Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis

The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits – multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) – in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Mass spectrometric characterization of high-valent metal-oxo, -peroxo and -peroxy intermediates of relevance in oxidation processes

The coupling of mass spectrometry with ionization techniques like electrospray ionization (ESI) or matrix-assisted matrix-assisted laser desorption-ionization (MALDI) offers many advantages over other well-established spectroscopic techniques employed for the investigation of intermediates or short-lived species in condensed-phase. In this review we describe some of the applications of mass spectrometry, in particular of ESI-MS to the detection and characterization of high-valent metal-oxo, -peroxo and -peroxy derivatives, crucial intermediates in the oxyfunctionalization of organic substrates. In addition, by utilizing gas-phase ion-molecule reactions and MS/MS experiments, information on the intrinsic reactivity of the short-lived intermediates may be obtained. The combined use of ESI-MS in association with other spectroscopic techniques and theoretical calculations is discussed as well. © 2006 Wiley Periodicals, Inc