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Reinhard Würzner

Publications and source records attributed to Reinhard Würzner.

17 recordsLinked to original sources
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

HIV-1 and its transmembrane protein gp41 bind to different Candida species modulating adhesion.

Oral candidiasis in HIV-1-infected individuals is widely believed to be triggered by the acquired T-lymphocyte immunodeficiency. Recently, binding of the HIV-1 envelope protein gp160 and its subunit gp41, and also of the whole virus itself, to Candida albicans has been shown. The present study shows that, in addition to C. albicans, HIV-1 gp41 also binds to yeast and hyphal forms of Candida dubliniensis, a species which is closely related to C. albicans, and to Candida tropicalis but not to Candida krusei, Candida glabrata or Saccharomyces cerevisiae. The previous finding that gp41 binding to C. albicans augments fungal virulence in vitro is supported by the observation that the yeast showed an enhanced adhesion to HIV-infected H9 cells in comparison to uninfected cells. In line with these results soluble gp41 itself reduced binding of C. albicans to both endothelial and epithelial cell lines, confirming a dominant role of the gp41 binding moiety on the surface of Candida for adhesion. Surface-associated secreted aspartic proteinases (Saps) play an important role in candidial adhesion, but are not likely to be involved in the interaction as gp41 binding to the C. albicans parental wild-type strain was comparable to that of three different isogenic Sap deletion mutants. Furthermore, gp41 binding to the yeast killer toxin-susceptible C. albicans strain 10S was not inhibitable by an anti-YKT receptor antibody. In conclusion, HIV-1 interacts with different clinically important Candida spp., and may thereby affect the outcome of the respective fungal infection.

Aspartic Acid Endopeptidases↗
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

Interaction of sertraline with Candida species selectively attenuates fungal virulence in vitro.

This study investigated whether the interaction between isolates of Candida albicans (n=7), Candida parapsilosis (n=3), Candida krusei (n=2), Candida dubliniensis (n=1) and sertraline, a typical selective serotonin reuptake inhibitor, alters candidal virulence. Sertraline treatment of Candida spp. significantly (P<0.05) affected hyphal elongation, phospholipase activity, production of secreted aspartyl proteinases and fungal viability. In addition, monocyte-derived macrophages (MDMs) treated with sertraline reduced inhibition of blastoconidia germination in comparison to MDMs alone. In conclusion, our findings suggest that the interaction between sertraline and Candida spp. may also diminish the virulence properties of this fungal pathogen in vivo.

Aspartic Acid Endopeptidases↗
PubMed2003

Complement resistance mechanisms of streptococci.

Group A streptococcus (GAS, Streptococcus pyogenes), group B streptococcus (GBS, Streptococcus agalactiae) and pneumococcus (Streptococcus pneumoniae) are all human pathogens that cause significant morbidity and mortality worldwide. These related species cause different spectra of infections spanning from trivial upper respiratory tract or skin infections to septic and severe diseases. In order to cause deep infections and survive in the human body the bacteria must evade the immune system. Complement is an important part of innate immunity both as an opsonizing and membrane destructing cascade and as an effector system of antibodies. In this review, we describe the complement resistance mechanisms of the three clinically most important streptococcal species, groups A and B streptococci and pneumococcus. The complement evasion mechanisms of these three species are analogous, yet different from one another. Several strains of all three species express molecules (M-proteins, Bac or beta, PspC) that acquire host fluid-phase complement regulators factor H or C4b binding protein to their surfaces. Groups A and B streptococci also secrete proteins and/or enzymes that inhibit the activation of the complement system or chemotaxis caused by the complement activation products. Even though a lot is known about the immune evasion by streptococci, the high morbidity and mortality associated with infections caused by streptococci and the need for efficient vaccines warrant further studies on the streptococcal molecules mediating complement resistance.

Animals↗
PubMed2003

An abnormal but functionally active complement component C9 protein found in an Irish family with subtotal C9 deficiency.

Two independently segregating C9 genetic defects have previously been reported in two siblings in an Irish family with subtotal C9 deficiency. One defect would lead to an abnormal C9 protein, with replacement of a cysteine by a glycine (C98G). The second defect is a premature stop codon at amino acid 406 which would lead to a truncated C9. However, at least one of two abnormal proteins was present in the circulation of the proband at 0.2% of normal C9 concentration. In this study, the abnormal protein was shown to have a molecular weight approximately equal to that of normal C9, and to carry the binding site for monoclonal antibody (mAb) Mc42 which is known to react with an epitope at amino acid positions 412-426, distal to 406. Therefore, the subtotal C9 protein carries the C98G defect. The protein was incorporated into the terminal complement complex, and was active in haemolytic, bactericidal and lipopolysaccharide release assays. A quantitative haemolytic assay indicated even slightly greater haemolytic efficiency than normal C9. Epitope mapping with six antihuman C9 mAbs showed the abnormal protein to react to these antibodies in the same way as normal C9. However, none of these mAbs have epitopes within the lipoprotein receptor A module, where the C98G defect is located. The role of this region in C9 functionality is still unclear. In conclusion, we have shown that the lack of a cysteine led to the production of a protein present in the circulation at very much reduced levels, but which was fully functionally active.

Aged↗
PubMed2003

Importance of the terminal complement components for immune defence against Candida.

Candida activates complement via all three pathways leading to opsonisation and anaphylaxis. The aim of the study was to investigate the influence of the terminal complement system on Candida infections. Thus, fungal cell growth, mitochondrial activity and phagocytosis by polymorphonuclear leukocytes (PMNLs) as well as specific virulence factors, such as release of secreted aspartic protease (Sap) and adherence to epithelial cells, were assessed under the influence of normal or C6/C7-depleted serum. Candida (C.) dubliniensis was used in all experiments as prototype because of its known increased expression of Saps and its strong geno- and phenotypical similarity to the most abundant Candida species C. albicans. Being exposed to sufficient quantities of complement, fungal growth decreased and phagocytosis increased but mitochondrial activities of the yeast increased as well. Concerning the virulence factors, both adhesion and especially Sap release were markedly reduced in the presence of high serum concentrations. Interestingly, at low serum concentrations some opposite effects (an augmented cell growth, a higher Sap release and a stronger adhesion) were observed. In particular, it was shown that the presence of terminal complement factors, and thus the generation of the membrane attack complex, clearly induced a higher fungal mitochondrial activation and has an effect on host defence against yeast cells by augmenting phagocytosis.

Candida↗
PubMed2003

Presence of Chlamydophila psittaci DNA in the central nervous system of a patient with status epilepticus.

This study reports an extraordinarily severe and prolonged course of neuroornithosis with generalized status epilepticus as an initial symptom. Direct invasion of the central nervous system by Chlamydophila psittaci was confirmed by the demonstration of specific DNA in the patient's cerebrospinal fluid. The patient recovered slowly under administration of doxycycline.

Anti-Bacterial Agents↗
PubMed2003

Antifungal properties of 5-hydroxytryptamine (serotonin) against Candida species in vitro.

In this study the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of 5-hydroxytryptamine (5 HT, serotonin) against clinical isolates of Candida albicans (n = 11), Candida glabrata (n = 9), Candida tropicalis (n = 10) and Candida parapsilosis (ATCC 22019) using a broth microdilution test were investigated. In addition, it was examined whether delayed regrowth as a post-antifungal effect results following short exposure to 5 HT. 5 HT showed antifungal activity towards all isolates of Candida spp. The isolates yielded comparable MIC and MFC values of 5 HT in the range 0.91-7.34 mM and 1.83-14.68 mM, respectively. A lag in regrowth was dependent on the concentration tested. Treatment for 3 h at concentrations of 5 HT below and equipotent to the MFC resulted in a delayed regrowth of 8-12 h for isolates of Candida spp. In conclusion, these in vitro studies clearly demonstrate antifungal effects of 5 HT. Identifying the mode of action could be of great help in developing and researching new antifungal drugs.

Antifungal Agents↗
PubMed2003

Antibody-dependent killing of meningococci by human neutrophils in serum of late complement component-deficient patients.

BACKGROUND: Thirty-one Russian patients with late complement component deficiency (LCCD) who had experienced one to five meningococcal infections were immunized with meningococcal polysaccharide vaccine (A + C + W135 + Y) and were followed for 3-8 years. We investigated the potentially protective killing effect of human neutrophils (PMNL) on serogroup A and W135 meningococci. METHODS: Meningococci were incubated in LCCD vaccine sera in the absence or presence of PMNL, and the number of live bacteria (CFU) was determined by plating onto chocolate agar. RESULTS: When meningococci were incubated in the LCCD sera alone, exponential growth of meningococci occurred despite the presence of meningococcal antibodies. After the addition of PMNL, meningococci were inhibited in their growth or even eliminated. Group A or W135 meningococci were killed effectively by PMNL in 80% of the sera which were collected 1 month to 1 year after vaccination compared to only 40% in the prevaccination LCCD sera (p < 0.05). Three years after vaccination 67% of the LCCD sera were still capable of promoting killing (and even 90% after revaccination). The rate of killing correlated with the concentration of serogroup-specific immunoglobulins. In 83% of the 72 LCCD sera with more than 5 microg/ml anti-group A immunoglobulins the killing of group A meningococci was promoted. By contrast, only 21% of 19 samples with lower specific antibody levels showed a PMNL-mediated meningococcal killing (p < 0.05). The same effect was observed for group W135 meningococci. CONCLUSION: PMNL kill meningococci during incubation in LCCD serum; this effect increases after vaccination and depends on both specific antibody and complement. Protection by vaccination may therefore be caused by an increased killing capacity of PMNL.

Adolescent↗
PubMed2002

A technique for isolation of rubella virus-like particles by sucrose gradient ultracentrifugation using Coomassie brilliant blue G crystals.

An improved method for the isolation of rubella virus-like particles (RVLP) from cell culture supernatant of transfected Chinese hamster ovary (CHO24S) cells is described. It employs a combination of membrane filtration with sucrose gradient ultracentrifugation. It was found that staining the RVLP band with Coomassie brilliant blue G (CBB) resulted in the CBB crystals adsorbing RVLP. After ultracentrifugation (25,000 rpm, 3h, 4 degrees C) a sharp blue band with crystals (diameter 30-40 microm) was observed (at a density of 1.250 g/ml at 25 degrees C) in a 30-60% sucrose gradient. Using a combination of SDS-PAGE and Western blotting techniques, E1 rubella virus structural protein was detected only in the solutions derived from the sharp blue band. A decrease in crystal concentration a few millimeters above or below the main band was associated with a decrease in protein concentration. By dilution with a saturated ice-cold 30% sucrose solution it was possible to pellet the crystals by centrifugation (15,000 rpm, 10 min). SDS-PAGE showed a much higher concentration of RVLP structural protein in the pellet than in the supernatant. This RVLP-containing material is especially suitable for the preparation of rubella virus immunoblot stripes.

Animals↗
PubMed2002

Impact of N-chlorotaurine on viability and production of secreted aspartyl proteinases of Candida spp.

N-Chlorotaurine, an endogenous long-lived oxidant, demonstrated fungicidal activity against Candida spp. and a postantifungal effect. Secreted aspartyl proteinases, important fungal virulence factors, proved to be a first target of impact. These results provide support for the topical application of N-chlorotaurine as an antimicrobial agent in yeast infections.

Aspartic Acid Endopeptidases↗
PubMed2002

Mechanism of human immunodeficiency virus-induced complement expression in astrocytes and neurons.

The cerebral complement system is hypothesized to contribute to neurodegeneration in the pathogenesis of AIDS-associated neurological disorders. Our former results have shown that the human immunodeficiency virus (HIV) strongly induces the synthesis of complement factor C3 in astrocytes. This upregulation explains in vivo data showing elevated complement levels in the cerebrospinal fluid of patients with AIDS-associated neurological symptoms. Since inhibition of complement synthesis and activation in the brain may represent a putative therapeutic goal to prevent virus-induced damage, we analyzed in detail the mechanisms of HIV-induced modulation of C3 expression. HIV-1 increased the C3 levels in astrocyte culture supernatants from 30 to up to 400 ng/ml; signal transduction studies revealed that adenylate cyclase activation with upregulation of cyclic AMP is the central signaling pathway to mediate that increase. Furthermore, activity of protein kinase C is necessary for HIV induction of C3, since inhibition of protein kinase C by prolonged exposure to the phorbol ester tetradecanoyl phorbol acetate partly abolished the HIV effect. The cytokines tumor necrosis factor alpha and gamma interferon were not involved in mediating the HIV-induced C3 upregulation, since neutralizing antibodies had no effect. Besides whole HIV virions, the purified viral proteins Nef and gp41 are biologically active in upregulating C3, whereas Tat, gp120, and gp160 were not able to modulate C3 synthesis. Further experiments revealed that neurons were also able to respond on incubation with HIV with increased C3 synthesis, although the precise pattern was slightly different from that in astrocytes. This strengthens the hypothesis that HIV-induced complement synthesis represents an important mechanism for the pathogenesis of AIDS in the brain.

Adenylyl Cyclases↗
PubMed2001

Circulating cytotoxic CD8(+) CD28(-) T cells in ankylosing spondylitis.

Circulating CD8(+) CD28(-) T cells were found to be expanded more in patients with ankylosing spondylitis than in an age-matched healthy population (41.2 +/- 17.7% versus 18.6 +/- 7.6%). The level of CD8(+)CD28(-) T cells was dependent on the disease status, but was independent of age. Most of the CD8(+) CD28(-) T cells produced perforin after stimulation in vitro, in contrast to their CD8(+)CD28(+) counterparts. From the clinical perspective, the percentage of the cytotoxic CD8(+) CD28(-) T cells reflected a more severe course of disease, as it correlated with distinct movement restrictions, as well as the metrology score summarizing cervical rotation (in sitting position), chin-to-jugulum distance, thoracic Schober, chest expansion, and fingers-to-floor distance (P = 0.032).

CD28 Antigens↗
PubMed2000

Borreliacidal activity of early Lyme disease sera against complement-resistant Borrelia afzelii FEM1 wild-type and an OspC-lacking FEM1 variant.

Sera obtained from 14 Lyme borreliosis patients at early stages (stages I and II) of the disease were examined for their borreliacidal properties against Borrelia afzelii isolate FEM1 by use of a growth inhibition assay. Five of 14 immune sera exhibited borreliacidal activity against isolate FEM1. Heat-inactivated immune sera failed to kill the spirochaetes. Immunoblotting experiments with outer-membrane preparations showed that OspC and 11 additional proteins of 14.0, 16.0, 17.7, 19.3, 21.7, 27.5, 32.7, 40.7, 48.9, 51.3 and 53.6 kDa were recognised by borreliacidal immune sera. To analyse the borreliacidal properties of anti-OspC antibodies, two sera (EM4 and EM5), which beside antibodies against a 51.3-kDa protein contained exclusively anti-OspC antibodies, were further investigated by comparative analysis with a FEM1 wild-type and a FEM1 variant lacking OspC in a growth inhibition assay. Only FEM1 wild-type and not variant FEM1OspC(-) was killed by immune sera EM4 and EM5. Complement-dependent killing of FEM1 wild-type was mediated by formation of the terminal complement complex that was found to be attached directly to the outer membrane as confirmed by immuno-electron microscopy. No complement deposition was observed on the surface of variant FEM1OspC(-) after incubation with immune sera EM4 and EM5, thereby suggesting that only anti-OspC antibodies in these two immune sera were responsible for borreliacidal activity. These results provide direct evidence that anti-OspC antibodies, once developed during the immune response, are of critical importance for efficient killing of borreliae in the early phase of infection.

Antibodies, Bacterial↗