Therapeutics in food allergy: the current state of the art.

Food allergy is an increasing public health dilemma in Westernized countries, yet no viable treatments are currently available for those who are afflicted. The only options available for patients with food allergies are prevention of reactions by strict avoidance of the offending food(s) and symptomatic treatment of any adverse effects from accidental exposures. Approaches are being pursued to develop treatments, and allergen-specific therapies such as oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy with different foods have shown promise. Other modalities are also being investigated, potentially leading to the discovery of novel therapeutic options.

Peanut allergy: an evolving clinical challenge.

Peanut allergy is an IgE-mediated food allergy responsible for causing severe and occasionally fatal reactions in those sensitized to peanuts. The prevalence of peanut allergy appears to be on the rise worldwide, yet there are no therapeutics currently available that can alter the course of this condition. This article will review the epidemiology, pathogenesis, and clinical features of peanut allergy and discuss future possibilities in diagnostic and therapeutic modalities.

Mouse allergens in urban elementary schools and homes of children with asthma.

BACKGROUND: The association between allergens in schools and childhood asthma has not been well studied, particularly in the United States. OBJECTIVE: To investigate allergen exposure in schools compared with homes with a specific focus on children with asthma. METHODS: Dust samples were collected from 46 rooms in 4 urban elementary schools (northeastern United States) and from 38 student bedrooms. Samples were analyzed for cat (Fel d 1), dog (Can f 1), cockroach (Bla g 2), dust mites (Der f 1/Der p 1), and mouse urinary protein (MUP). Questionnaires identified students with physician-diagnosed asthma. RESULTS: Cat and dog allergens were detectable in most school samples (96% and 78%, respectively), but at low levels. Cockroach allergen was detectable in only 11% of school samples. Mouse allergen was detectable in 89% of school samples, with 68% having MUP levels greater than 0.5 microg/g. In contrast, MUP was detectable in only 26% of bedroom samples. Matched classroom and home samples from 23 asthmatic students showed higher geometric mean MUP levels in the classroom vs the home (6.45 microg/g vs 0.44 microg/g, P < .001). However, there were lower geometric mean dust mite (Der f 1) levels in the classroom vs the home (0.04 microg/g vs 0.66 microg/g, P < .001). CONCLUSIONS: There are significantly higher levels of MUP but lower levels of Der f 1 in schools vs homes. It is important to recognize that children with asthma may encounter varying levels of allergens in environments outside the home, such as schools.

The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.

Uracil phosphoribosyltransferase (UPRT) is a member of a large family of salvage and biosynthetic enzymes, the phosphoribosyltransferases, and catalyzes the transfer of ribose 5-phosphate from alpha-d-5-phosphoribosyl-1-pyrophosphate (PRPP) to the N1 nitrogen of uracil. The UPRT from the opportunistic pathogen Toxoplasma gondii represents a promising target for rational drug design, because it can create intracellular, lethal nucleotides from subversive substrates. However, the development of such compounds requires a detailed understanding of the catalytic mechanism. Toward this end we determined the crystal structure of the T. gondii UPRT bound to uracil and cPRPP, a nonhydrolyzable PRPP analogue, to 2.5-A resolution. The structure suggests that the catalytic mechanism is substrate-assisted, and a tetramer would be the more active oligomeric form of the enzyme. Subsequent biochemical studies revealed that GTP binding, which has been suggested to play a role in catalysis by other UPRTs, causes a 6-fold activation of the T. gondii enzyme and strikingly stabilizes the tetramer form. The basis for stabilization was revealed in the 2.45-A resolution structure of the UPRT-GTP complex, whereby residues from three subunits contributed to GTP binding. Thus, our studies reveal an allosteric mechanism involving nucleotide stabilization of a more active, higher order oligomer. Such regulation of UPRT could play a role in the balance of purine and pyrimidine nucleotide pools in the cell.