Penicilloyl peptides are recognized as T cell antigenic determinants in penicillin allergy

Although hapten immune responses have been intensively studied in the mouse, very little is known about hapten determinants involved in human allergic reactions. Penicillins, as chemically reactive compounds of low molecular weight, constitute typical examples of hapten allergens for humans. Penicillins become immunogenic only after covalent binding to carrier proteins and in this form frequently induced IgE-mediated allergic reactions in patients subjected to antibiotic treatment. However, our previous data strongly indicated that penicillins also form part of the epitopes contacting the antigen receptors of beta lactam-specific T cells in allergic individuals. We have therefore investigated the molecular constraints involved in the T cell immune response to penicillin G (Pen G). Designer peptides containing a DRB1*0401-binding motif and covalently modified with Pen G via a lysine epsilon-amino group were found to induce proliferation of Pen G-specific T cell clones. A precise positioning of the hapten molecule on the peptide backbone was required for optimal T cell recognition. Furthermore, we extended these observations from our designer peptides to show that a peptide sequence derived from a natural DRB1*1101-binding peptide modified in vitro with Pen G, also acquired antigenic properties. Our data for the first time provide insight into the manner in which allergenic haptens are recognized by human T cells involved in allergic reactions to drugs and suggest possible mechanisms leading to the onset of these adverse immune responses.     

Lipasekatalysierte Triglyceridumesterung in einem lösungsmittelfreien Prozeß I: Analytik und Umesterungskinetik

Lipase-Catalyzed Interesterification of Triglycerides in a Solvent-Free Process I: Analytics and Kinetics of the Interesterification The interesterification of lipids catalyzed by immobilized lipases is an interesting substitute to the chemical interesterification. Studies using an industrial manufactured biocatalyst in a solvent-free process were performed. The kinetics of the interesterification were examined as a function of temperature and water content of the reaction system. The reaction rate of the interesterification can be described with reversible first order reaction kinetics. A part of the triglycerides of the substrate is hydrolyzed by a lipasecatalyzed lipolysis. Hydrolysis products are 1,2(2,3) and 1,3-diglycerides. This shows that an unspecific interesterification is catalyzed if the residence time is extended.     

Design aspects of MOS-controlled thyristor elements: technology,simulation, and experimental results

2.5-kV thyristor devices have been fabricated with integrated MOS controlled n⁺-emitter shorts and a bipolar turn-on gate using a p-channel DMOS technology. Square-cell geometries with pitch variations ranging from 15 to 30 μm were implemented in one- and two-dimensional arrays with up to 20000 units. The impact of the cell pitch on the turn-off performance and the on-state voltage was studied for arrays with constant cathode area as well as for single-cell structures. By realizing MOS components with submicrometer channel lengths, scaled single cells are shown to turn off with current densities of several kiloamperes per square centimeter at a gate bias of 5 V. In the case of multi-cell ensembles, turn-off performance is limited due to inhomogeneous current distribution. Critical process parameters as well as the device behavior were optimized through multidimensional numerical simulation     

Structure of metal site in Cd-substituted His117Gly mutant of azurin with and without addition of imidazole derivatives

The present work uses 111mCd-perturbed angular correlations of gamma-rays (PAC) to investigate the structure of the metal site of the His117Gly mutant of Pseudomonas aeruginosa azurin in aqueous solution and the effect on the structure upon addition of the following exogenous ligands: imidazole, 4-methyl imidazole, 1-methyl imidazole, 2-methyl imidazole and histidine. The nuclear quadrupole interaction of cadmium bound to the mutant without addition of exogenous ligands shows a strong pH dependence with three different nuclear quadrupole interactions consistent with two pKa values at about 7.2 and 8.6 at 2 degrees C. Addition of the imidazole derivatives resulted in a significant change in the PAC spectrum showing that they coordinate. This is in accordance with observations by EPR for the same mutant with copper at the metal site [den Blaauwen, T. & Canters, G. W. (1993) J. Am. Chem. Soc. 115, 1121-1129]. However, whereas EPR and ultraviolet/visual absorption show that the characteristics of the wild-type copper protein are regained by addition of the imidazole derivatives with the exception of the possible bidentates (histidine and histamine), the comparison of the PAC results to model calculations shows that the cadmium ion must be fourfold coordinated in most cases, probably binding an additional water or hydroxide ligand. A fourfold coordination is in contrast to cadmium-substituted wild-type azurin where PAC data inferred a threefold coordination by a Cys and two His residues [Danielsen, E. Bauer, R., Hemmingsen, L., Andersen. M., Bjerrum, M. J., Butz, T., Tr?ger, W., Canters, G. W., Hoitink, C. W. G., Karlsson, G., Hansson, O. & Messerschmidt, A. (1995) J. Biol. Chem. 270, 573-580]     

Faculty and Student Attitudes Toward Community Service: A Comparative Analysis

The Humanitarian Engineering initiative, sponsored by the William and Flora Hewlett Foundation, at the Colorado School of Mines, is creating a program that will support engineering students in understanding their responsibility for solving community development problems that exist throughout the world. As part of this effort, data has been collected on faculty and student attitudes using the ‘Community Service Attitudes Scale,” developed and validated by Shiarella, McCarthy, and Tucker. During the fall 2004, 78 students and 34 faculty members responded to this instrument. Statistically significant differences were found between the attitudes of students and faculty, males and females, and among different age groupings with respect to service activities. A general finding was that faculty displayed better attitudes toward community service than the students.     

Evaluation of a dual-color flow cytometry immunophenotyping panel in a multicenter quality assurance program

A basic immunophenotyping panel that employed dual-color combinations of fluorescein isothiocyanate (FITC) and phycoerythrin (PE) conjugated monoclonal antibodies (mAb; FITC-CD45/PE-CD14, FITC-IgG1/PE-IgG2, FITC-CD3/PE-CD8, FITC-CD3/PE-CD4, FITC-CD3/PE-CD16 + PE-CD56, and PE-CD19) was utilized in a quality assurance program to determine whether the 4 laboratories participating in a multicenter AIDS study obtained similar lymphocyte subset percentage values for T cells, B cells, NK cells, and CD4+ and CD8+ T cells. Over a 1 1/2 year period, 78 shared peripheral blood specimens were prepared and analyzed in each laboratory. The CD45bright CD14- percentage for each specimen was used to correct that individual's lymphocyte subset values. Interlaboratory coefficients of variation (CV) for the human immunodeficiency virus type I (HIV) seronegative (n = 38) and HIV-seropositive (n = 40) specimens using this panel were < 3% for total T cells; < 5% for CD4+ T cells and CD8+ T cells; < or = 17% for B and NK cells; and < 8% for CD4T/CD8T ratios. The 6-tube basic immunophenotyping panel has several notable features: a) for clinical studies, it permits comprehensive evaluation of an individual's major lymphocyte subsets, i.e., T, B, NK, and CD4+ and CD8+ T cells; b) for interlaboratory proficiency testing programs, it allows the detection of differences among laboratories in measurements of several functionally distinct cell populations; and c) for within-sample quality assurance, it provides several quality control checks, including the lymphosum, i.e., the sum of an individual's corrected T+B+NK values, a sum that was generally 100 +/- 5% on the HIV-seronegative specimens analyzed in this study.