house dust mite. In contrast to earlier human microarray studies in atopy which focused on mitogen-activated T cell lines and clones, we concentrated on PBMC-derived primary T cells stimulated under more physiological conditions of low dose allergen exposure. We screened initially for allergen-induced gene activation by microarray, and validated novel genes in independent panels of subjects by quantitative RT-PCR. Kinetic analysis of allergen responses in PBMC revealed an early wave of novel atopy-associated genes involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a later wave of genes encoding the classical Th2 effector cytokines. We further demonstrate that these novel activation-associated Th2 genes up-regulate in response to another atopy-associated physiological stimulus bacterial superantigen, but remain quiescent in nonphysiological responses in primary T cells or cell lines driven by potent mitogens, which may account for their failure to be detected in earlier microarray studies. 相似文献
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