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Prusa A.-R.,Intensive Care and Neuropaediatry | Wiedermann U.,Center for Pathophysiology | Kasper D.C.,Medical University of Vienna | Hayde M.,Intensive Care and Neuropaediatry | And 3 more authors.
Neonatology | Year: 2011

Objective: In consideration of comprehensive and well-established vaccination programmes in industrialized countries, it is expected that immunity against tetanus among expectant mothers and their offspring is complete. Our study evaluated seroprotection against tetanus among newborns in Austria, who may gain passive immunity by transplacental transfer of maternal tetanus antibody. Methods: Cord blood samples from 99 deliveries were analyzed for antibody concentration against tetanus toxoid by standardized ELISA. Results: 85/99 (85.8%) individuals presented with levels of tetanus immunity having a protective antibody concentration ≥0.1 IU/ml. 9/99 (9.1%) samples showed low seropositivity, while in 5/99 (5.1%) samples no tetanus antibodies could be detected. The median antibody concentration was 0.95 IU/ml. Conclusions: Our data provide evidence for a lack of adequate tetanus immunity in 14.2% of newborns delivered in an Austrian University Hospital. This investigation is emphasizing the importance of stringent regimens concerning prenatal vaccination care, even in countries with generalized immunization programs. If indicated, maternal immunization during pregnancy should be initiated for protection of newborns. Copyright © 2011 S. Karger AG, Basel.

Valenta R.,Christian Doppler Laboratory | Valenta R.,Center for Pathophysiology | Linhart B.,Center for Pathophysiology | Swoboda I.,Christian Doppler Laboratory | Niederberger V.,Medical University of Vienna
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

The broad applicability of allergen-specific immunotherapy for the treatment and eventually prevention of IgE-mediated allergy is limited by the poor quality and allergenic activity of natural allergen extracts that are used for the production of current allergy vaccines. Today, the genetic code of the most important allergens has been deciphered; recombinant allergens equalling their natural counterparts have been produced for diagnosis and immunotherapy, and a large panel of genetically modified allergens with reduced allergenic activity has been characterized to improve safety of immunotherapy and explore allergen-specific prevention strategies. Successful immunotherapy studies have been performed with recombinant allergens and hypoallergenic allergen derivatives and will lead to the registration of the first recombinant allergen-based vaccines in the near future. There is no doubt that recombinant allergen-based vaccination strategies will be generally applicable to most allergen sources, including respiratory, food and venom allergens and allow to produce safe allergy vaccines for the treatment of the most common forms of IgE-mediated allergies. © 2011 John Wiley & Sons A/S.

Linhart B.,Center for Pathophysiology | Valenta R.,Center for Pathophysiology | Valenta R.,Medical University of Vienna
Current Opinion in Immunology | Year: 2012

Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. © 2012 Elsevier Ltd.

Mechtcheriakova D.,Center for Pathophysiology | Svoboda M.,Center for Pathophysiology | Meshcheryakova A.,Center for Pathophysiology | Jensen-Jarolim E.,Center for Pathophysiology | Jensen-Jarolim E.,Medical University of Vienna
Cancer Immunology, Immunotherapy | Year: 2012

Activation-induced cytidine deaminase (AID) is critically involved in class switch recombination and somatic hypermutation of Ig loci resulting in diversification of antibodies repertoire and production of high-affinity antibodies and as such represents a physiological tool to introduce DNA alterations. These processes take place within germinal centers of secondary lymphoid organs. Under physiological conditions, AID is expressed predominantly in activated B lymphocytes. Because of the mutagenic and recombinogenic potential of AID, its expression and activity is tightly regulated on different levels to minimize the risk of unwanted DNA damage. However, chronic inflammation and, probably, combination of other not-yet-identified factors are able to create a microenvironment sufficient for triggering an aberrant AID expression in B cells and, importantly, in non-B-cell background. Under these circumstances, AID may target also non-Ig genes, including cancer-related genes as oncogenes, tumor suppressor genes, and genomic stability genes, and modulate both genetic and epigenetic information. Despite ongoing progress, the complete understanding of fundamental aspects is still lacking as (1) what are the crucial factors triggering an aberrant AID expression/ activity including the impact of Th2-driven inflammation and (2) to what extent may aberrant AID in human non-B cells lead to abnormal cell state associated with an increased rate of genomic alterations as point mutations, small insertions or deletions, and/or recurrent chromosomal translocations during solid tumor development and progression. © The Author(s) 2012.

Hamilton G.,Ludwig Boltzmann Cluster of Translational Oncology | Hamilton G.,Medical University of Vienna | Klameth L.,Ludwig Boltzmann Cluster of Translational Oncology | Klameth L.,Center for Pathophysiology | And 2 more authors.
Molecules | Year: 2014

Advanced small cell lung cancer (SCLC) has a dismal prognosis. Modulation of the camptothecin topotecan, approved for second-line therapy, may improve response. Our recent finding of synergistic enhancement of the cytotoxic activity of camptothecin (CPT) by cyclin-dependent kinase 4 inhibitors is extended here to a panel of camptothecin analogs comprising 10-hydroxy-CPT (HOCPT), topotecan (TPT; 9-[(dimethylamino)- methyl]-10-hydroxy-CPT), 9-amino-CPT (9AC), 9-nitrocamptothecin (rubitecan), SN38 (7-ethyl-10- hydroxycamptothecin) and 10-hydroxy-9-nitrocamptothecin (CPT109) in combination with PD0332991, CDK4I, roscovitine and olomoucine. SCLC cell lines employed are chemoresistant NCI-H417 and DMS153 and the chemosensitive SCLC26A line established at our institution. The CPT analogs exhibiting highest cytotoxicity towards the three SCLC lines tested were SN38 and 9AC, followed by rubitecan, HOCPT, TPT and CPT109. NCI-H417 and DMS153 revealed an approximately 25-fold and 7-fold higher resistance compared to the chemosensitive SCLC26A cell line. Whereas the CDK4/6 inhibitor PD0332991 proved less effective to chemosensitize SCLC cells to CPT analogs, the CDK inhibitors CDK4I, roscovitine and olomoucine gave comparable chemosensitization effects in combination with 9AC, SN38, rubitecan and to a lesser extent with TPT and CPT109, not directly related with topoisomerase mRNA expression. In conclusion, smallchemical modifications of the parent CPT structure result in differing cytotoxicities and chemomodulatory effects in combination with CDKIs of the resulting analogs. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

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