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Biomedical subjects

Manfred P Dierich

Publications and source records attributed to Manfred P Dierich.

At least 19 recordsLinked to original sources
PubMed2007

Immune response to retroviral infections of the brain.

Various neurological manifestations of retroviral infections have been reported, including peripheral neuropathy, encephalopathy and neuronal degeneration. After penetration into the central nervous system (CNS) the invading retroviruses meet a unique immunological situation that differs significantly from that in the periphery. Due to the blood-brain barrier with its general access restrictions peripheral T-cells, monocytes and B-cells are only "guests" in the brain; instead the immune balance is shifted in favour of the local innate immunity with microglia, astrocytes, cytokines/chemokines and complement forming the dominating defence network. The present article focuses on the most important retroviral infections and highlights the immunological aspects of the neuropathogenesis induced by selected retroviruses. These aspects include: (i) local and infiltrated immune cells as targets of retroviral infection; (ii) stimulation of the cerebral immunity network by retroviruses and subsequent steps of antiviral defence; and (iii) immune activation products as potential contributors to neural damage in the sensitive brain tissue.

Animals↗
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

Co-infection with two Chlamydophila species in a case of fulminant myocarditis.

OBJECTIVE: The aim of this study is to describe a case of fulminant myocarditis caused by co-infection with Chlamydophila pneumoniae and Chlamydophila psittaci in order to facilitate diagnosis and clinical management of patients suffering from this rare but life-threatening condition. DESIGN: Case report. SETTING: Intensive care unit of Innsbruck Medical University. PATIENT: A 24-yr-old patient admitted with septicemia and cardiac failure. INTERVENTIONS: Cardiopulmonary resuscitation, extracorporal membrane oxygenation, implantation of an extracorporal cardiac assist device, and antibiotic treatment with erythromycin. MEASUREMENTS AND MAIN RESULTS: Cp. pneumoniae and Cp. psittaci were identified by means of polymerase chain reaction and electron microscopy in the patient's myocytes. Successful weaning off the ventricular assist device was performed within 2 wks after commencement of antibiotic therapy. CONCLUSIONS: This case report demonstrates co-infection with Cp. pneumoniae and Cp. psittaci to be a hitherto unknown cause of fulminant myocarditis. There is a particular risk of misdiagnosis of viral myocarditis, which must be avoided. Patients should be transferred to a center where extracorporal membrane oxygenation therapy and molecular diagnosis of all members of the family Chlamydiaceae are available.

Adult↗
PubMed2006

Posaconazole enhances the activity of amphotericin B against Aspergillus hyphae in vitro.

The MICs and fractional inhibitory concentrations of posaconazole (POS) and voriconazole (VRZ), alone and in combination with amphotericin B (AMB), for the conidia and hyphae of 100 Aspergillus isolates were evaluated. POS-AMB had more synergistic activity against hyphae (75% of isolates) than VRZ-AMB (37%) and significantly more synergistic activity against hyphae than against conidia (12%).

Amphotericin B↗
PubMed2006

Emerging Shiga toxin-producing Escherichia coli serotypes in Europe: O100:H- and O127:H40.

Novel and as yet rare non-O157 Shiga toxin (Stx)-producing Escherichia coli (STEC) serotypes are emerging in Europe. Two different sorbitol-fermenting STECs, O100:H- carrying the virulence gene stx2 and O127:H40 carrying stx1 and eae genes (found in two related subjects), were isolated from patients' stool samples. Non-O157 STEC infections in humans are currently under-diagnosed. This report highlights the need for, and importance of, screening for Shiga toxins or serotypes other than just O157.

Aged↗
PubMed2006

Factor I-mediated processing of complement fragments on HIV immune complexes targets HIV to CR2-expressing B cells and facilitates B cell-mediated transmission of opsonized HIV to T cells.

Our study demonstrates that binding of complement-opsonized HIV to complement receptor type 1 on human erythrocytes (E) via C3b fragments is followed by a rapid normal human serum-mediated detachment of HIV from E. The release was dependent on the presence of factor I indicating a conversion of C3b fragments to iC3b and C3d on the viral surface. This in turn resulted in an efficient binding of opsonized HIV to CR2-expressing B cells, thus facilitating B cell-mediated transmission of HIV to T cells. These data provide a new dynamic view of complement opsonization of HIV, suggesting that association of virus with E might be a transient phenomenon and the factor I-mediated processing of C3b to iC3b and C3d on HIV targets the virus to complement receptor type 2-expressing cells. Thus, factor I in concert with CR1 on E and factor H in serum due to their cofactor activity are likely to be important contributors for the generation of C3d-opsonized infectious HIV reservoirs on follicular dendritic cells and/or B cells in HIV-infected individuals.

B-Lymphocytes↗
PubMed2006

Prevalence, structure and expression of urease genes in Shiga toxin-producing Escherichia coli from humans and the environment.

A component of the ure gene cluster in E. coli, ureC, encodes a subunit of urease. We have investigated the distribution of ureC in 202 Shiga toxin-producing E. coli (STEC) strains from Austria belonging to 61 different serotypes. These strains were of human (n=150), animal (n=38), and food (n=14) origin. ureC was present in all 72 E. coli O157:H7 and O157:NM (non-motile) strains, as well as in all 29 strains of serotypes O26:H11/NM, O111:H8/NM and O145:NM. In contrast, none of eight sorbitol-fermenting E. coli O157:NM were ureC-positive. ureC occurred significantly more frequently among STEC that carry eae (113 of 132; 85.6%) than among eae-negative STEC strains (four of 70; 5.7%; p<0.0001). However, only 4 (2%) of the 202 strains (3.4% of ureC positive strains) expressed urease activity. There was no significant association (p=0.56) between urease expression and the source of the isolates (humans vs. animals). Nucleotide sequence analysis of PCR amplicons derived from all seven genes of the ure cluster in STEC of 10 different serotypes demonstrated a high degree of homology (>or=99%), indicating a recent acquisition of not necessarily expressed ure genes.

Adhesins, Bacterial↗
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↗
PubMed2006

Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia.

Five hundred and forty-five serum samples from donors from various parts of Mongolia were investigated for antibodies against the tick-borne encephalitis (TBE) virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. Seroprevalence against TBE was 5.1% in the province of Selenge and 0.9% in Bulgan province, seroprevalence against B. burgdorferi was 1.9% in Selenge province and Bulgan province, 13.9% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. Seroprevalence against A. phagocytophilum was 2.3% in Selenge province, 5.6% in Bulgan province, 2.8% in Dornogov province, and 3.0% in Tov province and Ulaanbaatar. We conclude that all three pathogens are endemic in Mongolia.

Anaplasma phagocytophilum↗
PubMed2006

Cytolethal distending toxins in Shiga toxin-producing Escherichia coli: alleles, serotype distribution and biological effects.

To assess the prevalence of cytolethal distending toxin (CDT) among Shiga toxin-producing Escherichia coli (STEC), 202 STEC strains were investigated using PCRs targeting various cdt alleles (cdt-I to cdt-V). Seven of the 202 strains contained cdt-III and an additional seven contained cdt-V. All 14 cdt-positive strains produced biologically active CDT, as demonstrated by a progressive distension of cultured Chinese hamster ovary cells. The CDT-positive STEC belonged to eight different serotypes, including sorbitol-fermenting O157 : NM (non-motile). The data demonstrate that CDT is present in some STEC serotypes only. However, more studies are required to evaluate whether CDT presence is associated with severe disease.

Alleles↗
PubMed2005

Diagnosis of bacteria in vitro by mass spectrometric fingerprinting:a pilot study.

The identification of bacteria by using conventional microbiological techniques can be very time-consuming and circumstantial. In contrast, the headspace screening of bacterial cultures by analyzing their emitted volatile compounds using mass spectrometry might provide a novel approach in diagnostic microbiology. In the present study different strains of Escherichia coli, Klebsiella, Citrobacter, Pseudomonas aeruginosa, Staphylococcus aureus, and Helicobacter pylori were investigated. The volatile compounds emitted by these bacteria in vitro were analyzed using proton-transfer-reaction mass spectrometry, which allows rapid and sensitive measurement. The detected patterns of volatile compounds produced by the investigated bacteria were compared and substantial differences regarding both quantity and quality were observed. In conclusion, the present study is the first to describe headspace screening of bacterial cultures as a potential diagnostic approach in medical microbiology.

Bacteria↗
PubMed2005

Antifungal activity of the local complement system in cerebral aspergillosis.

Dissemination of aspergillosis into the central nervous system is associated with nearly 100% mortality. To study the reasons for the antifungal immune failure we analyzed the efficacy of cerebral complement to combat the fungus Aspergillus. Incubation of Aspergillus in non-inflammatory cerebrospinal fluid (CSF) revealed that complement levels were sufficient to obtain a deposition on the surface, but opsonization was much weaker than in serum. Consequently complement deposition from normal CSF on fungal surface stimulated a very low phagocytic activity of microglia, granulocytes, monocytes and macrophages compared to stimulation by conidia opsonized in serum. Similarly, opsonization of Aspergillus by CSF was not sufficient to induce an oxidative burst in infiltrating granulocytes, whereas conidia opsonized in serum induced a clear respiratory signal. Thus, granulocytes were capable of considerably reducing the viability of serum-opsonized Aspergillus conidia, but not of conidia opsonized in CSF. The limited efficacy of antifungal attack by cerebral complement can be partly compensated by enhanced synthesis, leading to elevated complement concentrations in CSF derived from a patient with cerebral aspergillosis. This inflammatory CSF was able to induce (i) a higher complement deposition on the Aspergillus surface than non-inflammatory CSF, (ii) an accumulation of complement activation products and (iii) an increase in phagocytic and killing activity of infiltrating granulocytes. However, levels and efficacy of the serum-derived complement were not reached. These data indicate that low local complement synthesis and activation may represent a central reason for the insufficient antifungal defense in the brain and the high mortality rate of cerebral aspergillosis.

Antibodies, Fungal↗
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↗
PubMed2005

C-type lectin-independent interaction of complement opsonized HIV with monocyte-derived dendritic cells.

HIV directly activates the complement cascade and is, therefore, opsonized with C3-cleavage products in vivo. This cloud of C3 fragments on the viral surface may impair the interaction of the HIV envelope glycoproteins gp120/gp41 with C-type lectins expressed on immature dendritic cells (iDC). Therefore, we determined the accessibility of gp120 after opsonization and compared the interaction of DC with non-opsonized or complement-opsonized HIV. The recognition of native gp120 was drastically impaired when the virus was covered by complement. Independent of opsonization, similar amounts of HIV bound to DC. The interaction of iDC and the infection of DC-PBL co-cultures with non-opsonized virus was significantly reduced by mannan and antibodies which inhibit the ICAM-1-CR3 interaction. The binding of opsonized virus to iDC was reduced by an anti-CR3-antibody, which interferes with the binding of C3 fragments, but was not affected by mannan. Complement enhanced the HIV infection of DC and DC-PBL co-cultures significantly. Mannan did not inhibit the complement-dependent enhancement of infection. Thus, non-opsonized and opsonized HIV interacted with iDC, although the binding mechanisms seemed to differ. As HIV is opsonized in vivo, the C-type lectin-independent interaction of opsonized viruses with iDC has to be taken into account.

Antibodies, Monoclonal↗
PubMed2005

Antimicrobial susceptibilities of Austrian Francisella tularensis holarctica biovar II strains.

The antibiotic susceptibilities of 50 Francisella tularensis subsp. holarctica biovar II strains isolated from hares and human patients from the eastern part of Austria were examined. Minimum inhibitory concentrations (MICs) of 24 antimicrobial agents were determined using Eteststrade mark on cysteine heart agar plates supplemented with 10% sheep blood. All isolates were sensitive to tetracyclines, aminoglycosides, quinolones, chloramphenicol and rifampicin. Resistance was observed in all isolates against macrolides, penicillins and aztreonam. Bacteria were resistant to cephalosporins and carbapenems, except for 8% of strains investigated that were susceptible or intermediately susceptible. Our in vitro susceptibility data can be applied for the detection and comparison of resistance development and to provide in vitro data for the guidance of therapy.

Aminoglycosides↗
PubMed2005

HIV-infection of the central nervous system: the tightrope walk of innate immunity.

Infection of the central nervous system (CNS) by HIV is a frequent and sometimes very early event in the course of HIV pathogenesis. Possible consequences are diverse symptoms of neurological dysfunction, but also the establishment of a lifelong latent viral reservoir in the brain. Whereas in the periphery innate and adaptive immunity are equal partners, the blood-brain barrier (BBB) with its restricted access of peripheral immune effectors shifts this balance in favour of the local innate immunity. Four main elements of cerebral innate immunity are discussed in the present article, including two cell types with immunological functions and two soluble immune systems: (1) the stimulation of microglial cells as the predominant brain-resident immune cell and the main local reservoir for the virus; (2) the reaction of astrocytes in response to viral infection; (3) the activation of the local complement system as important soluble immune cascade; and (4) the role of chemokines and cytokines which help to conduct and cross-link the interplay between the different immune elements. These components of the cerebral innate immunity do not act separately from each other but form a functional immunity network. A dual role of these components with both harmful and protective effects further enhances the complexity of the mutual interactions.

Astrocytes↗
PubMed2005

Mechanisms promoting dendritic cell-mediated transmission of HIV.

Dendritic cells (DC) survey epithelial or mucosal surfaces for antigens, take them up via their endocytic or phagocytic receptors, process the captured antigens and migrate to the lymphatic tissues. In the draining lymph nodes they present the immunogenic peptides to T cells thereby inducing antigen-specific immune responses. HIV-1 in turn seems to have developed mechanisms to exploit the natural trafficking of DC to establish infection in its primary targets, the CD4+ T cells. This review discusses several aspects of DC-HIV interactions with a main focus on the attachment, internalisation and transmission of the virus by DC to cells, susceptible for infection with HIV.

Dendritic Cells↗