Summary
A novel and recently launched food for special medical purposes was discussed by a multidisciplinary expert panel as an option for allergic patients. The newly developed lozenge contains the ...whey protein beta-lactoglobulin (BLG) as well as the micronutrients iron, zinc and vitamin A. BLG loaded with ligands (holo-BLG) is discussed as one factor of the allergy-protective farm effect in numerous scientific studies. Further studies reveal that holo-BLG shuttles its ligands specifically to immune cells, where it balances the specific nutrient demand and can thus lead to immune resilience. Based on the scientific background, the experts see a broad range of possible applications for holo-BLG in the form of a lozenge, for example in patients suffering from multiple allergies, with sensitisation to rare allergens (including occupational allergens), tree pollen-associated food allergies or in general difficult treatment situations (e.g. allergies to animal dander or refusal of allergen immunotherapy). The expert panel describes the holo-BLG lozenge as an innovative and additional option for allergic patients.
Sympathetic nervous system (SNS) activation mobilizes blood leukocytes. Under these circumstances, both epinephrine (EPI) and neuropeptide Y (NPY) are released. Therefore, we investigated a possible ...interaction between these transmitters during leukocyte mobilization, using intravenous catheterization of male adult Lewis rats. Intravenous application of NPY followed by EPI, dose-dependently facilitated, intensified and inhibited EPI-induced leukocytosis with subset-specificity for NK-cells, monocytes, and B-lymphocytes. Pharmacological assessment of NPY receptors involved revealed a Y-1R-mediated inhibition and a Y-5R-mediated facilitation. RT-PCR on peripheral blood mononuclear cells (PBMC) detected Y-1R mRNA only, suggesting direct Y-1R-mediated effects on leukocytes and indirect effects via the Y-5R. Thus, via a specific Y-1R/Y-5R interplay, NPY acts as a neuroimmune co-transmitter in vivo.
Unique functions of mammalian DNA- topoisomerases II alpha and - beta are suggested by their distinct cellular distribution and chromatin binding at mitosis. Here, we studied H69-VP cells that due to ...a homozygous mutation, express topoisomerase II alpha mostly outside the nucleus. In these cells topoisomerase II beta showed a normal nuclear localization. However, at mitosis it diffused away from the chromatin despite the nuclear lack of the alpha - isoform. 80% of these cells performed chromosome condensation and disjunction with the aid of cytosolic topoisomerase II alpha , which bound to the mitotic chromatin with low affinity. However, the genotype of these cells was highly polyploid indicating an increased rate of non- disjunction. In 20% of the mutant cells neither topoisomerase II isoform was bound to the mitotic chromatin, which appeared as an unstructured DNA spheroid unable to undergo disjunction and cytokinesis. Parental H69 cells expressing topoisomerase II alpha inside the nucleus exhibited high affinity binding of the enzyme to the mitotic chromatin. Their genotype was mostly diploid and stable. We conclude (i) that high affinity chromatin binding of topoisomerase II alpha is essential for chromosome condensation/disjunction and (ii) that topoisomerase II beta does not adopt these functions.
Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is ...unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing beta cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.
The fully automated generation of diagnostic codes requires a knowledge-based system which is capable of interpreting noun phrases. The sense content of the words must be analysed and represented for ...this purpose. The codes are then generated based on this representation.In comparison with other knowledge-based systems, a system of this kind places the emphasis on the data structures and not on the calculus; coding itself is a simple matter compared to the much more difficult task of incorporating the complex information contained in the words used in natural language in a systematic data model. Initial attempts were based on the assumption that each word was linked to one conceptual meaning, whereas such a naive viewpoint certainly no longer applies today. The notation of concepts and their relations is the task at hand.Existing notation methods include predicate logic, conceptual graphs (CGs) as proposed by J. F. Sowa 2, GRAIL as used by the GALEN Project 1 and methods developed as part of the WWW consortium, e.g. RDF's (Resource Description Frameworks). For the purpose of coding, we developed a notation system using "concept particles" back in 1989 3. In 1996, the resulting experience led us to represent "concept molecules" (CM), with which both complex data structures and multi-branched rules can be denoted in a simple manner 4. In this paper we shall explain the principles behind this notation and compare it with another modern concept representation system, conceptual graphs.
Unique functions of mammalian DNA-topoisomerases IIα and -β are suggested by their distinct cellular distribution and chromatin
binding at mitosis. Here, we studied H69-VP cells that, due to a ...homozygous mutation, express topoisomerase IIα mostly outside
the nucleus. In these cells topoisomerase IIβ showed a normal nuclear localization. However, at mitosis it diffused away from
the chromatin despite the nuclear lack of the α-isoform. 80% of these cells performed chromosome condensation and disjunction
with the aid of cytosolic topoisomerase IIα, which bound to the mitotic chromatin with low affinity. However, the genotype
of these cells was highly polyploid indicating an increased rate of non-disjunction. In 20% of the mutant cells neither topoisomerase
II isoform was bound to the mitotic chromatin, which appeared as an unstructured DNA spheroid unable to undergo disjunction
and cytokinesis. Parental H69 cells expressing topoisomerase IIα inside the nucleus exhibited high affinity binding of the
enzyme to the mitotic chromatin. Their genotype was mostly diploid and stable. We conclude (i) that high affinity chromatin
binding of topoisomerase IIα is essential for chromosome condensation/disjunction and (ii) that topoisomerase IIβ does not
adopt these functions.
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