A new type of metal recognition by human T cells: contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel

In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR-promiscuous VA22/VB17+ TCR is primarily harbored in its alpha chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR-associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1alpha, an N-nucleotide-encoded Tyr94 in CDR3alpha, and a conserved His81 in the HLA-DR beta chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR alpha chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3alpha-determined TCR amino acids. This new type of TCR-MHC linkage might explain the high frequency of Ni-reactive T cells in the human population.     

Die geschätzten Kosten von Neurodermitis bei Kindern

Using a sample of 204 children from Berlin who suffer from medium serious or serious atopic dermatitsl, the Berlin Centre for Public Health conducted a study about the costs of atopic dermatitis. The direct costs summed up to DM 5041 per year and child, only 15% of which was spent on doctors ‘appointments. Half of that went to non medical practitioners. Indirect costs per child and year amounted to another DM 3606 when gross wages were used to evaluate time consumption and DM 2669 when net wages were used. The parents had to cover more than 60% of the total costs.     

A comparison of patient questionnaires and composite indexes in routine care of rheumatoid arthritis patients

ObjectiveTo evaluate the agreement between the Routine Assessment of Patient Index Data 3 (RAPID-3) and a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI-5), as well as the Disease Activity Score including a 28 joint count (DAS28-ESR) and the Clinical Disease Activity Index (CDAI) in daily routine.MethodsOne hundred and twenty-eight rheumatoid arthritis (RA) out-patients completed the RADAI-5 and the RAPID-3. Simultaneously, the DAS28-ESR and the CDAI were applied. Cronbach's Alpha as a measure for reliability was calculated and factorial analysis was performed. For agreement analysis, Kendall's Tau was calculated.ResultsTime to score the questionnaires was 25 seconds. The median RADAI-5 was 2.8 (0–9.2), the median RAPID-3 3.3 (0–8.6), the median DAS28-ESR 2.95 (0.43–6.24), and the median CDAI 5.6 (0–37.5). Cronbach's Alpha for the RADAI-5 was 0.906 and 0.871 for the RAPID-3, however, only 0.165 for the DAS28-ESR and 0.210 for the CDAI, respectively. Factorial analysis revealed that both questionnaires and the DAS28-ESR, but not the CDAI, constitute mono-dimensional instruments. Tau for the agreement between the RADAI-5 and the RAPID-3 appeared to be 0.587 (p < 0.001), and to be 0.582 (p < 0.001) between the DAS28-ESR and the CDAI, while it was lower for the relationship between the questionnaires and the composite indexes.ConclusionReliability of the RAPID-3 and RADAI-5 was significantly higher than of the indexes. The questionnaires as well as the indexes proved to be in highly moderate agreement, while agreement between the questionnaires and the indexes appeared to be lower.     

Acquired von Willebrand syndrome after exchange of the HeartMate XVE to the HeartMate II ventricular assist device

Instead of pulsatile ventricular assist devices an increasing number of nonpulsatile ventricular assist devices are introduced to clinical practice. The different flow characteristics of this new technique lead to alteration in shear stress on blood components, which may affect the coagulation system. Repeated von Willebrand factor analyses were performed in a patient who first was implanted with a pulsatile ventricular assist device (Thoratec HeartMate XVE), which had to be replaced after 405 days with an axial flow device (HeartMate II). During support with the pulsatile ventricular assist device there was no sign of any coagulation disorder. However, on the axial flow device acquired von Willebrand syndrome Type 2 developed. Inhibition of platelet function was also observed, which may be in part due to the von Willebrand syndrome. The HeartMate II axial flow device may induce von Willebrand syndrome, which was not observed in HeartMate XVE pulsatile ventricular assist device. Patients put on continuous flow devices should be screened for acquired von Willebrand syndrome.     

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Psychotherapie Forum -     

Acute coronary syndrome associated with Churg-Strauss syndrome

A 41 -year old female patient was admitted with acute onset of dyspnea and chest pain. Previous history revealed asthma, chronic sinusitis and eosinophilic proctitis. Electrocardiogram showed anterior ST-segment elevations and inferior ST-segment depression. Immediate heart catheterization revealed a distally occluded left anterior descending coronary artery, the occlusion being reversible after nitroglycerine. Cardiac magnetic resonance imaging was consistent with perimyocarditis. Hypereosinophilia and IgE elevation were present and Churg-strauss syndrome was diagnosed.     

Plasmid-mediated quinolone resistance in isolates obtained in german intensive care units

Screening of 703 isolates of Enterobacteriaceae, obtained from 34 German intensive care units (ICUs), revealed qnr-positive, integron-containing isolates of Enterobacter sp. and Citrobacter freundii from four patients in 2 German ICUs. This is one of the first reports of qnr-positive strains obtained from patients in Europe.