Biomedical subjects

Barbara Falkensammer

Publications and source records attributed to Barbara Falkensammer.

8 recordsLinked to original sources

PubMed2007

A single vaccination with attenuated SIVmac 239 via the tonsillar route confers partial protection against challenge with SIVmac 251 at a distant mucosal site, the rectum.

Elucidating the mechanisms that protect monkeys previously immunized with attenuated SIV (SIVDeltanef) against challenge infection with pathogenic virus may reveal new strategies for the development of an effective HIV vaccine. Here we show that a single atraumatic application of SIVDeltanef to the tonsils of four rhesus macaques conferred protection against SIVmac251 applied intrarectally 26 weeks later. While this protection was not complete, i.e., challenge virus could be isolated from all immunized animals, it was reflected by significantly lower viral loads in the blood (weeks 2-16 after challenge, p < 0.01) and considerably lower loads in lymphoid organs, and more stable peripheral CD4 counts in a proportion of the immunized animals as compared to four non-immunized, SIVmac251-infected control monkeys. SIV-specific humoral as well as systemic and mucosal T cell responses were detected in the immunized animals, but there was no correlation between their magnitude of expression and the level of protection. Analyses of leukocyte subsets in these animals at necropsy (24 weeks after challenge) did not reveal a significantly enhanced proportion of gamma/delta T cells in the tissues of protected monkeys. Therefore, tonsillar application of attenuated SIV induces protection in some animals against a superinfection with wild-type SIV distant at a distant mucosal site.

Animals↗

PubMed2007

Changes in HIV-specific antibody responses and neutralization titers in patients under ART.

In this study, we tested for antibody reactivities against gp120 and gp41-derived peptides, recombinant gp160, gp41 and tat in HIV-positive sera under antiretroviral therapy (ART) and determined their neutralization capacity. As a baseline, sera from patients in stage A, B and C of the disease, long term non-progressors (LNPs) and HIV-negative individuals were included. Compared to LNPs or sera from patients in group A, the reactivity of sera in stage B or C against gp120-derived peptides was reduced parallel to disease progression. Reactivity of these samples was compared with sera of patients under ART. Parallel to the decrease of viral load, the reactivity against gp120 and gp41-derived epitopes, recombinant gp160 and gp41 or the native gp120/41 complex was significantly reduced. Antibody-mediated neutralization of HIV-1 was detectable prior to ART but revealed substantial decreases coupled with progression of therapy. Responses to recombinant tat dropped after three months of therapy, increased however at later time points to initial levels. These data indicate that in parallel to the decrease in viral load and antibodies against gp120, the neutralization capacity of sera under ART is reduced, and can not be compensated by an increase in tat-specific antibodies.

Antibodies, Viral↗

PubMed2006

Human granulocytic anaplasmosis in Austria: epidemiological, clinical, and laboratory findings in five consecutive patients from Tyrol, Austria.

We report five consecutive cases of Anaplasma (A.) phagocytophilum infection (the causative agent of human granulocytic anaplasmosis (HGA)) from western Austria. All infections were acquired between June and August in 2003 and 2004 in the Inn valley (Tyrol, Austria). Four patients required hospitalisation, one patient was treated as an outpatient. During the acute stage of illness, laboratory findings included thrombocytopenia (5/5), elevated C-reactive protein (5/5), elevated neopterin (5/5), elevated lactate dehydrogenase (4/5), and elevation of liver enzymes (4/5). Leukopenia (3/5) and elevated procalcitonin (2/5) were less frequently observed. All patients were treated with tetracyclines, which led to prompt improvement of the clinical conditions. Anti-platelet antibodies were observed in one of four patients, but remained unchanged after complete covalescence.

Adult↗

PubMed2005

Complement dependent trapping of infectious HIV in human lymphoid tissues.

OBJECTIVES: HIV-1 bound extracellularly to follicular dendritic cells (FDC) in germinal centers (GC) of lymphoid tissues (LT) represents the largest viral reservoir in HIV-infected individuals; however there is no direct evidence as to whether HIV trapped in human GC remains infectious. In the GC, complement receptors and Fc gamma receptors have been suggested to participate in trapping of HIV; therefore, the relative contribution of complement- and Fc gamma receptors in binding HIV on LT was investigated and the infectivity of this virus was tested. DESIGN: As it is difficult to isolate FDC without contaminations of productively infected cells, HIV was detached from LT of HIV positive individuals using antibodies blocking complement- and Fc gamma receptors. Isolated virus was tested in an infectivity assay. METHODS: HIV detached from LT was quantified by HIV p24 ELISA, PCR and in an in vitro infectivity assay. Presence and accessibility of viral envelope proteins, complement factors and immunoglobulins on the surface of detached viral particles were evaluated through viral capture by respective antibodies. RESULTS: Although both C3d-fragments and IgG molecules were identified on the surface of HIV detached from LT, trapping of HIV was mediated solely by CR2-C3d interactions, whereas contribution of Fc gamma receptors was not detectable. Infectivity assays with HIV stripped from LT of HIV positive individuals revealed that in four out of ten patients HIV particles were infectious. CONCLUSIONS: These findings indicate that in the GC infectious virus is trapped on CR2-expressing FDC (or B cells). Reduction of this pool of HIV could be a therapeutic goal.

Cells, Cultured↗

PubMed2003

Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28- T cells in ankylosing spondylitis.

Circulating CD3+CD4+CD28- cells exhibit reduced apoptosis and were found to be more enriched in patients with ankylosing spondylitis than in age-matched healthy control individuals (7.40 +/- 6.6% versus 1.03 +/- 1.0%; P < 0.001). Levels of CD4+CD28- T cells correlate with disease status as measured using a modified metrology score, but they are independent of age and duration of ankylosing spondylitis. CD4+CD28- T cells produce IFN-gamma and perforin, and thus they must be considered proinflammatory and cytotoxic. These T cells share phenotypic and functional properties of natural killer cells, strongly expressing CD57 but lacking the lymphocyte marker CD7. MHC class I recognizing and activating natural killer cell receptors on the surface of CD4+CD28- T cells may be involved in a HLA-B27 mediated co-stimulation of these proinflammatory and cytotoxic cells.

Apoptosis↗

PubMed2003

First documented case of human granulocytic ehrlichiosis in Austria.

We report the first documented case of human granulocytic ehrlichiosis (HGE) in Austria. The infection was acquired near Arzl in the surroundings of Innsbruck in northern Tyrol. Except for a biphasic course of illness, presentation in this 33-year-old female patient was comparable to clinical findings observed in other European adults with high fever, transient thrombocytopenia, elevated levels of CRP and LDH, arthralgias, myalgias, fatigue and subfebrile temperature. Flu-like symptoms started about seven days after a tick bite and lasted for ten days, followed by an asymptomatic interval of three days and an acute onset of fever up to 39.5 degrees C on day 20. On admission, the patient showed high antibody titres against Anaplasma phagocytophilum (IgG 1:1024, IgM 1:640); six weeks later the IgG-titre had risen to 1:2048, and IgM-levels had fallen below 1:40. The demonstration of anti-platelet antibodies in acute-phase serum was noteworthy. We conclude that also in Austria HGE should be considered in patients with febrile thrombocytopenia, especially when the medical history reveals recent tick exposure.

Adult↗

PubMed2003

Simultaneous separation of fifteen approved protease and reverse transcriptase inhibitors for human immunodeficiency virus therapy by capillary electrophoresis.

In the present investigation, a novel approach towards a complete separation of all 15 protease and reverse transcriptase inhibitors which are currently approved for use in highly active antiretroviral therapy in a single analytical run is presented. The developed method employs an acidic background electrolyte with sodium polyanethol sulfonate (SPAS) as polyanionic electroosmotic flow (EOF) modifier to establish a strong cathodic EOF, sodium dodecyl sulfate (SDS) as pseudostationary selector, and acetonitrile and ethanol as organic modifiers. Separation of the analytes is based on two different mechanisms. The more basic analytes are protonated at the prevailing pH conditions and thus migrate in front of the cathodic EOF, whereas the less basic and neutral analytes interact with the SDS and are retained after the EOF. By optimizing electrolyte pH, the amount of solvents and SDS concentrations in the background electrolyte it is possible to completely separate all compounds of interest.

Electrophoresis, Capillary↗

PubMed2002

Complement receptors in HIV infection.

Similar to other pathogens, HIV can directly activate the complement pathway even in the absence of antibodies. During and after seroconversion, HIV-specific antibodies enhance the activation of complement and increase deposition of complement fragments on virions dramatically. However, even in the presence of HIV-specific antibodies, no or only poor lysis occurs. HIV has adapted different protection mechanisms to keep complement activation under the threshold necessary to induce virolysis. In addition to its own envelope proteins, the viral envelope contains membrane-anchored host molecules. Among those are complement regulatory proteins that remain functionally active on the surface of HIV and turn down the complement cascade. In addition, serum proteins with complement regulatory activities become secondarily attached onto the virus, thereby enhancing the protection of HIV against complement-mediated damage. Therefore, opsonised virions accumulate in HIV-infected individuals, which subsequently interact with complement receptor (CR) expressing cells. This review is mainly focused on these interactions, which result either in infection of CR-positive cells with high efficiency, or retention of viral particles on their surface via CRs, thereby promoting transmission of virus to other permissive cells.

Animals↗