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Biomedical subjects

M Herrmann

Publications and source records attributed to M Herrmann.

At least 19 recordsLinked to original sources
PubMed2002

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Antifungal Agents↗
PubMed2002

Apoptosis of the teratocarcinoma cell line Tera-1 leads to the cleavage of HERV-K10gag proteins by caspases and/or granzyme B.

Redistribution, post-translational modifications and coclustering with viral antigens contribute to the immunogenicity of apoptotic cell-derived autoantigens. Almost all known targets of the humoral autoimmune response in systemic lupus erythematosus (SLE) are cleaved by caspases or granzyme B during apoptosis. Antibodies against retroviral proteins can frequently be detected in the sera of SLE patients without overt retroviral infections. These antibodies may represent cross-reactive antibodies or may have been induced by proteins encoded by endogenous retroviral sequences. We used Tera-1 cells that abundantly express a group-specific antigen of human endogenous retroviruses, HERV-K10gag polyprotein, to investigate its processing during apoptosis. Tera-1 cells induced to undergo apoptosis showed an altered HERV-K10gag processing compared with viable cells. In addition, granzyme B was able to cleave HERV-K10gag isolated from viable Tera-1 cells. Similar to nuclear autoantigens, endogenous retroviral proteins are cleaved during the execution phase of apoptosis. These post-translational modifications may result in the generation of T-cell neoepitopes or a changed epitope hierarchy of retroviral proteins. Therefore, immunogenicity of retroviral antigens in SLE patients may result from a similar mechanism as described for nuclear autoantigens.

Amino Acid Sequence↗
PubMed2002

Anti-inflammatory effect of low-dose X-irradiation and the involvement of a TGF-beta1-induced down-regulation of leukocyte/endothelial cell adhesion.

PURPOSE: Low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect, but the underlying radiobiological and immunological mechanisms remain elusive. In recent studies, we observed a reduced adhesion of peripheral blood mononuclear cells (PBMC) to endothelial cells (EC) after LD-RT (0.3-0.7 Gy). This shows that this treatment affects the initial steps of the inflammatory response. To explore the role of inflammatory mediators in this process, we investigated the expression of Transforming growth factor beta(1) (TGF-beta(1)) and Interleukin 6 (IL-6) after LD-RT. MATERIALS AND METHODS: EC were grown to subconfluence and irradiated with single-dose LD-RT. Twenty-hours after irradiation, EC were treated with IL-1beta for 4 h and then incubated with peripheral blood mononuclear cells (PBMC). Adherent PBMC were counted when using light microscopy. Expression of the cytokines TGF-beta(1) and IL-6 was measured by ELISA, and mRNA levels were analysed by the RNAse-protection assay (RPA). Surface expression of E-selectin was quantified by flow cytometry. RESULTS: A relative minimum of adhesion was observed after LD-RT between 0.3 and 0.7 Gy. This was paralleled by an expression maximum of TGF-beta(1) and IL-6, as shown by protein and mRNA levels, respectively. Neutralization of TGF-beta(1) by monoclonal antibodies, but not of IL-6, increased PBMC adhesion to EC nearly to control levels. In addition, fluorescence activated cell sorter (FACS) analysis of irradiated EC demonstrated a down-regulation of E-selectin in the same dose range. CONCLUSION: Low-dose X-irradiation between 0.3 and 0.7 Gy induced a relative maximum of TGF-beta(1) production by stimulated EC. This results in a down-regulation of leukocyte/PBMC adhesion and may contribute to the anti-inflammatory effect of LD-RT.

Animals↗
PubMed2002

Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection.

Cytokines (IL-1, IL-6, IL-8, IL-11, TNF, IFN-gamma, and TGF-beta) and growth factors (EGF, bFGF, aFGF, and KGF) play an important role in modulation of hormone secretion by directly influencing specific enzyme steps of steroidogenesis in various endocrine cell types. For this tabular data collection, the following enzyme steps were considered: steroidogenic acute regulatory protein (StAR), side chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase/17,20-lyase (P450c17), 17-beta-hydroxysteroid-dehydrogenase, aromatase complex, 5-alpha-reductase, P450c21, DHEAS sulfatase, and DHEA sulfotransferase. This collection summarizes the current information on how the mentioned cytokines and growth factors influence particular enzyme steps.

17-Hydroxysteroid Dehydrogenases↗
PubMed2001

5,6-carboxyfluorescein diacetate succinimidyl ester-labeled apoptotic and necrotic as well as detergent-treated cells can be traced in composite cell samples.

Detection of dividing cells by staining with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) has been widely used in flow-cytometric protocols. We analyzed the fate of CFSE in cells undergoing apoptotic or necrotic cell death, respectively. Peripheral blood mononuclear cells (PBMC) were stained with CFSE. Apoptosis was induced by UVB irradiation and necrosis by incubation at 56 degrees C for 30 min. In some experiments, labeled cells were permeabilized with detergent and CFSE association with nuclei was assessed. We observed that (i) CFSE remains stably detectable in apoptotic and necrotic cells; (ii) CFSE remains stably associated with the nuclei of cells even after their lysis by detergent; (iii) CFSE labeling does not interfere with the induction of cell death; and (iv) CFSE is not transferred from stained dying cells to unstained neighboring counterparts. We conclude that, in addition to tracking viable cells, CFSE can be used to trace dying cells in composite samples. We demonstrated that CFSE labeling does not influence the induction and the execution of apoptosis or necrosis.

Apoptosis↗
PubMed2001

Control of semantic interference in episodic memory retrieval is associated with an anterior cingulate-prefrontal activation pattern.

Prefrontal activation is a consistent finding in functional neuroimaging studies of episodic memory retrieval. In the present study we aimed at a further analysis of prefrontal neural systems involved in the executive control of context-specific properties in episodic memory retrieval using an event-related fMRI design. Nine subjects were asked to learn two 20-item word lists that consisted of concrete nouns assigned to four semantic categories. Ten items of both word lists referred to the same semantic category. Subjects were instructed to determine whether nouns displayed in random order corresponded to the first 20-item target list. The interference evoked by the retrieval of semantically related items of the second list resulted in significantly longer reaction times compared to the noninterference condition. Contrasting the interference against the noninterference retrieval condition demonstrated an activation pattern that comprised a right anterior cingulate and frontal opercular area and a left-lateralized dorsolateral prefrontal region. Trial averaged time series revealed that the PFC areas were selectively activated at the interference condition and did not respond to the familiarity of learned words. These findings suggest a functionally separable role of prefrontal cortical areas mediating processes associated with the executive control of interfering context information in episodic memory retrieval.

Adult↗
PubMed2001

Teichoic acid enhances adhesion of Staphylococcus epidermidis to immobilized fibronectin.

Adhesion is a prerequisite for coagulase-negative staphylococci to cause invasive disease and may be mediated by adhesive host molecules adsorbed on implanted polymers. In this study, we can confirm previous observations demonstrating binding of Staphylococcus epidermidis to fibronectin (FN) adsorbed polymer surfaces. So far, the nature of FN-recognizing adhesin(s) in S. epidermidis remains elusive. Since teichoic acids (TA) have been shown to exert binding functions for extracellular matrix molecules in several Gram-positive species, we have purified wall TA of S. epidermidis laboratory strains KH11 and RP62A, as well as clinical isolate AB9. Using a polymethylmethacrylate (PMMA) coverslip adhesion assay, a microtitre plate assay and a particle agglutination assay, we found that purified TA significantly enhanced adhesion of S. epidermidis KH11 and RP62A to FN coated surfaces. Enhanced adhesion was dose-dependent and saturable. Preincubation, either of microorganisms or of FN coated surfaces, with TA promoted adhesion, while adhesion to TA-adsorbed PMMA was comparably low. This observation may suggest a potential role of cell wall carbohydrates as bridging molecules between microorganisms and immobilized FN in early steps of S. epidermidis pathogenesis.

Bacterial Adhesion↗
PubMed2001

Apoptotic UV-irradiated lymphocytes undergo protease mediated shedding of L-selectin in vitro.

Adhesion between circulating lymphocytes and endothelial cells of the vessel wall depends on the expression of selectins and is the first step of tissue invasion which characterises inflammation. UV-B is well known to induce apoptosis in lymphocytes. We show that induction of apoptosis by any procedure leads to a metalloprotease mediated shedding of L-selectin from the surface of T-lymphocytes. Together with the previously published immunosuppressive action of apoptotic cells, this may contribute to the clinical effect of UV-B application, especially in photopheresis.

Apoptosis↗
PubMed2001

Suppression of type 2 NO-synthase activity in macrophages by Candida albicans.

Macrophages (Mphi) are important for the defence against experimental disseminated candidiasis. Nitric oxide (NO) generated by the inducible isoform of NO-synthase (iNOS or NOS2) is thought to contribute to candidacidal effector functions by activated Mphi. In vitro, however, Mphi cannot control the growth and hyphal formation of Candida (C.) albicans. Using mouse peritoneal exudate Mphi stimulated with IFN-gamma and LPS, we examined the effect of C. albicans on NO synthesis, NOS2 enzyme activity and macrophage survival. C. albicans effectively inhibited the production of NO via suppression of total NOS2 protein and enzyme activity. Hyphal formation of C. albicans and direct interaction with host cells was required for maximum inhibition of NO production, whereas non-filamentous C. albicans mutants released soluble products that effected only partial inhibition. Ultimately, Mphi underwent apoptotic cell death after infection with C. albicans wild-type strains capable of hyphal formation, indicated by loss of the mitochondrial membrane potential and onset of chromatin degradation. NO suppression and Mphi killing are potent activities of C. albicans that may augment virulence of C. albicans.

Animals↗
PubMed2001

Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death.

The phagocytosis of dying cells is an integral feature of apoptosis and necrosis. There are many receptors involved in recognition of dying cells, however, the molecular mechanisms of the scavenging process remain elusive. The activation by necrotic cells of complement is well established, however, the importance of complement in the scavenging process of apoptotic cells was just recently described. Here we report that the complement components C3 and C4 immediately bound to necrotic cells. The binding of complement was much higher for lymphocytes compared to granulocytes. In case of apoptotic cell death complement binding was a rather late event, which in lymphocytes was preceded by secondary necrosis. Taken together complement binding is an immediate early feature of necrosis and a rather late event during apoptotic cell death. We conclude that complement may serve as an opsonin for fragments of apoptotic cells that have escaped regular scavenging mechanisms.

Apoptosis↗
PubMed2001

Early neurobehavioral disorders after cardiac surgery: a comparative analysis of coronary artery bypass graft surgery and valve replacement.

OBJECTIVE: To analyze neurobehavioral disorders in the early postoperative period after valve replacement and coronary artery bypass graft (CABG) surgery. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary bypass; 42 patients in the valve replacement surgery group and 42 patients in the CABG surgery group, with both groups matched post hoc for age, sex, and preoperative cognitive status. MEASUREMENTS AND MAIN RESULTS: All subjects were investigated preoperatively as well as 2 and 7 days postoperatively with a comprehensive neuropsychologic and neuropsychiatric assessment. The groups did not significantly differ with respect to the incidence of postoperative neuropsychiatric disorders. Valve replacement surgery patients exhibited more severe neuropsychologic deficits and showed a slower recovery than patients who underwent CABG surgery. In both groups, postoperative neuropsychologic alterations were most marked in fluency, arithmetic, and memory performance. CONCLUSION: These results indicate that patients after valve replacement surgery have a higher risk of postoperative neuropsychologic alterations mainly attributable to temporal lobe dysfunction. This finding corresponds to a specific vulnerability of hippocampal structures to transient hypoxia.

Adult↗
PubMed2001

Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis.

Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation follows limits of number and diameter of tumor nodules. It has not been investigated whether there is a correlation of these parameters with vascular invasion. From 1989 to 2000, 1,188 liver transplantations were performed in 1,087 patients, including 120 patients (11%) with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm if the tumor appeared to be uninodular or of up to 3 cm in the case of 2 or 3 nodules. The postoperative mortality rate was 1.7%. One-, 5-, and 10-year survival was 90%, 71%, and 60%, respectively. In 940 transplantation patients without an HCC, these rates were 93%, 87%, and 83% (P < .0001). Vascular invasion and histopathologic grading were identified as prognostic parameters by multivariate analysis. In a logistic regression analysis, histopathologic grading and maximal diameter showed a significant correlation with a vascular invasion. Analyzing tumors larger than 5 cm, i.e., tumors not fulfilling the selection criteria as a result of diagnostic inaccuracy or progression thereafter, the rates of vascular invasion were significantly (P < .01) lower in patients suffering from well-differentiated tumors (25%) when compared with moderately and poorly differentiated tumors (100%). Liver transplantation is a safe and effective long-term treatment for small HCC in cirrhosis. Tumor diameter and number of nodules in correlation with the histopathologic grading were predictive of a vascular invasion only in HCC larger than 5 cm.

Adult↗
PubMed2001

Angioplasty increases target site concentrations of ciprofloxacin in patients with peripheral arterial occlusive disease.

OBJECTIVE: Patients with peripheral arterial occlusive disease are prone to soft tissue infections and frequently require antibiotics. To date, however, it is not known whether improvement of arterial blood flow by angioplasty of stenosis increases antibiotic concentrations in ischemic lesions. PATIENTS AND METHODS: All patients were scheduled to undergo elective percutaneous transluminal angioplasty (n = 10). Following a single, 400-mg dose of ciprofloxacin, drug concentrations in plasma, ischemic and healthy soft tissue; arterial peak systolic velocity; and ankle-brachial pressure index were assessed before and after angioplasty. Unbound ciprofloxacin concentrations were measured at the site of infection with use of in vivo microdialysis. RESULTS: Angioplasty increased peak systolic velocity and ankle-brachial pressure index compared with baseline (P <.002). Before angioplasty area under concentration-time curve (AUC(0-300)) values for ciprofloxacin were lower in ischemic tissue than in healthy tissue, with median values of 7.1 mg.h/L (range, 3.5-13.0) and 11.3 mg.h/L (range, 3.4-19.0), respectively (P =.03). After angioplasty AUC(0-300) values were identical in ischemic and healthy adipose tissue; median AUC(0-300) values were 8.0 mg.h/L (range, 4.0-20.7) and 8.5 mg.h/L (range, 4.4-22.9), respectively (P =.7). A combined in vivo pharmacokinetic/in vitro pharmacodynamic simulation based on tissue concentration data indicates that this difference in pharmacokinetics is also reflected in antimicrobial effect. CONCLUSION: Antibiotic concentrations are reduced significantly in ischemic lesions compared to those of healthy adipose tissue in patients with peripheral arterial occlusive disease. From the present data it might be speculated that improvement of arterial blood flow at the affected extremity is associated with increased cure rates of soft tissue infections in these patients.

Adipose Tissue↗
PubMed2001

The pathogenesis of autoimmune diseases.

Autoimmunopathies are chronic inflammatory diseases which can be subdivided into several specificities on the ground of the clinical picture as well as serological findings and involvement of organ systems like the kidney, central nervous system or the hematopoietic system. The pathogenesis of these diseases is incompletely understood. With the exception of rare diseases in which the autoantigens are known, in the most frequent autoimmunopathies like rheumatoid arthritis or Systemic Lupus Erythematosus (SLE) only some partial aspects of the pathogenetic scenario are understood and rather well substantiated by experimental data. In RA, there are controversies concerning the central involvement of T-lymphocytes and/or synovial fibroblasts in the initiation of the diseases. It is meanwhile well known that TNF-alpha and possibly other related cytokines are involved at least in the perpetuation of the inflammatory cascades. Specific blockade of TNF-alpha leads to rapid improvement of RA disease activity and can prevent tissue destruction. An intriguing hypothesis postulates a central role for a dysregulated apoptosis in the development of SLE. In this review we will concentrate on pathogenetic concepts of autoimmune diseases as exemplified by RA and SLE.

Animals↗
PubMed2001

Detection of differential gene expression in biofilm-forming versus planktonic populations of Staphylococcus aureus using micro-representational-difference analysis.

Microbial proliferation and biofilm formation on biologic or inert substrates are characteristics of invasive Staphylococcus aureus infections and is associated with phenotypic alterations such as reduced antimicrobial susceptibility. To identify genes which are typically expressed in biofilms, a micro-representational-difference analysis (micro-RDA) was adapted for gram-positive bacteria and used with cDNA derived from populations of S. aureus DSM 20231 growing in a biofilm or plankonically. In comparison to previously described cDNA RDA protocols, micro-RDA has the advantages that only minimal quantities of total RNA are needed and, most importantly, that total RNA can be used since the large amount of rRNA in total RNA does not interfere with the micro-RDA procedure. Using a series of spiked controls with various amounts of MS2 RNA in a background of total RNA from S. aureus, the equivalent of five copies of MS2 per cell were detectable after three rounds of subtractive enrichment. Five genes were identified as being differentially expressed in biofilm versus planktonic cultures. These genes revealed homology to a threonyl-tRNA synthetase, a phosphoglycerate mutase, a triosephosphate isomerase, an alcohol dehydrogenase I, and a ClpC ATPase. Differential levels of expression were subsequently confirmed by standard Northern blotting. In conclusion, micro-RDA is a sensitive and specific method to detect transcripts differentially expressed as a function of different S. aureus growth conditions.

Bacterial Proteins↗