Sillo P.,Semmelweis University |
Pinter D.,Semmelweis University |
Ostorhazi E.,Semmelweis University |
Mazan M.,Hungarian Academy of Sciences |
And 9 more authors.
Journal of Clinical Microbiology | Year: 2012
Eosinophilic fasciitis (EF) with generalized sclerodermiform skin lesions developed over a 19-month period in a previously healthy 23-year-old man. Although we confirmed EF by skin histology and laboratory tests, the recurrent fevers and the clinical observation of sclerotic prepuce with urethritis indicated further bacteriological analysis by conventional microbiological and DNA-based tests. Urethra cultures were positive for an arginine-hydrolyzing mycoplasma and Ureaplasma urealyticum. The patient also had serum IgM antibodies to Mycoplasma pneumoniae using enzyme-linked immunosorbent assay (ELISA)-based qualitative detection. Mycoplasma arginini was isolated from two independent venous blood serum samples and was identified by conventional microbiological tests and sequencing of the 16S rRNA and rpoB genes (GenBank sequence accession numbers HM179555 and HM179556, respectively). M. arginini genomic DNA also was detected by species-specific PCR in the skin lesion biopsy sample. Treatment with corticosteroids and long-term courses of selected antibiotics led to remission of skin symptoms and normalization of laboratory values. This report provides the first evidence of EF associated with mycoplasma infection and the second report of human infection with M. arginini and therefore suggests that this mycoplasma infection might have contributed to the pathogenesis of the disease. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Nemeth G.,Vichem Chemie Research Ltd. |
Nemeth G.,Semmelweis University |
Varga Z.,Vichem Chemie Research Ltd. |
Varga Z.,Semmelweis University |
And 17 more authors.
Current Medicinal Chemistry | Year: 2011
Cyclin Dependent Kinases (CDKs) are important regulators of cell cycle and gene expression. Since an up-todate review about the pharmacological inhibitors of CDK family (CDK1-10) is not available; therefore in the present paper we briefly summarize the most relevant inhibitors and point out the low number of selective inhibitors. Among CDKs, CDK9 is a validated pathological target in HIV infection, inflammation and cardiac hypertrophy; however selective CDK9 inhibitors are still not available. We present a selective inhibitor family of CDK9 based on the 4-phenylamino-6- phenylpyrimidine nucleus. We show a convenient synthetic method to prepare a useful intermediate and its derivatisation resulting in novel compounds. The CDK9 inhibitory activity of the derivatives was measured in specific kinase assay and the CDK inhibitory profile of the best ones (IC50 < 100nM) was determined. The most selective compounds had high selectivity over CDK1, 2, 3, 5, 6, 7 and showed at least one order of magnitude higher inhibitory activity over CDK4 inhibition. The most selective molecules were examined in cytotoxicity assays and their ability to inhibit HIV-1 replication was determined in cellular assays. © 2011 Bentham Science Publishers Ltd.
Nemeth G.,Vichem Chemie Ltd. |
Greff Z.,Vichem Chemie Ltd. |
Sipos A.,Vichem Chemie Ltd. |
Varga Z.,Vichem Chemie Ltd. |
And 18 more authors.
Journal of Medicinal Chemistry | Year: 2014
Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate, and phosphinate moieties were synthesized. Prepared compounds were evaluated in an enzymatic CDK9/CycT1 assay. The most potent molecules were tested in cell-based toxicity and HIV proliferation assays. Selectivity of shortlisted compounds against CDKs and other kinases was tested. The best compound was shown to be a highly specific, ATP-competitive inhibitor of CDK9/CycT1 with antiviral activity. © 2014 American Chemical Society.
Sollner J.,Emergentec Biodevelopment GmbH |
Heinzel A.,Emergentec Biodevelopment GmbH |
Heinzel A.,Upper Austria University of Applied Sciences |
Summer G.,Upper Austria University of Applied Sciences |
And 6 more authors.
Immunome Research | Year: 2010
Background. The last years have seen a renaissance of the vaccine area, driven by clinical needs in infectious diseases but also chronic diseases such as cancer and autoimmune disorders. Equally important are technological improvements involving nano-scale delivery platforms as well as third generation adjuvants. In parallel immunoinformatics routines have reached essential maturity for supporting central aspects in vaccinology going beyond prediction of antigenic determinants. On this basis computational vaccinology has emerged as a discipline aimed at ab-initio rational vaccine design. Here we present a computational workflow for implementing computational vaccinology covering aspects from vaccine target identification to functional characterization and epitope selection supported by a Systems Biology assessment of central aspects in host-pathogen interaction. We exemplify the procedures for Epstein Barr Virus (EBV), a clinically relevant pathogen causing chronic infection and suspected of triggering malignancies and autoimmune disorders. Results. We introduce pBone/pView as a computational workflow supporting design and execution of immunoinformatics workflow modules, additionally involving aspects of results visualization, knowledge sharing and re-use. Specific elements of the workflow involve identification of vaccine targets in the realm of a Systems Biology assessment of host-pathogen interaction for identifying functionally relevant targets, as well as various methodologies for delineating B- and T-cell epitopes with particular emphasis on broad coverage of viral isolates as well as MHC alleles. Applying the workflow on EBV specifically proposes sequences from the viral proteins LMP2, EBNA2 and BALF4 as vaccine targets holding specific B- and T-cell epitopes promising broad strain and allele coverage. Conclusion. Based on advancements in the experimental assessment of genomes, transcriptomes and proteomes for both, pathogen and (human) host, the fundaments for rational design of vaccines have been laid out. In parallel, immunoinformatics modules have been designed and successfully applied for supporting specific aspects in vaccine design. Joining these advancements, further complemented by novel vaccine formulation and delivery aspects, have paved the way for implementing computational vaccinology for rational vaccine design tackling presently unmet vaccine challenges. © 2010 Söllner et al.
Rajcani J.,Slovak Academy of Sciences |
Rajcani J.,RT Europe Nonprofit Ltd. |
Asvanyi-Molnar N.,RT Europe Nonprofit Ltd. |
Szathmary S.,Galenbio Ltd
Acta Microbiologica et Immunologica Hungarica | Year: 2010
Lymphomas are solid tumors consisting of lymphoid cells; they form a heterogeneous group of less or more malignant disorders. A portion of lymphomas develop due to latent herpesvirus infections established in B and/or T-lymphocytes. The basis for latency is a lifelong presence of the circularized covalently linked viral genome within nuclei of carrier lymphocytes. In certain cases, however, the essential event leading to tumor formation is the integration of a portion(s) of viral DNA into the host cell DNA. This leads to rearrangements within the host cell genome on one hand, and, on other hand, to unregulated expression of oncoproteins encoded by the integrated fragment. Our review deals with mechanisms of lymphoma formation regarding to the role of non-structural herpesvirus oncoproteins interfering with the regulation of cell division and/or exerting anti-apoptotic effects. In addition, the authors wish to highlight the common procedures, which allowed isolation and/or identification of lymphoma-associated viruses in cell cultures derived from tumors and/or proliferating lymphatic tissues. © 2010 Akadémiai Kiadó, Budapest.
Stipkovits L.,Carlsbad Research Organization |
Stipkovits L.,Europe Research Center |
Somogyi M.,Europe Research Center |
Somogyi M.,GalenBio Kft |
And 5 more authors.
Journal of Dairy Science | Year: 2013
We performed a comparative study on the development of mastitis induced by Mycoplasma arginini or Streptococcus dysgalactiae after challenging the cows. Mycoplasma arginini did not cause any clinical symptoms on its own, resulting in only a transient increase of somatic cell count (SCC; increase ranging from 0.5×106 to 0.8×106 cells/mL) and a slight decrease of milk production (10%) for 5 d. In contrast, Strep. dysgalactiae induced more severe clinical signs in animals and SCC increased to 1.60×106 to 2.11×106 cells/mL for 10 d. In addition, milk production decreased (22.9 to 27.0%) for 10 d. After 3mo (2mo after the first challenge), animals that were challenged previously with M. arginini were rechallenged with Strep. dysgalactiae. Severe clinical mastitis developed, with very high SCC (5.00×106 to 21.5×106 cells/mL), and a very significant reduction of milk production (28.6 to 68.7%), which lasted more than 4wk, was observed. The severe clinical mastitis developed not only in cows inoculated with Strep. dysgalactiae andM. arginini in the same udder quarter but also in cows infected in the quarter previously not challenged with mycoplasma. Cows challenged first with Strep. dysgalactiae and rechallenged with M. arginini 2mo later developed only slight changes in both SCC and milk production, similar to those when the cows were challenged with M. arginini alone. We conclude that M. arginini infection does not cause remarkable mastitis (characterized by decrease in milk production and increase of SCC) but it significantly predisposes animals to infection with Strep. dysgalactiae, leading to severe clinical mastitis. © 2013 American Dairy Science Association.
Stipkovits L.,Europe Research Center |
Szathmary S.,Europe Research Center |
Szathmary S.,Galen Bio Inc.
Poultry Science | Year: 2012
Production of ducks and geese in certain parts of the world is very important. Mycoplasma diseases cause significant losses to the duck and goose industry. This review summarizes the epidemiological, clinical, and pathomorphological characteristics of mycoplasma diseases of ducks and geese and the involvement of the various mycoplasma species in their pathogenesis. The role of mycoplasma infections in the development of clinical signs, pathological lesions, and mortality of challenged birds is demonstrated in challenge experiments. Transmission of mycoplasma in the ovary and eggs resulting in the reduction of egg production and an increase of embryo mortality has been shown in challenge experiments as well as in field studies. The susceptibility of many mycoplasma isolates of the most important mycoplasma species of duck and goose origin were tested and showed relatively high average minimum inhibitory concentrations of lincomycin, tilosin, oxytetracycline, chlortetracycline, and enrofloxacin but not for tiamulin. The successful treatment of mycoplasma infections with antibiotics in ducks and geese should be selected based on the minimum inhibitory concentration values against the mycoplasmas isolated from the flock. © 2012 Poultry Science Association Inc.
GalenBio Inc. | Date: 2015-08-24
This invention provides a microparticle carrier system comprising of one or more proteins, peptides, nucleic acids, carbohydrates, lipids or other bioactive substances with or without targeting molecules attached. In addition, the invention also provides immune modulatory compositions and methods of eliciting protective immune responses both in uninfected and infected hosts as well as the induction of immune tolerance.