No linkage or association of the IL-4Ralpha gene Q576R mutation with atopic asthma in Italian families.
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Biomedical subjects
Publications and source records attributed to G Zanoni.
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We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from Centre d'Etude du Polymorphisme Humain families. Affected sib pair multipoint linkage methods were used to perform the statistical analyses. We report suggestive linkage for asthma with markers on chromosome 12. The region of interest centers around marker D12S390 (maximum logarithm of odds [mlod] = 2.81; p = 0.003). These results provide additional support that asthma susceptibility factors are located on chromosome 12q.
Results from a medicinal chemistry approach aimed at replacing the quinoline ring system in the potent and selective human neurokinin-3 (hNK-3) receptor antagonists 1-4 of general formula I are discussed. The data give further insight upon the potential NK-3 pharmacophore. In particular, it is highlighted that both the benzene-condensed ring and the quinoline nitrogen are crucial determinants for optimal binding affinity to the hNK-3 receptor. Some novel compounds maintained part of the binding affinity to the receptor (5, 6, 10 and 13) and compound 5, featuring the naphthalene ring system, appears to be suitable for further modifications; it offers the option to introduce electron-withdrawing groups at position 2 and 4, conferring on the ring an overall electron-deficiency similar to that of the quinoline.
The involvement of immunological reactivity to ranitidine base (R-b) and ranitidine hydrochloride (R-HCl) in the development of occupationally related symptomatology was analyzed in 40 subjects employed in a pharmaceutical plant producing ranitidine and in 33 nonexposed controls, using a specific dose-response lymphocyte proliferative test (lymphocyte transformation test: LTT). Of the 40 workers, 11 (28%) gave positive reactions to LTT: 3/11 to R-b, 4/11 to R-HCl, and 4/11 to both compounds. None of the controls gave positive reactions. Cutaneous, oculonasal, or respiratory work-related symptoms were cited by 23 of the 40 (58%) subjects; ten of these 23 subjects (43%) were LTT positive. One asymptomatic case was LTT positive. The present results indicate that specific immune reactivity to ranitidine, analyzed by LTT, is associated with the presence of occupational symptomatology; R-HCl and R-b seem to share some antigenic determinants, because of the partial cross-reactivity shown by the examined compounds. Nonimmunological, probably irritative, mechanisms are also present in some of the symptomatic subjects.
Three immunoenzymatic techniques for specific IgE detection (Pharmacia CAP System, Kallestad Allercoat System, Neo Abellò Hamlet-IgE) and the classical Phadebas RAST were compared using 34 sera from patients with a clinical diagnosis of allergic disease and 19 sera from healthy non-atopic controls. IgE antibodies to 9 aeroallergens and 6 food antigens were assessed and 399 tests were run with each method. All techniques showed a high specificity (92%-100%) and satisfactory efficiency (82%-98%), while the sensitivity for RAST, CAP, Allercoat and Hamlet was 89%, 91%, 83% and 53%, respectively, with the lowest values for food allergens. There was a good overall correlation of the four techniques, except when the Hamlet method was compared with the other methods for food-specific IgE detection (correlation coefficient < 0.3). These data indicate that CAP, Allercoat and RAST are satisfactory techniques for specific IgE determination, either for inhalants or for food allergens; CAP, however, offers the highest sensitivity without loss of specificity.
Serum antibodies to four common food antigens, three cows' milk proteins (casein, alpha-lactalbumin and beta-lactoglobulin) and ovalbumin, were investigated in 21 children with atopic dermatitis (aged 3 months to 3 years) and in 15 age-matched healthy controls. Specific IgE was measured by radioallergosorbent test; an ELISA was developed to detect specific IgG, IgG subclasses and IgA. Specific IgE was found in 76% of patients, while antigen-directed IgG and IgA were present both in patients and healthy controls; IgG to ovalbumin and IgA to alpha-lactalbumin were significantly higher in children with atopic dermatitis. The analysis of the IgG subclass distribution showed different patterns of response, IgG1 and IgG4 being higher in patients (even though statistically significant only for ovalbumin), and IgG2 and IgG3 being lower in this group. The presence of food-specific IgE in the majority of atopic children and the different specific IgG subclass patterns observed in patients and controls may reflect an alteration in the immune response to dietary proteins in atopic dermatitis.
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Smoke as a carrier of atmospheric pollution, is able to break the barrier between external and internal environment of a respiring creature. Primary pollutants arise from all processes of combustion able to affect ecosystems or biologic mechanisms. Among physiologic factors influencing susceptibility to airway disease are size of contact-area between respiratory tissue and airways. Some airway diseases are influenced by pollution. The atmospheric and industrial pollutants irritant to airways are inevitable whereas the habit of smoking is at the own responsibility of each individual. The withdrawal programs for smokers of the association of Swiss physicians (FMH) and the Swiss Office of public health are fully supported.
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In a clinical survey the respective effects have been compared of venesection and of hypervolemic hemodilution on hematocrit and pressure in the pulmonary circulation. Whereas after venesection the pressure in the pulmonary circulation and the hematocrit decrease slightly, infusion of 1000 ml Macrodex is followed by marked hemodilution and a distinct increase in pressure in the pulmonary circulation.
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