Sulfites

Key Concepts Sulfites are frequently used food and drug additives. Ingestion of sulfite residues has been documented to trigger asthmatic reactions in sensitive individuals. Sulfite-induced asthma occurs in less than 5% of asthmatic individuals, and those with severe, persistent asthma are at greatest risk. The diagnosis of sulfite-induced asthma is best made by blinded oral challenge with assessment of lung function. Labeling regulations in the United States alert sulfite-sensitive individuals to the presence of sulfites in foods, which must then be avoided

Soybean Oil Is Not Allergenic to Soybean-Sensitive Individuals

We have previously demonstrated that peanut oil is not allergenic to peanut-sensitive individuals. Seven soybean-sensitive patients were enrolled in a double-blind crossover study to determine whether ingestion of soybean oil can induce adverse reactions in such patients. All subjects had histories of systemic allergic reactions (urticaria, angioedema, wheezing, dyspnea, and/or vomiting) after soybean ingestion and had positive puncture skin tests with a 1:20 w/v glycerinated-saline whole soybean extract. Sera from six of the seven subjects were tested by RAST assay for the presence of specific IgE antibodies to soybean allergens. All patients had elevated levels of serum IgE antibodies to the crude soybean extract; binding values ranged from 2.3 to 28.1 times that of a negative control serum. Before the oral challenges, all patients demonstrated negative puncture skin tests to three commercially available soybean oils and to olive oil (control). On four separate days, patients were challenged with the individual soybean oils and to olive oil in random sequence. At 30-minute intervals, under constant observation, patients ingested 2, 5, and 8 ml of one of the soybean oils or olive oil contained in 1 ml capsules. No untoward reactions were observed with either the commercially available soybean oils or olive oil. Soybean oil ingestion does not appear to pose a risk to soybean-sensitive individuals

Prevalence of Sensitivity to Sulfiting Agents in Asthmatic Patients

Ingestion of sulfiting agents can induce wheezing in some asthmatic patients. However, neither the prevalence of sulfite sensitivity nor the clinical characteristics of the affected asthmatic population are known. In a prospective single-blind screening study, 120 non-steroid-dependent and 83 steroid-dependent asthmatic patients underwent challenge with oral capsules of potassium metabisulfite. Five non-steroid-dependent and 16 steroid-dependent asthmatic patients experienced a greater than 20 percent reduction in their one-second forced expiratory volume within 30 minutes following the oral challenge. Twelve of these sulfite reactors were rechallenged with metabisulfite capsules in a double-blind protocol. Under these conditions, only three of seven steroid-dependent patients had a positive response. Moreover, only one of five non-steroid-dependent patients had a response to double-blind challenge. On the basis of this challenge study, the best estimate of the prevalence of sulfite sensitivity in the asthmatic patients studied is 3.9 percent. This population, however, contained a larger number of steroid-dependent asthmatic patients than would be found in the general asthmatic population. It is concluded, therefore, that the prevalence of sulfite sensitivity in the asthmatic population as a whole would be less than 3.9 percent and that steroid-dependent asthmatic patients are most at risk

Identification of a Brazil-Nut Allergen in Transgenic Soybeans

Background: The nutritional quality of soybeans (Glycine max) is compromised by a relative deficiency of methionine in the protein fraction of the seeds. To improve the nutritional quality, methionine-rich 2S albumin from the Brazil nut (Bertholletia excelsa) has been introduced into transgenic soybeans. Since the Brazil nut is a known allergenic food, we assessed the allergenicity of the 2S albumin. Methods: The ability of proteins in transgenic and nontransgenic soybeans, Brazil nuts, and purified 2S albumin to bind to IgE in serum from subjects allergic to Brazil nuts was determined by radioallergosorbent tests (four subjects) and sodium dodecyl sulfate–polyacrylamidegel electrophoresis (nine subjects) with immunoblotting and autoradiography. Three subjects also underwent skin-prick testing with extracts of soybean, transgenic soybean, and Brazil nut. Results: On radioallergosorbent testing of pooled serum from four subjects allergic to Brazil nuts, protein extracts of transgenic soybean inhibited binding of IgE to Brazil-nut proteins. On immunoblotting, serum IgE from eight of nine subjects bound to purified 2S albumin from the Brazil nut and to proteins of similar molecular weight in the Brazil nut and the transgenic soybean. On skin-prick testing, three subjects had positive reactions to extracts of Brazil nut and transgenic soybean and negative reactions to soybean extract. Conclusions: The 2S albumin is probably a major Brazil-nut allergen, and the transgenic soybeans analyzed in this study contain this protein. Our study shows that an allergen from a food known to be allergenic can be transferred into another food by genetic engineering

Research in Mathematics Educational Technology: Current Trends and Future Demands

This systematic review of mathematics educational technology literature identified 1356 manuscripts addressing the integration of educational technology into mathematics instruction. The manuscripts were analyzed using three frameworks (Research Design, Teacher Knowledge, and TPACK) and three supplementary lenses (Data Sources, Outcomes, and NCTM Principles) to produce a database to support future research syntheses and meta-analyses. Preliminary analyses of student and teacher outcomes (e.g., knowledge, cognition, affect, and performance) suggest that the effects of incorporating graphing calculator and dynamic geometry technologies have been abundantly studied; however, the usefulness of the results was often limited by missing information regarding measures of validity, reliability, and/or trustworthiness

Sensitivity to Sulfited Foods among Sulfite-Sensitive Subjects with Asthma

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction

Involvement of Laminin Binding Integrins and Laminin-5 in Branching Morphogenesis of the Ureteric Bud during Kidney Development

AbstractBranching morphogenesis of the ureteric bud (UB) [induced by the metanephric mesenchyme (MM)] is necessary for normal kidney development. The role of integrins in this complex developmental process is not well understood. However, the recent advent of in vitro model systems to study branching of UB cells and isolated UB tissue makes possible a more detailed analysis of the integrins involved. We detected integrin subunits α3, α6, β1, and β4 in both the UB and cells derived from the early UB. Blocking the function of each of these integrin subunits individually markedly inhibited branching morphogenesis in cell culture models. However, inhibiting individual integrin function with blocking antibodies in whole kidney and isolated UB culture only partially inhibited UB branching morphogenesis, suggesting that, in these more complex in vitro systems, multiple integrins are involved in the branching program. In whole organ and isolated bud culture, marked retardation of UB branching was observed only when both α3 and α6 integrin subunits were inhibited. The α6 integrin subunit can be expressed as both α6β1 and α6β4, and both of these β subunits are important for UB branching morphogenesis in both cell and organ culture. Furthermore, laminin-5, a common ligand for integrins α3β1 and α6β4, was detected in the developing UB and shown to be required for normal UB branching morphogenesis in whole embryonic kidney organ culture as well as isolated UB culture. Together, these data from UB cell culture, organ culture, and isolated UB culture models indicate that both integrin α3 and α6 subunits play a direct role in UB branching morphogenesis, as opposed to being modulators of the inductive effects of mesenchyme on UB development. Furthermore the data are consistent with a role for laminin-5, acting through its α3β1 and/or α6β4 integrin receptors, in UB branching during nephrogenesis. These data may help to partially explain the renal phenotype seen in integrin α3 and α3/α6 subunit-deficient animals

Primary ciliary dyskinesia with normal ultrastructure:three-dimensional tomography detects absence of DNAH11

In primary ciliary dyskinesia (PCD), motile ciliary dysfunction arises from ciliary defects usually confirmed by transmission electron microscopy (TEM). In 30% of patients, such as those with DNAH11 mutations, apparently normal ultrastructure makes diagnosis difficult. Genetic analysis supports diagnosis, but may not identify definitive causal variants. Electron tomography, an extension of TEM, produces three-dimensional ultrastructural ciliary models with superior resolution to TEM. Our hypothesis is that tomography using existing patient samples will enable visualisation of DNAH11-associated ultrastructural defects. Dual axis tomograms from araldite-embedded nasal cilia were collected in 13 PCD patients with normal ultrastructure (DNAH11 n=7, HYDIN n=2, CCDC65 n=3 and DRC1 n=1) and six healthy controls, then analysed using IMOD and Chimera software. DNAH11 protein is localised to the proximal ciliary region. Within this region, electron tomography indicated a deficiency of >25% of proximal outer dynein arm volume in all patients with DNAH11 mutations (n=7) compared to other patients with PCD and normal ultrastructure (n=6) and healthy controls (n=6). DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously undetectable by TEM. Advantageously, electron tomography can be used on existing diagnostic samples and establishes a structural abnormality where ultrastructural studies were previously normal

CXC chemokines exhibit bactericidal activity against multidrug-resistant gram-negative pathogens

The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing 4-amino-4-deoxy-l-arabinose-modified lipid A were also found to be susceptible to chemokine-mediated antimicrobial activity. However, loss of PhoP/PhoQ autoregulatory control, caused by disruption of the gene encoding the negative regulator MgrB, limited the bactericidal effects of CXCL9 and CXCL10 in a variable, strain-specific manner. Cumulatively, these findings provide mechanistic insight into chemokine-mediated antimicrobial activity, highlight disparities amongst determinants of colistin resistance, and suggest that chemokine-mediated bactericidal effects merit additional investigation as a therapeutic avenue for treating infections caused by multidrug-resistant pathogens