SummaryTo identify components of the defense response that limit growth of a biotrophic fungal pathogen, we isolated Arabidopsis mutants with enhanced disease susceptibility to Erysiphe orontii. Our initial characterization focused on three mutants, eds14, eds15, and eds16. None of these is considerably more susceptible to a virulent strain of the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm). All three mutants develop a hypersensitive response when in®ltrated with Psm expressing the avirulence gene avrRpt2, which activates resistance via the LZ-NBS/LRR resistance protein encoded by RPS2. The growth of Psm(avrRpt2), while somewhat greater in the mutants than in the wild type, is less than growth of the isogenic virulent strain. These results indicate that resistance mediated via LZ-NBS/LRR R genes is functional. Analysis of the growth of avirulent Peronospora parasitica strains showed that the resistance pathway utilized by TIR-NBS/LRR R genes is also operative in all three mutants. Surprisingly, only eds14 and eds16 were more susceptible to Erysiphe cichoracearum. Analysis of the expression pro®les of PR-1, BGL2, PR-5 and PDF1.2 in eds14, eds15, and eds16 revealed differences from the wild type for all the lines. In contrast, these mutants were not signi®cantly different from wild type in the deposition of callose at sites of E. orontii penetration. All three mutants have reduced levels of salicylic acid after infection. eds16 was mapped to the lower arm of chromosome I and found by complementation tests to be allelic to the salicylic acid-de®cient mutant sid2.

We developed a modified allele-specific PCR procedure for assaying single nucleotide polymorphisms (SNPs) and used the procedure (called SNAP for single-nucleotide amplified polymorphisms) to generate 62 Arabidopsis mapping markers. SNAP primers contain a single base pair mismatch within three nucleotides from the 3Ј end of one allele (the specific allele) and in addition have a 3Ј mismatch with the nonspecific allele. A computer program called SNAPER was used to facilitate the design of primers that generate at least a 1,000-fold difference in the quantity of the amplification products from the specific and nonspecific SNP alleles. Because SNAP markers can be readily assayed by electrophoresis on standard agarose gels and because a public database of over 25,000 SNPs is available between the Arabidopsis Columbia and Landsberg erecta ecotypes, the SNAP method greatly facilitates the map-based cloning of Arabidopsis genes defined by a mutant phenotype.

INTRODUCTIONSesame seed is an emerging food allergen in the U.S. pediatric population as it becomes more common in the American diet. A recent systematic review of seed allergies described a prevalence of < 1% for sesame allergy as defined by a positive food challenge.1 It has been reported that most patients have sesame allergy before the age of 2 and about 20% of children with clinical allergy eventually develop tolerance.2 Another study described 9 of 30 children (30%) developing tolerance at an average age of 2.8 years.3 Dalal et al. reported anaphylaxis as the presenting symptom in 30% of children with sesame allergy, all occurring in patients less than 1 year of age.4 This is of significant clinical concern in children who are too young to describe their symptoms.Clinical diagnostic tests such as food-specific IgE levels and skin prick test (SPT) results may aid in deciding who will tolerate a food challenge compared to those who are likely to react.5 Diagnostic decision points for food-specific IgE antibodies have been published for common food allergens such as egg, milk, peanut and fish.6 , 7 However, there is conflicting data regarding the diagnostic value of sesame-specific IgE and SPT and currently there are no established thresholds that predict clinical reactivity. Zavalkoff et al. were unable to establish a sesame-specific IgE threshold with a 95% positive predictive value.8 In a paper published by Maloney et al., a fitted predicted probability curve of clinical reactivity to sesame in relation to sesame-specific IgE did not show a 90% or 95% predicted probability of a reaction.9 Lastly, Ho et al. identified a sesame SPT wheal diameter ≥ 8 mm as being predictive of a positive food challenge with > 95% accuracy.10 Oral food challenge was used as the gold standard by which performance characteristics (sensitivity, specificity, positive and negative predictive values) of sesame-specific IgE measurements and SPT wheal size were calculated. Receiver operator characteristic curve (ROC) analysis was utilized to determine a threshold that would differentiate children with true sesame allergy from those who are tolerant. The relationship between sensitization status and outcome measure was analyzed using logistic regression. Fitted predicted probability curves were plotted using the results from logistic regression.Serum samples were analyzed for sesame-specific IgE using an ImmunoCAP fluorescence enzyme immunoassay (Phadia AB, Portage, MI). The detection limit of the assay was 0.35 kU/L. A positive ImmunoCAP test was defined as ≥ 0.35 kU/L.Skin prick tests were performed in a standard fashion using the Multi-Test II device from Alk-Abello (Round Rock, TX) and commercially prepared extract from Greer Laboratories (Lenoir, NC). Negative controls with saline and positive controls with histamine were performed concurrently. The mean of the longest diameter and orthogonal diameter were measured in millimeters at 15 minutes. A positive SPT was defined as a wheal diameter ≥ 3 mm larger than the negative control....

Sesame and coconut are emerging food allergens in the US. We sought to examine whether children allergic to peanuts and tree nuts are at increased risk of having an allergy to sesame or coconut. We performed a retrospective chart review of children who underwent skin prick testing (SPT) to sesame and coconut and identified 191 children who underwent SPT to sesame and 40 to coconut. Children with sensitization or allergy to peanuts or tree nuts were not more likely to be sensitized or allergic to coconut. In conclusion, children with peanut or tree nut sensitization were more likely to be sensitized to sesame but not coconut. Children with clinical histories of both peanut and tree nut allergy were more likely to be allergic to sesame. Keywords sesame; coconut; peanut; tree nut; skin prick test; food allergy Pediatric food allergy is increasing in prevalence, and peanuts and tree nuts are among the most common causes of severe allergic reactions (1-3). Children with peanut or tree nut allergies may be at higher risk of developing allergies to previously less well recognized foods such as sesame (4-6) and coconut (7). With the high prevalence of peanut and tree nut allergy in the US and concern for potential cross-reactivity with sesame, allergists suggest screening peanut and tree nut allergic children for sesame allergy (8). With the recent consideration of coconut as a tree nut in food labeling practice, some allergists are testing for coconut as well (9).Sesame is an emerging food allergen in the US and carries a significant risk of severe reactions including anaphylaxis. In a case series from Israel, 30% of patients with sesame allergy had anaphylaxis as their first presenting symptom, and all were less than one year of age (10). Of significant clinical concern is that sesame allergy can begin in children who are too young to describe their symptoms, and the risk of severe allergic reactions is high (10-12). The prevalence of sesame allergy varies geographically, with increased allergy in regions of

Buprenorphine (Subutex), a semi-synthetic opiate alkaloid derivative with partial μ-opioid receptor agonist and κ-opioid receptor antagonist activity, is used for treatment of opioid dependence or as a long-acting analgesic (1). It is available in several forms including sublingual tablets and has a mean plasma elimination half-life of 37 hours (2). Like other opioids, it can cause hypersensitivity reactions by directly activating mast cells or basophils in an IgE-independent manner (3). Reactions to buprenorphine have been reported in clinical trials and post-marketing experience: the most common reactions include rashes, hives, and pruritus. Less common reactions include bronchospasm, angioedema, and anaphylactic shock (2). Such systemic reactions to buprenorphine, however, are rare (4,5). We now report on a 21-year-old woman with a six-year history of opioid dependence, who had hypersensitivity reactions to many opioid medications, including buprenorphine, heroin, oxycodone, hydrocodone, and methadone, and who was successfully desensitized to buprenorphine.In our patient, heroin caused severe hives, vomiting, coughing, and sensation of throat closing; oxycodone resulted in hives and vomiting; hydrocodone and methadone resulted in severe nausea and vomiting. After multiple unsuccessful attempts to quit using drugs on her own, she entered a substance abuse treatment program and achieved remission for eight months, treated with sublingual buprenorphine twice daily along with cetirizine daily to minimize adverse reactions. She initially tolerated buprenorphine with cetirizine without reactions, but six months into her treatment, after missing a dose of cetirizine, she developed hives, dizziness, and a sensation of throat closing. Although these symptoms improved with cetirizine, further buprenorphine doses were accompanied by skin tingling, flushing, hives, and sometimes also with facial edema, nausea, or respiratory symptoms (sensation of throat closing associated with coughing and difficulty breathing). Over the next two months, respiratory symptoms became more frequent and severe. Symptoms occurred several times per week, typically lasting 10 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript minutes, and improving with cetirizine. Because of these reactions, buprenorphine was discontinued and these symptoms abated. However, she then relapsed into heroin use, which caused severe reactions with hives, vomiting, diarrhea, and a sensation of throat closing, despite remaining on daily cetirizine. She was referred for further evaluation of buprenorphine allergy.Physical examination was notable for mild dermatographia. Laboratory evaluation was notable for baseline total tryptase that was initially mildly elevated at 18 ng/mL (reference range, 1-15 ng/mL); repeat 13 ng/mL. CBC showed 5% eosinophils, but was otherwise normal, as were LFTs and TSH. Because she required a minimum of several months of sublingual buprenorphine to treat her substance dependence, desensitization to buprenorphine was...