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  • Doerr, Hans  (18)
  • Cinatl, J.
  • Springer (CrossRef)  (18)
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  • 1
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.181-190
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. This first part concentrates on epidemiologic concerns and virulence determinants. H5N1 spread over the world and caused a series of fowl pest outbreaks. Significant human-to-human transmissions have not been observed yet. Mutations that make the virus more compatible with human-to-human transmission may occur at any time. Nevertheless, no one can currently predict with certainty whether H5N1 will become a human pandemic virus.
    Keywords: Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 2
    Language: English
    In: Cellular and Molecular Life Sciences, 2011, Vol.68(6), pp.1079-1090
    Description: Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
    Keywords: Human cytomegalovirus ; Sorafenib ; Kinase inhibitor ; Raf ; Immediate early antigen ; Cancer chemotherapy ; Oncomodulation ; Antiviral therapy
    ISSN: 1420-682X
    E-ISSN: 1420-9071
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  • 3
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 4
    Language: English
    In: Medical Microbiology and Immunology, 2013, Vol.202(1), pp.37-47
    Description: Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.
    Keywords: Cytomegalovirus ; Viral tropism and virulence ; Retinitis ; AIDS
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 5
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.191-201
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. The second part focuses on experimental and clinical results, which give insights in the pathogenic mechanisms of H5N1 infection in humans. H5N1 is poorly transmitted to humans. However, H5N1-induced disease is very severe. More information on the role entry barriers, H5N1 target cells and on H5N1-induced modulation of the host immune response is needed to learn more about the determinants of H5N1 pathogenicity.
    Keywords: Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.203-212
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 as well as treatment options are discussed. The third part discusses therapeutic options. Neuraminidase (NA) inhibitors are the most promising agents despite uncertainty about efficacy. Dosage increase, prolonged treatment or combination therapies may increase treatment efficacy and/or inhibit resistance formation. Immune system dysregulation contributes to H5N1 disease. Although current evidence does not support the use of anti-inflammatory drugs beneficial effects cannot be excluded at later disease stages.
    Keywords: Antiviral Agents ; Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(4), pp.291-297
    Description: Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8 + T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Glycyrrhizin ; H5N1 ; Cytokines ; Monocyte-derived macrophages
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 8
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(2), pp.93-101
    Description: Tumor resistance to lysis by resting natural killer (NK) cells may be overcome by priming of NK cells with cytokines or by binding of NK activating receptors to ligands expressed on target cells. In this study, major histocompatibility complex class I (MHC-I)-negative LNCaP and MHC-I-positive DU145 cells were infected with genetically modified influenza A virus lacking the non-structural gene 1 (∆NS1 IAV). The cells were used to investigate the influence of ∆NS1 IAV infection on NK cell lysis of tumor cells as well as to prime NK cells for lysis of LNCaP and DU145 cells. While LNCaP cells infected with ΔNS1 IAV showed enhanced lysis when compared with mock-infected cells (93% ± 1.47 vs. 52% ± 0.74), both mock-infected and ΔNS1 IAV-infected DU145 cells were resistant to NK cell lysis. Moreover, NK cells primed with ΔNS1 IAV-infected LNCaP/DU145 cells effectively lysed resistant DU145 and sensitive LNCaP cells to a greater extent than NK cells primed with mock-infected LNCaP/DU145 or non-primed NK cells. Also, NK cell priming with ΔNS1 IAV-infected tumor cells enhanced extracellular signal-regulated kinase phosphorylation and increased granule release in NK cells. The increased granule release was specifically mediated by NKp46, which eventually potentiated NK cells primed with ΔNS1 IAV-infected tumor cells to overcome the inhibitory effects posed by MHC-I expression on DU145 cells. These findings show that in addition to direct lytic activity of NK cells, ΔNS1 IAV may influence anti-tumoral responses by priming NK cells.
    Keywords: Cytotoxicity ; NK cell priming ; Major histocompatibility complex class I ; Degranulation ; Oncolytic influenza A virus
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 9
    Language: English
    In: Medical Microbiology and Immunology, 2009, Vol.198(2), pp.79-81
    Description: The (possible) relationship between HCMV and cancer has been discussed for decades. Detection of viral DNA, mRNA and/or antigens in tumour tissues as well as seroepidemiologic evidence suggested a role of HCMV infection in several human malignancies. However, controversial clinical results from diVerent groups had raised skepticism about a role of HCMV in cancer.
    Keywords: Cytomegalovirus–Physiology ; Cytomegalovirus Infections–Complications ; Humans–Etiology ; Neoplasms–Virology ; Neoplasms–Virology ; Infections ; Viruses ; Cancer ; Pathology;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 10
    Language: English
    In: Medical Microbiology and Immunology, 2009, Vol.198(3), pp.175-183
    Description: Influenza A viruses represent a continuous pandemic threat. In April 2009, a novel influenza A virus, the so-called swine-origin influenza A (H1N1) virus (S-OIV), was identified in Mexico. Although S-OIV originates from triple-reassortant swine influenza A (H1) that has been circulating in North American pig herds since the end of the 1990s, S-OIV is readily transmitted between humans but is not epidemic in pigs. After its discovery, S-OIV rapidly spread throughout the world within few weeks. In this review, we sum up the current situation and put it into the context of the current state of knowledge of influenza and influenza pandemics. Some indications suggest that a pandemic may be mild but even “mild” pandemics can result in millions of deaths. However, no reasonable forecasts how this pandemic may develop can be made at this time. Despite stockpiling by many countries and WHO, antiviral drugs will be limited in case of pandemic and resistances may emerge. Effective vaccines are regarded to be crucial for the control of influenza pandemics. However, production capacities are restricted and development/production of a S-OIV vaccine will interfere with manufacturing of seasonal influenza vaccines. The authors are convinced that S-OIV should be taken seriously as pandemic threat and underestimation of the menace by S-OIV to be by far more dangerous than its overestimation.
    Keywords: Swine influenza ; H1N1 ; Swine-origin influenza A (H1N1) virus ; Pandemic
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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