End-stage heart failure often requires heart transplantation as a life-prolonging treatment. Immunosuppressive therapy is necessary to avoid rejection, but is associated with serious adverse effects. New approaches are needed to monitor immune function in heart transplant patients.
View Article and Find Full Text PDFShort-term allograft survival has improved among solid organ transplant (SOT) patients. An increasing number of SOT patients are prepared for re-transplantation because of chronic allograft failure. Lack of HLA typing or incomplete HLA typing of previous donors complicates pretransplant risk assessment, as repeated HLA mismatches may be missed.
View Article and Find Full Text PDFHIV infects key cell types of the immune system, most notably macrophages and CD4+ T cells. Whereas macrophages represent an important viral reservoir, activated CD4+ T cells are the most permissive cell types supporting high levels of viral replication. In recent years, it has been appreciated that the innate immune system plays an important role in controlling HIV replication, e.
View Article and Find Full Text PDFCombined treatment with interferon alpha (IFN-α) and ribavirin (RBV) can effectively cure HCV infection in a significant proportion of patients, but effects of this regimen on cellular reservoirs for human immunodeficiency virus type 1 (HIV-1) are unknown. Here, we show that treatment with IFN-α/RBV led to a moderate but significant and sustained decline of HIV-1 DNA in CD4 T cells from HIV-1/hepatitis C virus-coinfected patients receiving highly active antiretroviral therapy (n = 12). However, in vitro experiments failed to demonstrate an effect of pharmacological doses of IFN-α on HIV-1 reactivation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2013
Replication of lentiviruses generates different DNA forms, including RNA:DNA hybrids, ssDNA, and dsDNA. Nucleic acids stimulate innate immune responses, and pattern recognition receptors detecting dsDNA have been identified. However, sensors for ssDNA have not been reported, and the ability of RNA:DNA hybrids to stimulate innate immune responses is controversial.
View Article and Find Full Text PDFMacrophages play an important role in human immunodeficiency virus (HIV) pathogenesis and contribute to establishment of a viral reservoir responsible for continuous virus production and virus transmission to T cells. In this study, we investigated the differences between various monocyte-derived macrophages (MDMs) generated through different differentiation protocols and evaluated different cellular, immunological, and virological properties. We found that elevated and persistent HIV-1 pWT/BaL replication could be obtained only in MDMs grown in RPMI containing macrophage colony-stimulating factor (M-CSF).
View Article and Find Full Text PDFBackground: Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate immune sensing of HIV during acute infection may contribute to failure to control and eradicate infection, persistent inflammatory responses later during infection contribute in driving chronic immune activation and development of immunodeficiency. However, knowledge on specific HIV PAMPs and cellular PRRs responsible for inducing innate immune responses remains sparse.
View Article and Find Full Text PDFMonocytes/macrophages are known to represent a potential reservoir of human immunodeficiency virus type 1 (HIV-1), which ensures continuous replication of the virus in patients on highly active antiretroviral therapy (HAART). Infected macrophages are a highly productive source of HIV-1 during infections with common opportunistic pathogens. Previous studies report that toll like receptors (TLR)s play a role in HIV-1 replication in macrophages.
View Article and Find Full Text PDFAim Of Study: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment.
Patients And Methods: A total of 44 patients received lower (n = 37), upper (n = 5), or sequential HBI (n = 2).
Background: Streptococcus pneumoniae is a human pathogenic bacteria and a major cause of severe invasive diseases, including pneumonia, bacteremia, and meningitis. Infections with S. pneumoniae evoke a strong inflammatory response, which plays a major role in the pathogenesis of pneumococcal disease.
View Article and Find Full Text PDFExcessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis.
View Article and Find Full Text PDFThis Phase I/II study investigated weekly docetaxel (Taxotere) with concurrent radiotherapy in 42 patients with untreated stage III non-small cell lung cancer (NSCLC). All patients were treated with chest irradiation: 2Gy administered 5 days/week for 5 weeks, to a total of 50Gy. Docetaxel (1-h infusion) was administered on days 1, 8, 22, and 29< or =2 h before radiation fractions 1, 6, 16, and 21 (i.
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