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Am 29. Juni 1967 starb der deutsche Neurologe und Psychiater Franz Kramer (*1878) im niederlandischen Bilthoven. In einem Nachruf wurdigte Hermann Stutte (1909–1982), erster deutscher Ordinarius fur Kinder- und Jugendpsychiatrie, Kramers Verdienste „um die Reform der Erziehungsfursorge, die heilpadagogische Behandlung geistig behinderter Kinder und eine psychologisch orientierte forensische Behandlung jugendlicher Rechtsbrecher in Deutschland. … Die europaische Kinderpsychiatrie hat allen Anlass, sich dieses Pioniers, dem durch die apokalyptischen Zeitumstande die Weiterfuhrung seiner wissenschaftlichen Arbeiten unterbunden wurde … in Verehrung und mit Dankbarkeit zu erinnern.“ Doch erst seit der Jahrtausendwende ruckt dieser fruhe kinderpsychiatrische Protagonist als Erstbeschreiber der als Kramer-Pollnow-Syndrom bezeichneten hyperkinetischen Erkrankung des Kindesalters wieder verstarkt in den Fokus der wissenschaftshistorischen Aufmerksamkeit.

The psychiatric patients killed under the disguise of euthanasia during World War II belong to the group of victims which are often forgotten in public remembrance. For German and Austrian psychiatry it is important to include them into the memory of the discipline as well as into European remembrance of the victims of Nazi annihilation policy. The patient files of the victims enable us to reconstruct the criterion of economic usefulness for deciding about life or death. But above all the files are the basis on which the suffering and the life histories of the patients can be told.

// Ellen Umlauf 1 , Eduard Rappold 1 , Bettina Schiller 1 , Petra Fuchs 2 , Michael Rainer 3 , Brigitte Wolf 4 and Maria Zellner 1 1 Medical University of Vienna, Center of Physiology and Pharmacology, Institute of Physiology, Vienna, Austria 2 SMZ Otto Wagner Spital, 3rd Department of Psychiatry, Vienna, Austria 3 SMZ Ost, Karl Landsteiner Institut fur Gedachtnis- und Alzheimerforschung, Vienna, Austria 4 Medical University of Vienna, Surgery Research Laboratory, Department of Surgery, Vienna, Austria Correspondence to: Maria Zellner, email: // Keywords : Alzheimer’s disease, MCI, CERAD-Plus, MMSE, well-defined control group, Gerotarget Received : November 19, 2015 Accepted : May 25, 2016 Published : June 01, 2016 Abstract Approximately 30 million people currently suffer from late-onset Alzheimer’s disease (LOAD) worldwide. Twin studies demonstrated that 60 to 80% of LOAD is genetically determined, 20% of which remaining unassigned. This case-control study included 118 cognitively healthy controls, 52 patients with mild cognitive impairment (MCI; the pre-stage of LOAD) and 71 LOAD patients. The participants were genotyped for the genetic LOAD marker apolipoprotein E4 ( APOE4 ) and the single-nucleotide polymorphism rs4925 in glutathione S-transferase omega-1 ( GSTO1 ). Additive logistic regression showed a novel, statistically significant association of the major allele GSTO1*C with MCI (OR1.9; p = 0.032). However, identification of significant SNP-disease relations required well-defined study groups. When classifying participants solely by the short Mini Mental State examination (MMSE), the associations of GSTO1*C and the reference marker APOE4 with MCI were cancelled. Moreover, even identifying only the control group by MMSE nullified a statistically significant association (OR1.8; p = 0.045) between GSTO1*C and LOAD. In contrast, these statistical relations were retained when the detailed Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-Plus) test battery was used. Hence, besides proposing rs4925 as a genetic marker for cognitive impairment, this work also emphasized the importance of carefully characterized controls in addition to well-diagnosed patients in case-control studies.

This article describes Nazi crimes against the mentally ill during World War II. The main focus is the T4 Action, the first extermination campaign in national socialist Germany, which is widely considered a precursor to the Holocaust. The first part of the paper presents historical facts regarding the T4 Action: its ideological background, its characteristic organization, and secret structures; the parallels between this inner war and the war that was being waged against other nations; the rigorous methodology-from the filling out of "special forms" (meldebogen) to death in the gas chamber at one of six extermination centers. The second part of the paper is based on our own research on the victims' medical files, now available in the Federal Archives of Germany. The history of how the current archival material was discovered is touched on briefly. The T4 selection criteria are analyzed. As an example, events at the Uchtspringe asylum are described in detail. We attempt to distinguish among potential motiv...

The first synthesis of [26,27-2H6]24-epi-cathasterone 8via (20S)-3β-acetoxy-6,6-(ethylenedioxy)-20-formyl-5α-pregnane 5 starting from stigmasterol is described. The aldehyde 5 was alkylated with lithium butyldimethyl-(E)-2,3-dimethyl[3,3,3,4,4,4-2H6]butenylaluminate 6 prepared from 3-[2H3]methyl[4,4,4-2H3]but-1-yne. The structure was determined using spectral data and X-ray crystallographic analysis.

The distribution of GA20 and GA20-13-O-glucoside was examined in mature caryopses of Hordeum vulgare L. cv. Himalaya. It was shown by GC-MS that GA20-13-O-glucoside is localized mainly in the embryo-containing part of the grain. In order to study the reconversion of GA20-13-O-glucoside during early germination, the glucoside pool of cv. Himalaya was [17-D2]-labelled by feeding [17-D2]GA20. The metabolites of [17-D2]GA20-13-O-glucoside were quantified by GC-MS during germination on the basis of doubly labelled standards. As soon as 6 h after incubation an increase of [17-D2]GA20 could be observed, followed by an increase of [17-D2]GA1 after 12 h, showing that the enzymes of the late GA metabolism are present before de novo biosynthesis started.

Gibberellin A 20 -13- O -glucoside (GA 20 -13- O -Glc) and GA 8 -2- O -Glc were identified by GC-MS as permethylated derivatives in mature grains of both barley varieties Hordeum vulgare L. cv. Himalaya and cv. Salome. Changes of the pool size of these GA conjugates together with those of the parent GA 20 and GA 8 were estimated during seed ripening by internal standard quantification. The pools of GA 20 and GA 8 were found to reach a maximum and then to decrease to small amounts at the stage of full ripeness. The amounts of GA 20 -13- O -Glc were higher at the beginning of ripeness and then declined until full ripeness but these changes were not as pronounced as for free GA 20 . Thus, in mature caryopses of both varieties cv. Himalaya and cv. Salome the content of GA 20 -13- O -Glc was three to four times higher than that of GA 20 . The pool of GA 8 -2- O -Glc increased dramatically during the final stages of ripening, in cv. Himalaya earlier than in cv. Salome, and reflected the intensive GA 20 metabolism during ripening. This is the first report on the simultaneous quantification of the pools of GA- O -glucosides and their parent GAs during seed development on the basis of a GC-MS/internal standard technique.

An efficient route for an alternative synthesis of gibberllin A1 from gibberellin A3 is described. Based on iodolactonisation the method provides access to gibberellin A1 labeled by deuterium with both high incorporation of the isotope and high stereoselectity at the positions 1β and 2α. The additional deuterium labeling at C-17 was introduced via the corresponding 16-norketone resulting in [1β,2α,17,17-D4] gibberellin A1.

The synthesis of GA34-β- d -glucopyranosyl ester and of GA 34 -2-O-β- d -glucopyranoside starting from GA34-16-norketone methyl ester are described. The structures of the synthesized compounds were confirmed by NMR and by electrospray ionization-mass spectrometry.

An efficient route for an alternative synthesis of gibberllin A1 from gibberellin A3 is described. Based on iodolactonisation the method provides access to gibberellin A1 labeled by deuterium with both high incorporation of the isotope and high stereoselectity at the positions 1β and 2α. The additional deuterium labeling at C-17 was introduced via the corresponding 16-norketone resulting in [1β,2α,17,17-D4] gibberellin A1.

Background: In the past, different research groups could show that treatment of immune cells with inhibitors of post-proline splitting dipeptidyl aminopeptidases leads to functional changes in the immune system consistent with immunosuppression. This is due to the inhibition of proliferation of lymphocytes and the production of inflammatory cytokines of the TH 1 , TH 2 , and TH 17 cells as well as the induction of immunosuppressive cytokines, such as transforming growth factor-β1 (TGF-β1) and interleukin (IL)-1RA. Until recently, most of the effects of these inhibitors on immune functions were attributed to the inhibition of dipeptidyl aminopeptidase IV (DPIV/CD26). With the identification of new peptidases of the DPIV family (DASH) with the same or similar substrate specificity [fibroblast activation protein (FAP), DP8/9], the question arose whether and to what extent the inhibition of intracellularly localized enzymes, DP8 and DP9, contribute to the observed immunosuppression. In addition, members of the aminopeptidase N (APN) family are also involved in the regulation of immune functions. Hence, the concept of a combined targeting of both families of peptidases for treatment of inflammatory diseases is a promising strategy. Results/Conclusions: Summarizing data obtained from the usage of different non-selective and selective inhibitors of DPIV, DP8/9, FAP, and DPII, this review provides evidence that in addition to DPIV, DP8/9 also regulate the immune response via modulation of cell cycle progression and cytokine production. The strongest and most consistent effects in vitro were, however, observed with non-selective inhibitors for the suppression of DNA synthesis and cytokine production. Similar effects were provoked by APN inhibitors, which were also found to suppress DNA synthesis and the production of inflammatory cytokines in vitro. However, different mechanisms and signaling pathways appear to mediate the cellular effects resulting from the inhibition of either APN or DPIV family members. In particular, members of the APN family uniquely influence the function of CD4 + CD25 + regulatory T-cells. Consequently, the concomitant inhibition of both APN and DPIV enzyme families by means of two separate inhibitors or by binary inhibitors with specificity for both enzyme families (PETIR™, peptidase targeted immunoregulation) synergistically affects immune cells on the level of cell cycle regulation, suppression of TH 1 , TH 2 , and TH 17 cytokines as well as the activation of regulatory T-cells. Besides leukocytes, dermal cells as sebocytes, keratinocytes, and fibroblasts are also targeted by these inhibitors. This strongly suggests a broad potential of the multiple anti-inflammatory effects of PETIR™ in treatment of chronic inflammatory diseases, such as autoimmune diseases, allergies, and transplant rejections, as well as of inflammatory skin diseases, such as acne, psoriasis, rosacea or atopic dermatitis. The first active dual inhibitor, IP10.C8, has been developed by IMTM for the treatment of inflammatory skin diseases and has just entered the first phase II study.

During World War II, psychiatric patients hospitalized in asylums in Eastern Prussia became victims of two separate killing programmes: first, by the SS-special command Lange, second by the centrally (in Berlin) organized "euthanasia"-"Aktion T4". By an analysis of the patient files of the victims, the present paper shows that the historical actors responsible for the killings were communicating with each other. It is now also possible to reconstruct the exact dynamic in time and space of the killings. A comparative analysis of the selection criteria within the total population of the asylums documents that in both programs, the responsible historical actors included physicians and provincial administrative personnel; it further shows that under the conditions of war, only patients who were able to contribute to the asylum work and economy, and were behaviourally adapted could survive.

The ectopeptidases Dipeptidylpeptidase IV and Alanyl-Aminopeptidase N, strongly expressed by both, activated and regulatory T cells were shown to co-operate in T cell regulation. Based on the findings that DPIV and APN inhibitors induce the TGF-beta1 and IL-10 production and a suppression of T helper cell proliferation in parallel, and that particularly APN inhibitors amplify the suppressing activity of regulatory T cells, both peptidases represent a promising target complex for treatment of diseases associated with an imbalanced T cell response, such as inflammatory bowel diseases (IBD). The aim of the present study was to analyze the therapeutic potential of DPIV and APN inhibitors in vivo in a mouse model of colitis. Balb/c mice received 3% (w/v) dextran sulphate sodium with the drinking water for 7 days. After onset of colitis symptoms, inhibitor treatment started at day 3. Disease activity index (DAI) was assessed daily, supplemented by histological and immunological analysis. While the DPIV inhibitor Lys-[Z(NO])(2)]-pyrrolidide or the APN-inhibitor Actinonin alone had marked but no significant therapeutic effects, the simultaneous administration of both inhibitors reduced colitis activity in comparison to placebo treated mice, significantly (DAI 4.8 vs. 7.7, p

The question addressed in the present study is whether children and adults are able to combine and decompose separate kinematic (visual-feedback-shift) and dynamic (velocity-dependent force) transformations in goal-directed arm movements. A total of 64 participants (32 adults and 32 children) performed horizontal forearm movements using a single-joint arm manipulandum. When participants first learned kinematic and dynamic transformations separately, target error decreased in a subsequent combined transformation task. This effect was based on previous learning of the kinematic transformation. When they first learned the combined transformation, target error was smaller in the following kinematic—but not in the dynamic—transformation. No difference was found in adaptation performance between children and adults. The results suggest that there are two separate models for the kinematic and dynamic transformation and that a possible differentiation of kinematic and dynamic features of the motor task might already be present at age 11.

Die Therapie des Facio-Oralen Trakts nach Coombes ist wissenschaftlich nicht bewiesen — und doch findet sie zunehmend Verbreitung. Damit befindet sie sich in guter Gesellschaft mit anderen bewahrten und weit verbreiteten Therapiekonzepten wie z. B. dem Bobath-Konzept oder der Re-flexlokomotion nach Vojta. In den letzten Jahren, u. a. als Folge des Drucks Kosten im Gesundheitswesen zu reduzieren, wird der Ruf nach evidence-based medicine, einer auf wissenschaftlichen Beweisen basierenden Medizin laut. De facto gibt es aber kaum Studien uber physio- und ergo-therapeutische oder logopadische Behandlungsansatze, die wissenschaftlichen Kriterien standhalten. Diese Therapieansatze waren zum einen bisher kaum Thema wissenschaftlichen Interesses, zum anderen stellen sich in der vergleichsweisejungen Disziplin Neurorehabilitation-z. B.im Vergleich zu einer Medikamentenwirksamkeitsprufung eine Vielzahl ethischer und methodischer Fragen.

[17- 2 H 2 ]GA 20 -13-O-[6'- 2 H 2 ]glucoside was synthesized and applied to seedlings of Phaseolus coccineus L. After incubation for 72 h the conjugate metabolites were purified and shown by LC-ESI-tandem-MS and GC-MS to be [17- 2 H 2 ]GA 1 -13-O-[6'- 2 H 2 ]glucoside and [17- 2 H 2 ]GA 29 -13-O-[6'- 2 H 2 ]glucoside. This is the first evidence for the conversion of intact GA-O-glucosides, and represents an additional metabolic pathway of the gibberellin metabolism in P. coccineus L. The results indicate that intact GA-O-glucosides are accepted by 2- and 3-oxidases in the plant.

The relative DNA levels of different developmental stages of Babesia bigemina and B. canis were measured by cytophotometry using the fluorochrome Hoechst 33258 as a staining dye. The DNA measurements provided direct proof of sexual reproduction, i.e., fusion of gametes resulting in the formation of zygotes followed by a meiotic division. Both Babesia species are considered to be typical members of the genus Babesia; however, the DNA measurements revealed important differences in the life cycle of these parasites, indicating that Babesia species are not characterized by a life cycle, which is specific for this genus.