Anti-DGKH monoclonal antibody, clone EML2133

On 5 September 1940, the German Society for Child Psychiatry and Therapeutic Education (DGKH) was founded. In order to secure sustainable impact, the young professional association aimed to: (1) Increase its scientific reputation through the organization of regular conventions and publications, (2) Attain continuity in its leadership (board) and membership growth, and (3) Establish itself in national socialistic politics and society for health care policy matters. Due to the unexpected death of the first chairman, Paul Schroder, only nine months after DGKH's foundation, these objectives were seriously put into question. The search for a new chairman led to a struggle for power and direction involving rival medical and non-medical associations as well as governmental institutions. Rather contrary to current knowledge, newly discovered documents indicate that the DGKH definitely acted out and initially influenced healthcare policy both before and directly after Schroeder's death. To interpret the complexity of the succession decision process - which led to the more radical Hans Heinze being chosen over Werner Villinger - this study employs a qualitative historical network analysis approach. For the broader interpretation of results within the national socialistic healthcare context we refer to Lutz Raphael's concept of radical order theory.

Background: DGKH is a replicated risk gene of bipolar disorder (BD). However, the pathophysiological role of the coded protein, diacylglycerol kinase eta, remains elusive. Methods: In this proof-of-concept study we isolated mRNA from peripheral blood and fibroblasts of heterozygote DGKH risk variants carriers (risk haplotype rs994856/rs9525580/rs9525584 GAT) with bipolar disorder and non-risk variant carriers with and without bipolar disorder. Gene expression of DGKH1, DGKH2, INPP5E, PI4K2B, PIK4CA, PLCG2, PRKCA, PRKCD, PRKCE and PRKCH was analysed by qRT PCR. Results: DGKH1 expression was increased in peripheral blood of risk variant carriers (p=0.027). In fibroblast cells, PRKCD expression was significantly increased in DGKH GAT carriers (p=0.037). Patients with a current depressive episode had lower PRKCD levels and lithium treatment was associated with increased PRKCA expression (p=0.005, and p=0.033). Limitations: No homozygote risk variant carriers and no healthy risk variant carriers were included due to their infrequency. Bipolar patients carrying the GAT haplotype were older with marginal significance, as age had also an influence on DGKH expression levels but not on PRKCD levels, replication with better age-matched samples and also bigger samples are needed. Conclusions: The results add evidence for the role of fibroblast cells and peripheral blood as useful tools in the functional characterisation of risk gene variants. Also a combination of genotyping and peripheral gene expression analysis could proof useful in the search of biomarkers for endophenotypes. Furthermore, we could confirm the role of the inositol-1,4,5-triphosphate second messenger pathway and protein kinase C in the pathogenesis of BD. (C) 2016 Elsevier B.V. All rights reserved.