21 research outputs found
ANCA-associated vasculitis.
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients
Criminogenic Policy as a Crime of the Powerful: A Case Study on NAFTAâs Negotiation Process
From a distance and generalizable to up close and grounded: Reclaiming a place for qualitative methods in international business research
Strong Metal Ion Size Based Selectivity of the Highly Preorganized Ligand PDA (1,10-Phenanthroline-2,9-dicarboxylic Acid) with Trivalent Metal Ions. A Crystallographic, Fluorometric, and Thermodynamic Study
Copper-Catalyzed Oxidative Dehydrogenative Carboxylation of Unactivated Alkanes to Allylic Esters via Alkenes
We
report copper-catalyzed oxidative dehydrogenative carboxylÂation
(ODC) of unactivated alkanes with various substituted benzoic acids
to produce the corresponding allylic esters. Spectroscopic studies
(EPR, UVâvis) revealed that the resting state of the catalyst
is [(BPI)ÂCuÂ(O<sub>2</sub>CPh)] (<b>1-O</b><sub><b>2</b></sub><b>CPh</b>), formed from [(BPI)ÂCuÂ(PPh<sub>3</sub>)<sub>2</sub>], oxidant, and benzoic acid. Catalytic and stoichiometric
reactions of <b>1-O</b><sub><b>2</b></sub><b>CPh</b> with alkyl radicals and radical probes imply that CâH bond
cleavage occurs by a <i>tert</i>-butoxy radical. In addition,
the deuterium kinetic isotope effect from reactions of cycloÂhexane
and <i>d</i><sub>12</sub>-cycloÂhexane in separate
vessels showed that the turnover-limiting step for the ODC of cycloÂhexane
is CâH bond cleavage. To understand the origin of the difference
in products formed from copper-catalyzed amidÂation and copper-catalyzed
ODC, reactions of an alkyl radical with a series of copperâcarboxylate,
copperâamidate, and copperâimidate complexes were performed.
The results of competition experiments revealed that the relative
rate of reaction of alkyl radicals with the copper complexes follows
the trend CuÂ(II)âamidate > CuÂ(II)âimidate > CuÂ(II)âbenzoate.
Consistent with this trend, CuÂ(II)âamidates and CuÂ(II)âbenzoates
containing more electron-rich aryl groups on the benzamidate and benzoate
react faster with the alkyl radical than do those with more electron-poor
aryl groups on these ligands to produce the corresponding products.
These data on the ODC of cycloÂhexane led to preliminary investigÂation
of copper-catalyzed oxidative dehydrogenative aminÂation of cycloÂhexane
to generate a mixture of <i>N</i>-alkyl and <i>N</i>-allylic products