Standing: Who Speaks for the Environment?

Standing: Who Speaks for the Environment

Consortium: An Action for the Wife

Consortium: An Action For The Wif

Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells

IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55−/− but not p75−/− mice. The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55−/− mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. Treatment of macrophages with rTNF also inhibited p40 production in vitro. These findings indicate that at least one of the ways in which TNF regulates Th1/Th17 responses in arthritis is by down-regulating the expression of p40. Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells

Intrathoracic subclavian artery aneurysm repair in the thoracic endovascular aortic repair era

ObjectiveIntrathoracic subclavian artery aneurysms (SAAs) are rare aneurysms that often occur in association with congenital aortic arch anomalies and/or concomitant thoracic aortic pathology. The advent of thoracic endovascular aortic repair (TEVAR) methods may complement or replace conventional open SAA repair. Herein, we describe our experience with SAA repair in the TEVAR era.MethodsA retrospective review was performed of all intrathoracic SAAs repaired at a single institution since United States Food and Drug Administration approval of TEVAR in 2005.ResultsNineteen patients underwent 20 operations to repair 22 (13 native, nine aberrant) SAAs with an intrathoracic component. Mean SAA diameter was 3.1 cm (range, 1.6-6.0 cm). Mean patient age was 57 years (range, 24-80 years). Twenty-one percent (n = 4) of patients had a connective tissue disorder (two Loeys-Dietz, two Marfan). Thirty-six percent (n = 8) of SAAs were repaired by open techniques and 64% (n = 14) via a TEVAR-based approach. All TEVAR cases required proximal landing zone in the aortic arch (zone 0-2), and revascularization of at least one arch vessel was required in 83% (10/12) of patients. Concomitant repair of associated aortic pathology was performed in 50% (n = 10) of operations. Thirty-day/in-hospital rates of death, stroke, and permanent paraplegia/paraparesis were 5% (n = 1), 5% (n = 1), and 0%, respectively. Over mean (standard deviation) follow-up of 24 (21) months, 16% (n = 3) of patients required reintervention for subclavian artery bypass graft revision (n = 2) or type II endoleak (n = 1).ConclusionsThis is the largest single-institution series to date of TEVAR for SAA repair. Modern endovascular techniques expand SAA repair options with excellent results. The majority of SAAs and nearly all aberrant SAAs (Kommerell's diverticulum) can now be repaired using a TEVAR-based approach without the need for sternotomy or thoracotomy

The agroecology of malaria, maize, mosquitoes and dynamic landscape change in Ethiopia

PSAE Research Series No. 1

Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis

Introduction: Type 4 phosphodiesterases (PDE4) play an important role in immune cells through the hydrolysis of the second messenger, cAMP. Inhibition of PDE4 has previously been shown to suppress immune and inflammatory responses, demonstrating PDE4 to be a valid therapeutic target for immune-mediated pathologies. We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66102/1/j.1469-7793.2001.t01-1-00141.x.pd