Autoinflammatory Disease Reloaded: A Clinical Perspective

Our understanding of the etiology of autoinflammatory disease is growing rapidly. Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed

Effective Sample Size: Quick Estimation of the Effect of Related Samples in Genetic Case-Control Association Analyses

Correlated samples have been frequently avoided in case-control
genetic association
 studies in part because the methods for handling them are either not
easily implemented or not widely known. We
advocate one method for case-control association analysis of correlated
samples -- the effective sample size method -- as a simple and
accessible approach that does not require specialized computer programs.
The effective sample size method captures the variance inflation
of allele frequency estimation exactly, and can be used to modify the
chi-square test statistic, p-value, and 95% confidence interval of
odds-ratio simply by replacing the apparent number of allele counts with the
effective ones. For genotype frequency estimation, although a single
effective sample size is unable to completely characterize the variance inflation,
an averaged one can satisfactorily approximate the simulated result.
The effective sample size method is applied to the rheumatoid arthritis
siblings data collected from the North American Rheumatoid Arthritis Consortium (NARAC)
to establish a significant association with the interferon-induced
helicasel gene (IFIH1) previously being identified as a type 1 diabetes
susceptibility locus. Connections between the effective sample size
method and other methods, such as generalized estimation equation,
variance of eigenvalues for correlation matrices, and genomic controls,
are also discussed.
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Use of Oxyrase® enzyme to enhance recovery of Escherichia coli O157:H7 from culture media and ground beef

Escherichia coli O157:H7 is a bacterium that has caused great concern in the meat and food industry during the last few years because of several, well-publicized, disease outbreaks, including the incident at the Jackin- the-Box fast food chain in Seattle, Washington. The organism can cause severe sickness and even death in certain population groups. To better assure meat safety, federal meat inspection is focusing on developing rapid methods to detect this disease agent and others. Oxyrase is a commercially available enzyme that can accelerate the growth of some bacteria. Current techniques for isolation and culturing of E. coli O157:H7 from foods require an enrichment period of 18 to 24 hours, thus limiting their usefulness for perishable foods that are marketed quickly. Our investigation found that Oxyrase shortened required enrichment periods in broth culture only. The enzyme was less effective in sterilized ground beef

Microbial flora of commercially produced vacuum packaged, cooked beef roast

Commercially produced vacuum packaged, fully cooked, microwaveable beef roasts from four producers were purchased from local retail markets. Salt concentration, pH, water activity (aw), and percent moisture, fat and protein were determined. Samples of both package juice and homogenized beef plus juice were analyzed for the presence of aerobic, anaerobic and lactic acid bacteria and clostridia-type organisms. The cooked beef products had pH values from 5.82 to 6.19, water activity of 0.992 to 0.997, and contained 0.34 to 1.07% salt, 61.89 to 72.39% moisture, 4.29 to 18.21% fat and 15.92 to 20.62% protein. No growth was detected in juice for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Combined beef and juice had less than 2 CFU/g for aerobic, anaerobic or lactic acid bacteria or clostridia-type organisms. Cooking and chilling schedules used in the manufacture of the four products we evaluated in this study limited survival and outgrowth of microorganisms

MF2293

Fadi Aramouni et al, Food safety, Kansas State University, October 1997

Pyrin Modulates the Intracellular Distribution of PSTPIP1

PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1 cause PAPA syndrome (Pyogenic sterile Arthritis, Pyoderma gangrenosum, and Acne), an autoinflammatory disease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder. Since disease-associated mutations in PSTPIP1 enhance pyrin binding, PAPA syndrome and FMF are thought to share a common pathoetiology. The studies outlined here describe several new aspects of PSTPIP1 and pyrin biology. We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associated filaments in native and transfected cells. An extended FCH (Fes-Cip4 homology) domain in PSTPIP1 is necessary and sufficient for its self-aggregation. We further show that the PSTPIP1 filament network is dependent upon an intact tubulin cytoskeleton and that the distribution of this network can be modulated by pyrin, indicating that this is a dynamic structure. Finally, we demonstrate that pyrin can recruit PSTPIP1 into aggregations (specks) of ASC, another pyrin binding protein. ASC specks are associated with inflammasome activity. PSTPIP1 molecules with PAPA-associated mutations are recruited by pyrin to ASC specks with particularly high efficiency, suggesting a unique mechanism underlying the robust inflammatory phenotype of PAPA syndrome

From second to first order transitions in a disordered quantum magnet

We study the spin-glass transition in a disordered quantum model. There is a region in the phase diagram where quantum effects are small and the phase transition is second order, as in the classical case. In another region, quantum fluctuations drive the transition first order. Across the first order line the susceptibility is discontinuous and shows hysteresis. Our findings reproduce qualitatively observations on LiHo$_x$Y$_{1-x}$F$_4$. We also discuss a marginally stable spin-glass state and derive some results previously obtained from the real-time dynamics of the model coupled to a bath.Comment: 4 pages, 3 figures, RevTe

Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review

PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the “inflammasome” involved in interleukin-1 (IL-1β) production. Overproduction of IL-1β is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical pathways that may be relevant to the distinct pyogenic inflammation of the skin and joints characteristic of this disease. This review summarizes the recent and rapidly accumulating knowledge on these molecular aspects of PAPA syndrome and related disorders

Data for Genetic Analysis Workshop 16 Problem 1, Association Analysis of Rheumatoid Arthritis Data

For Genetic Analysis Workshop 16 Problem 1, we provided data for genome-wide association analysis of rheumatoid arthritis. Single-nucleotide polymorphism (SNP) genotype data were provided for 868 cases and 1194 controls that had been assayed using an Illumina 550 k platform. In addition, phenotypic data were provided from genotyping DRB1 alleles, which were classified according to the rheumatoid arthritis shared epitope, levels of anti-cyclic citrullinated peptide, and levels of rheumatoid factor IgM. Several questions could be addressed using the data, including analysis of genetic associations using single SNPs or haplotypes, as well as gene-gene and genetic analysis of SNPs for qualitative and quantitative factors