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Biomedical subjects

A Bierhaus

Publications and source records attributed to A Bierhaus.

62 records · Page 4Linked to original sources
PubMed1995

Antiparasitic treatment of patients with P. falciparum malaria reduces the ability of patient serum to induce tissue factor by decreasing NF-kappa B activation.

Serum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF-kappa B/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-kappa B activation was evident. Activation of NF-kappa B-like proteins was in part dependent on TNF alpha in patient serum, since a TNF alpha neutralizing antibody reduced induction of TF transcription and translation and induction of NF-kappa B-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-kappa B activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-kappa B-like binding site in the TF promotor. A mutant with deleted NF-kappa B, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-kappa B/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-kappa B-like proteins in post-treatment patient serum.

Antimalarials↗
PubMed1995

Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease.

The cellular interactions of advanced glycation end products (AGEs), which have been hypothesized to contribute to the development of vascular lesions, occur, at least in part, through their binding to a novel integral membrane protein, the receptor for AGEs (RAGE). Studies of human vascular segments show that endothelial RAGE expression at the antigen and mRNA level was variable and usually at low levels in samples from healthy individuals. In contrast, patients with a range of peripheral occlusive vascular diseases, with or without underlying diabetes, demonstrated prominent enhancement of endothelial RAGE expression. Smooth muscle cells and nerves in the vessel wall showed constitutively high levels of RAGE expression that were unchanged with aging (from 1 to 92 years) or by the presence of vascular disease. These data suggest that RAGE is likely to have ligands other than AGEs, and that multiple factors in addition to AGEs impact on its expression. Taken together, our findings suggest that RAGE may contribute to the pathogenesis of a range of vascular disorders.

Adult↗
PubMed1995

Tissue factor expression in an animal model of hydronephrosis.

BACKGROUND: Hydronephrosis is associated with interstitial fibrosis and occlusion of renal capillaries by fibrin. However, the mechanisms leading to fibrin formation is unknown. METHODS AND RESULTS: Twenty days after unilateral ligation of the ureter, interstitial fibrosis occurred in the ligated kidney. Fibrosis was preceded by infiltration of inflammatory cells (macrophages, B and T lymphocytes). Staining with an antibody against von Willebrand factor demonstrated newly formed capillaries in the fibrosing tissue as well as prominent fibrin deposition. Fibrin staining was found around vessels, in the interstitium, the glomeruli, and tubuli. Fibrin deposition was less prominent in the non-ligated kidney and almost absent in sham-operated animals. The expression of tissue factor, the central initiator of coagulation, was induced within 5 days after ligation in the operated kidney but not in the sham-operated animals. Tissue factor positivity was observed by immunohistochemistry in vascular endothelial cells, the vessel wall, tubular epithelial cells, glomerular capsular cells, Bowman's space and in the interstitium. Tissue factor induction was due to increased transcription, since in-situ hybridization showed increased levels of mRNA in the ligated kidney compared to sham-operated rats. The tissue factor gene is under control of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). When extracts of operated organs were compared with kidneys of sham-operated rats or contralateral kidneys in electrophoretic mobility shift assays, an increase in AP-1 and NF-kappa B binding activity to their respective binding sites in the tissue factor gene was observed in the operated, but not in the contralateral kidney or kidneys of sham-operated animals. CONCLUSION: Ureteral ligation leads to infiltration of inflammatory cells, increased AP-1 and NF-kappa B expression in the kidney, resulting in increased tissue factor transcription and translation, and ultimately in increased fibrin deposition.

Animals↗
PubMed1994

Elevated thrombomodulin plasma levels as a result of endothelial involvement in plasmodium falciparum malaria.

We used thrombomodulin (TM) to assess the participation of the vascular endothelium in human Plasmodium falciparum (P.F.) malaria. Before therapy TM plasma levels were elevated in P.F. malaria and fell to normal values during therapy. Parasitemia, TNF alpha, elastase and TAT levels correlated directly with TM. Elevated TM levels can not be explained by increased synthesis, since incubating HUVEC with pretherapy serum of patients with P.F. malaria, but not reconvalescence serum, suppressed TM transcription. This was partially prevented by adding a TNF alpha neutralizing antibody to patient serum before incubation with HUVEC. However, TNF alpha does not release TM from cultured HUVEC in vitro. Coincubation of HUVEC with pretherapy serum together with neutrophils resulted in endothelial cell destruction, which could be partly prevented by a TNF alpha neutralizing antibody. Hence the increase of TM during P.F. malaria might reflect the concerted action of cytokines and neutrophils on HUVEC.

Antimalarials↗
PubMed1992

[Separation of urologic tumors cells from Cell Saver blood using a membrane filter. A new method in autotransfusion?].

Tumor cells of three urological longterm cell lines have been labelled with 35[S]-Methionin and added to red cell concentrates. Red cell concentrates rich in tumor cells were passed through a cell saver and two special membranfilters under standard conditions. The 35[S]-Methionin labelled tumor cells were detected by liquid scintillation counting. On an average, only 0.027% of the radioactivity was left after passing through the cell saver and the membran filters in the 12 experiments. If investigations in clinical use of cell-saver and membran filter confirm these results, there will be significant consequences in urological tumor surgery by the possibility of transfusing the salvaged autologous blood.

Blood Component Removal↗
PubMed1991

Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels.

PURPOSE: Hemostatic alterations and elevated tumor necrosis factor/cachectin (TNF alpha) serum levels may contribute to the pathogenesis of organ complications in human Plasmodium falciparum malaria. Therefore, we examined whether altered protein C (PC) and thrombin-antithrombin III (TAT) plasma levels correlated with TNF alpha serum concentrations, parasitemia, and the clinical course of human P. falciparum malaria. PATIENTS AND METHODS: Forty-seven patients with P. falciparum malaria were evaluated prospectively before and during antiparasitic therapy. TNF alpha serum levels were determined by immunoradiometric assay, PC and TAT plasma antigen by enzyme-linked immunosorbent assay, and PC and PC inhibitor-1 (PCI-1) activity levels by functional tests. Cultured endothelial cells were incubated with serum from four patients with malaria and from healthy control subjects and then assayed for procoagulant activity. Northern blot hybridization was used to detect tissue factor mRNA. RESULTS: In vivo, TNF alpha serum concentrations were elevated (median: 38.6 pg/mL; n = 47) while plasma levels of PC (antigen 55.4%; activity 39.0%; n = 47) and PCI-1 (0.56 U/L) were decreased in almost all patients before antiparasitic treatment. At the same time, TAT concentrations were high. These alterations correlated significantly (p less than 0.01) both with the severity of the disease (as defined by organ impairment) and with the number of circulating parasitized erythrocytes. Low PCI-1 activity correlated with low PC activity (p less than 0.001) and antigen (p less than 0.05) levels. The plasma level of coagulation factor IX, another vitamin K-dependent protein, was not significantly changed. In vitro, incubation of endothelial cells with patient serum (severe P. falciparum malaria) increased both endothelial cell procoagulant activity and cytoplasmic tissue factor mRNA levels. CONCLUSION: Elevated levels of TNF alpha and TAT, decreased plasma levels of anticoagulant PC, and the induction of procoagulant activity in endothelial cells by patient serum indicate a shift in the balance of hemostatic activity towards a procoagulant state in P. falciparum malaria. The alterations in TNF alpha, TAT, and PC levels may be a response to infection, since they correlate with parasitemia and are reversed during antiparasitic treatment.

Animals↗