Biomedical subjects

Holger Hennig

Publications and source records attributed to Holger Hennig.

10 recordsLinked to original sources

PubMed2006

Beta-(1-->3)-D-glucan modulates DNA binding of nuclear factors kappaB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1beta/IL-1 receptor antagonist ratio.

BACKGROUND: Beta-1-->3-D-glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. Employing a comprehensive methodological approach, the aim of our in vitro study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal beta-1-->3-D-glucan, i.e. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1). RESULTS: Despite an activation of nuclear factor (NF) kappaB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1beta, IL-6, tumor necrosis factor alpha or interferon gamma induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg/ml), likely due to binding of NFkappaB to a consensus site in the IL-8 promoter. An increase in IL-1receptor antagonist (RA) production (peak at 24 h: 12000 pg/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NFkappaB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-1beta and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1beta/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2. CONCLUSION: Thus, beta-1-->3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a beta-1-->3-D-glucan.

Bacterial Toxins↗

PubMed2005

Charge transfer driven by electron correlation: a non-Dyson propagator approach.

A hole charge created in a molecular system, for instance, by ionization, can migrate through the system solely driven by electron correlation. This charge transfer due to electron correlation is referred to as charge migration. We introduce in this work a new ab initio method analyzing charge migration due to electron correlation in molecules. This method, a third-order "non-Dyson" propagator approach, aims in the long run, in particular, at the calculation of charge migration in relatively large molecules such as oligopeptides. First results of the new non-Dyson method are compared with a previously used propagator approach.

Journal Article↗

PubMed2005

Electron correlation as the driving force for charge transfer: charge migration following ionization in N-methyl acetamide.

A hole charge created in a molecule, for instance, by ionization, can migrate through the system solely driven by electron correlation. The migration of a hole charge following ionization in N-methyl acetamide (a molecular system containing a peptide bond) is investigated. The initial hole charge is localized at one specific site of the molecule. Ab initio calculations show that nearly 90% of the hole migrates to a remote site of the molecule in 4.2 fs. This migration of charge is highly efficient and ultrafast. The underlying mechanism for this migration of a hole charge is identified and compared with a simple model.

Acetamides↗

PubMed2004

Interferon-alpha stimulation of liver cells enhances hepatitis delta virus RNA editing in early infection.

BACKGROUND/AIMS: RNA editing controls the formation of hepatitis-delta-antigen-S and -L and therefore plays a central role in the hepatitis-delta-virus (HDV) life-cycle. Editing is catalyzed by the enzyme Adenosine-deaminase-acting-on-RNA1 (ADAR1) of which two different forms, ADAR1-L and ADAR1-S, exist. As ADAR1-L is induced by interferon (IFN)-alpha, we examined the influence of IFN-alpha-stimulation of host cells on HDV-RNA editing. METHODS: Editing was studied in Huh-7-cells transfected with HDV-RNA on days 7, 14, 21 and 28 after transfection. ADAR1-L mRNA was measured by RT-PCR. RESULTS: IFN-alpha-treatment led to a 5-fold higher expression of ADAR1-L and to an increase in editing from 14+/-2% (SD) in unstimulated controls to 27+/-4% (SD) on day 7 after transfection. Editing further increases over time to the same maximum level of 35% in IFN-alpha-treated as well as untreated cells. CONCLUSIONS: By IFN-alpha-stimulation both ADAR1-L expression and editing are increased in Huh-7-cells at day 7, and the maximum level of edited antigenomes is reached earlier with IFN-alpha-treatment as compared to untreated cells. Thus, ADAR1-L appears to be able to increase editing, but the HDV genome apparently has an intrinsic negative feed-back regulation mechanism that limits editing to roughly a third of the genomes.

Adenosine Deaminase↗

PubMed2003

Molecular parameters for precise diagnosis of asymptomatic Epstein-Barr virus reactivation in healthy carriers.

Asymptomatic Epstein-Barr virus (EBV) reactivations periodically occur in oral mucosa-associated lymphoid tissues. Until now, EBV reactivation has been diagnosed by serologic profiles that suggest virus replication. Serologic responses, however, are delayed and do not necessarily indicate ongoing replicative activity. The aim of the present study was to establish in healthy carriers parameters for a molecular diagnosis of reactivated EBV infection. Recent studies emphasized the association of an increase in peripheral-B-cell viral load with replicative activity at remote sites. Therefore, real-time PCR was used to quantitate EBV genomes in the peripheral blood mononuclear cells (PBMC) (viral load) and plasma samples (viremia) of 22 healthy EBV-seropositive blood donors over a period of 15 months. Furthermore, transcription of the immediate-early gene encoding BZLF1 was investigated in the PBMC of all volunteers. Serology suggested reactivation in nine donors, of whom all but one showed at least once a significant increase in viral load. Another five individuals also exhibited significant changes in viral load but no serologic response. Of the 13 volunteers with significant increases in viral load, 6 had a period of viremia accompanying the rise in viral load. A stable viral load without viremia and negative serology was seen in eight adults. BZLF1 mRNA was undetectable throughout. We conclude that for healthy subjects serology underestimates the frequency of asymptomatic EBV reactivations. Prospective examination of peripheral viral load and viremia is suitable for the exact diagnosis of EBV reactivation, which might be of advantage for immunocompromised patients in whom EBV reactivations are considerably harmful.

Antibodies, Viral↗

PubMed2003

Detection of Marek's disease virus DNA in chicken but not in human plasma.

Marek's disease virus (MDV) causes a common lymphomatous and neuropathic disease in domestic chickens and, less commonly, turkeys and quail. It is a member of the alpha-herpesviruses and until now was considered to be strongly cell associated. In 1991, MDV was suggested to be the causative infectious agent of multiple sclerosis (MS) in humans. In a previous study, we investigated the leukocytes of 107 well-defined MS patients for the presence of MDV DNA but were unable to confirm a role for MDV in the pathogenesis of MS. A recent report (S. Laurent, E. Esnault, G. Dambrine, A. Goudeau, D. Choudat, and D. Rasschaert, J. Gen. Virol. 82:233-240, 2001) described the detection of MDV DNA in 20% of 202 human serum samples, regardless of whether the individuals were exposed to poultry. The detection of MDV DNA in chicken serum samples was reported as well. The aim of the present study was to investigate whether we can confirm the presence of MDV DNA in chickens and humans if we use plasma as the source for nucleic acid isolation. Leukocytes and plasma specimens from 16 chickens experimentally infected with MDV serotype 1 and plasma specimens from 300 volunteer blood donors were tested for MDV DNA by two different TaqMan PCR assays. MDV DNA was repeatedly found in the leukocytes as well as in the plasma specimens of all 16 animals. All human samples analyzed, however, tested negative by both assays. Accordingly, Marek's disease in chickens can be diagnosed by detection of MDV DNA in plasma as well as in leukocytes. Once again, we found no evidence for the spread of MDV to humans.

Animals↗

PubMed2002

Immunity against diphtheria and tetanus in German blood donors.

After the recent diphtheria epidemics in Eastern Europe in the early 1990s, we re-evaluated the diphtheria and tetanus immunity of 321 German blood donors (192 men and 129 women). The mean antitoxin levels of all blood donors in this study, measured by commercial ELISA, revealed a questionable protection (0.1-1.0 IU/ml) against diphtheria. In 1994, 66.4% were without immunity against diphtheria (55.0% in 1997/98), 32.1% (41.5% in 1997/98) showed questionable protection and only 1.5% (3.5% in 1997/98) had protective antitoxin levels. The evaluation of tetanus immunity revealed only 0.5% (1.1% in 1997/98) of the subjects with no protection and 9.1% (8.5% in 1997/98) with questionable protection. For this reason, we conclude that the diphtheria epidemics only lead to an insufficient improvement of the immunization status in a healthy German population.

Adolescent↗

PubMed2002

Frequency and load of hepatitis B virus DNA in first-time blood donors with antibodies to hepatitis B core antigen.

The objective of this study was to determine the frequency and load of hepatitis B virus (HBV) DNA in anti-HBc-positive first-time blood donors; it was designed to contribute to determining whether anti-HBc screening of blood donations might reduce the residual risk of posttransfusion HBV infection. A total of 14 251 first-time blood donors were tested for anti-HBc using a microparticle enzyme immunoassay; positive results were confirmed by a second enzyme-linked immunosorbent assay (ELISA). For the detection of HBV DNA from plasma samples, we developed a novel and highly sensitive real-time polymerase chain reaction (PCR) assay. The 95% detection limit of the method amounted to 27.8 IU/mL, consistent with the World Health Organization (WHO) international standard for HBV DNA. A total of 216 blood donors (1.52%) tested anti-HBc-positive in both tests, and 205 of them (16 HBsAg(+), 189 HBsAg(-)) were tested for HBV DNA. In 14 (87.5%) of the HBsAg-positive blood donors, HBV DNA was repeatedly detected, and in 3 (1.59%) of the HBsAg-negative donors, HBV DNA was also found repeatedly. In the 3 HBV DNA-positive, HBsAg-negative cases, anti-HBe and anti-HBs (> 100 IU/L) were also detectable. HBV DNA in HBsAg-negative as well as HBsAg-positive samples was seen at a low level. Thus, HBV DNA is sometimes found in HBsAg-negative, anti-HBc-positive, and anti-HBs-positive donors. Retrospective studies on regular blood donors and recipients are necessary to determine the infection rate due to those donations. Routine anti-HBc screening of blood donations could probably prevent some transfusion-transmitted HBV infections.

Base Sequence↗

PubMed2002

Inhibition of macrophage inflammatory protein-1 alpha production by Epstein-Barr virus.

Infection with Epstein-Barr virus (EBV) exerts substantially immunomodulating activities in vitro and in vivo. In this context, EBV-induced chemokine production and the influence of EBV on this highly redundant system of inflammatory proteins have hardly been investigated. This study analyzed the production of interleukin-8, RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on EBV infection of peripheral blood mononuclear cells from immune EBV-seropositive (EBV(+)) and noninfected EBV-seronegative (EBV(-)) individuals. EBV failed to induce the production of MIP-1 alpha in EBV(+) as well as EBV(-) individuals, whereas the other chemokines studied were readily expressed. Moreover, EBV completely down-regulated lipopolysaccharide (LPS)- and phytohemagglutinin-induced MIP-1 alpha production up to 4 hours after induction. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of EBV- and LPS-stimulated cultures revealed that EBV inhibited MIP-1 alpha production on the transcriptional level. This effect was abolished by addition of antiglycoprotein (gp)350/220, a monoclonal antibody against EBV's major envelope glycoprotein, which mediates binding of the virus to the EBV receptor, CD21. However, recombinant gp350/220 protein alone did not inhibit the LPS-induced MIP-1 alpha production, indicating that infection of the target cell is indispensable for this effect. In summary, we demonstrate a new immunomodulating activity of EBV on the chemokine system that probably helps the virus to evade the host's immune system favoring lifelong infection.

Antibodies, Viral↗

PubMed2002

Prestorage WBC filtration of RBC units with soft-shell filters: filtration performance and impact on RBCs during storage for 42 days.

BACKGROUND: The introduction of universal WBC filtration of RBCs prior to storage is currently under consideration in many countries, as it is thought to minimize the incidence of transfusion-associated adverse effects. Centrifugation of blood containers with newly developed soft-shell WBC filters is more convenient, and so of great interest. STUDY DESIGN AND METHODS: Two different quadruple blood pack systems with integrated soft-shell WBC filters were compared (Sepacell OptiPure RC, Baxter Biotech, vs. LCR 5, Maco Pharma). Buffy coat-depleted RBC units were investigated from whole-blood donations that were held for 2 to 3 hours before centrifugation and subsequent filtration at 22 degrees C (Group 1, OptiPure RC, 450 mL; Group 2, LCR 5, 450 mL; Group 3, OptiPure RC, 500 mL; Group 4, LCR 5, 500, mL, n = 12 per group). Filtration performance was analyzed, and the impact of WBC filtration on hemolysis rate, Hb content, pH, supernatant potassium, ATP, and 2,3 DPG was investigated weekly during storage for 42 days. RESULTS: Filtration reduced the WBC count by 4.4 to 5.1 log. Mean +/- SD Hb content was 44.7 +/- 3.0, 41.2 +/- 3.3, 53.1 +/- 5.0, and 51.5 +/- 6.3 g per unit, respectively, with a corresponding mean RBC recovery after filtration of 71.0 +/- 3.0, 68.3 +/- 3.3, 76.6 +/- 1.7, and 68.9 +/- 4.5 percent. WBC filtration resulted in a significant reduction of Hct (0.10-0.14) in all four groups. Investigation of all RBC storage variables revealed acceptable values throughout the storage for 42 days. CONCLUSION: WBC filtration with two newly developed soft-shell filters showed acceptable WBC-reduction efficacy without any difference between filter types in buffy coat-depleted RBCs from 450- and 500-mL whole-blood donations. However, the application of both filters resulted in an unacceptably low RBC recovery after filtration, which was particularly evident with the LCR5 filter. Our findings raise concern that WBC reduction with these filters may result in the production of RBCs with an inappropriately low Hb concentration.

2,3-Diphosphoglycerate↗