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Minor Determinants (minor + determinant)
Terms modified by Minor Determinants Selected AbstractsPPL and MDM skin test: New test kit is helpful in detecting immediate-type allergy to beta-lactamsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 4 2007Regina Treudler Summary Background: The diagnosis of PPL (major determinant) and MDM (minor determinant) sensitization as relevant allergens in beta-lactam allergy has been recently hampered by withdrawal from the market of formerly available test kits. We investigated a new PPL/MDM test kit in the work-up of beta-lactam allergy. Patients and Methods: 15 patients with history of beta-lactam allergy were investigated for specific IgE and received patch, skin prick (SPT) and intracutaneous tests (ICT; immediate and late readings) using the relevant beta-lactams. In addition the new test kit was used for parallel SPT and ICT. Results: 14 women and 1 man (16,73 years) with immediate (n = 7), delayed (n = 7) or unclear (n = 1) reactions to beta-lactams 8,300 months previously (penicillin G/V n = 3, aminopenicillins n = 7, cephalosporins n = 4, unknown n = 2) were tested. In patients with immediate type reactions, n = 2 had specific IgE, n = 4 reacted to the new test kit (n = 3 MDM, all of whom reacted exclusively to this test, n = 1 PPL). Two patients with non-immediate reactions reacted to other beta-lactams. Conclusions: Our data show that the new test kit may be helpful in detecting patients with immediate type allergy to beta-lactams. Without this test, in those three patients reacting exclusively to MDM, and oral provocation test would have been necessary to clarify their allergy. Data from larger groups of patients are needed to determine the sensitivity and specificity of this test kit. [source] Variation in synonymous codon use and DNA polymorphism within the Drosophila genomeJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2006N. BIERNE Abstract A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r2, 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called ,genetic draft' by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome. [source] Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin testJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2009H.-L. Qiao MD PhD Summary Background:, Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. Methods:, A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. Results:, The rate of positive reactions for the specific IgE antibodies was 59·40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39·10% (52) and 42·86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7·5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0·01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Conclusion:, Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increaes with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity. [source] Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillinALLERGY, Issue 5 2010M. J. Torres To cite this article: Torres MJ, Ariza A, Fernández J, Moreno E, Laguna JJ, Montańez MI, Ruiz-Sanchez AJ, Blanca M. Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin. Allergy 2010; 65: 590,596. Abstract Background:, Skin testing of subjects with immediate hypersensitivity to amoxicillin is performed using major and minor determinants of benzylpenicillin plus amoxicillin. However, sensitivity is not optimal, and other determinants need to be considered. We assessed the sensitivity of stable, well-characterized minor determinants of amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve skin test sensitivity. Methods:, Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by basophil activation test and RAST inhibition assay. Results:, Patients with immediate hypersensitivity to amoxicillin were selected: Group A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive to benzylpenicillin determinants; Group C (n = 10), skin test negative and amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and nine (50%) negative. In Group C, skin tests were negative. BAT was positive to amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine in four (7.8%). RAST inhibition studies showed > 50% inhibition in all sera, with the highest concentration of amoxicillin and amoxicilloic acid. Conclusions:, The combination of minor determinants of amoxicillin, amoxicilloic acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin alone. Further efforts are needed to find new structures to improve sensitivity in the diagnosis of immediate hypersensitivity to betalactams. [source] Skin testing for immediate hypersensitivity to betalactams: comparison between two commercial kitsALLERGY, Issue 8 2006J. L. Rodríguez-Bada Introduction:, Skin testing with major and minor determinants of benzylpenicillin is the recommended standard practice to evaluate subjects with immediate hypersensitivity to betalactams. The withdrawal of these products from the market has set us back to the early days, before the introduction of reagents for in vivo testing. Objectives:, To compare a recently released kit of benzylpenicillin conjugated to poly- l -lysine (PPL) and minor determinants mixture (MDM) with the previously existing kit in a positive control group of subjects sensitized to major and/or minor determinants of benzylpenicillin. Methods:, Skin tests with both kits were made in a group of positive subjects previously diagnosed with immediate hypersensitivity to penicillins and with positive results to PPL and/or MDM and in a negative control group. Radioallergosorbent test (RAST) inhibition assays with a pool of sera and individual samples were carried out to compare the inhibition capacity of PPL and MDM of both kits. Results:, Of 22 cases selected from our historical group, 14 were positive: eight to PPL, three to MDM and three to both. These results were equivalent for both kits. RAST inhibition studies showed similar potencies in the inhibition of PPL and MDM. Conclusions:, Both tests show similar results in terms of RAST inhibition assays and skin tests sensitivity and specificity in the groups selected. The new assay can be used for the same purpose and indications as the previous test. [source] Minimal effect of ketoconazole on cyclosporine (SangCyATM) oral absorption and first-pass metabolism in rats: evidence of a significant vehicle effect on SangCyA absorptionBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2002Susan Wong Abstract The current work evaluated the effect of the CYP3A inhibitor ketoconazole on the oral absorption and first-pass metabolism of cyclosporine administered as the SangCyA formulation. Groups of 6 male Sprague,Dawley rats were administered SangCyA (5 and 15 mg/kg) by oral gavage alone and with ketoconazole (30 mg/kg). Blood cyclosporine levels were measured over 6 h, encompassing the cyclosporine absorption window. A significant vehicle effect on SangCyA absorption was observed. Comparing a 15 mg/kg dose, cyclosporine Cmax (mean±SD 1.12±0.16 µg/ml) and AUC0,6 (5.34±0.71 µg h/ml) were 50% lower when propylene glycol was used as gavage vehicle instead of saline (2.19±0.94 µg/ml and 9.52±2.52 µg h/ml, respectively). Coefficients-of-variation for these parameters were halved in the propylene glycol vehicle however Tmax was unaffected. Ketoconazole increased cyclosporine Cmax and AUC0,6 by 50,60%, regardless of the vehicle or the cyclosporine dose, without altering Tmax (2,3 h). The small effect of ketoconazole suggests that CYP3A-mediated intestinal and first-pass hepatic metabolism are minor determinants of cyclosporine oral bioavailability in rats. Copyright © 2002 John Wiley & Sons, Ltd. [source] |