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S Russwurm

Publications and source records attributed to S Russwurm.

15 recordsLinked to original sources
PubMed2003

Microarray technology--the future analyses tool in exercise physiology?

Microarray analysis offers a set of analytical platforms that provide rapid, affordable and substantial information at the DNA, RNA or protein level. It enables the analysis of thousands of genes simultaneously in a parallel manner across samples derived from various biological sources and treatment regimens. This development became possible as a result of the combination of three technological advances achieved at the beginning of the 1990's, namely parallelism, miniaturization and automation. In regular physical checkups the microarray technology could be used to supplement the current spectrum of tests and therefore enhance the quality of the data obtained. Arrays for analyses of RNA expression will allow gene expression profiling also in exercise physiology. DNA chips may also be used for genetic screening and diagnostics to analyze polymorphisms and mutations which may underlie genetic diseases or interindividual variations between subjects. Using microarrays in exercise physiology will provide new insights into the complex molecular mechanisms of the exercise-induced stress response, adaptation to training and modulation of immune function. Gene expression profiling and genetic screening will probably help to characterize and predict the individually variable response to and efficiency of training.

Exercise↗
PubMed2001

Procalcitonin and CGRP-1 mrna expression in various human tissues.

Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.

Calcitonin↗
PubMed2000

Lipopolysaccharide induces distinct alterations in the microtubule cytoskeleton of monocytes.

Microtubules are obligate functional elements of almost all eukaryotic cells. They are involved in a broad range of essential cellular functions and structural changes of this system may trigger cell death. Recently, we have reported that lipopolysaccharides inhibit in vitro microtubule formation due to exclusion of microtubule-associated proteins. The distinct epitopes of lipopolysaccharides responsible for these effects and the in vivo relevance of these data are unknown. Therefore, this study was conducted to elucidate the effects of lipid A, the biologically active motif of lipopolysaccharides, on microtubule formation in vitro and to prove whether lipopolysaccharides affect the microtubule architecture of cultured human monocytes in vivo. Despite a dose- and pH-dependent inhibition of microtubule formation by lipopolysaccharides, inhibition of microtubule assembly could be mimicked by lipid A. Near-infrared two-photon microscopy revealed that human peripheral blood monocytes accumulate lipopolysaccharides. A vesicular distribution pattern of lipopolysaccharides within the monocytes was observed. Confocal laser scanning microscopy demonstrated alterations in the microtubule architecture of monocytes after incubation with lipopolysaccharides. Lipid A seems to be responsible for the observed crosstalk between lipopolysaccharides and microtubule proteins. Furthermore, our data indicate that lipopoly-saccharides may affect the microtubule architecture in human monocytes after intracellular accumulation directly. Therefore, we conclude, that the microtubule cytoskeleton is an essential intracellular target for sepsis-relevant bacterial components such as lipopolysaccharides.

Animals↗
PubMed2000

Modulation of the ceramide level, a novel therapeutic concept?

The sphingomyelin (SM) pathway is an ubiquitous and evolutionarily conserved signaling system in which ceramide (CA), generated from SM by the action of various isoforms of sphingomyelinases (SMases) functions as an important second messenger. Recent evidence suggests that branching pathways of sphingolipid metabolism mediate either apoptotic or mitogenic responses depending on cell type and the nature of the stimulus. Events involving SM metabolites and CA in particular include proliferation, differentiation and growth arrest as well as the induction of apoptosis. An improved understanding of SMase-dependent signaling may afford relevant insights into the pathogenesis of diseases and provide novel strategies and selective targets for a therapeutic intervention e.g. in cancer, cardiovascular and neurodegenerative diseases, HIV and septic shock. This article briefly summarizes the role of SMases in signaling pathways, its potential contribution in the development and maintenance of various pathobiological states and analyzes the perspective of a potentially isotype-specifc inhibition of SMases as a novel therapeutic concept.

Animals↗
PubMed1999

Microtubule formation and kinesin-driven microtubule gliding in vitro in the presence of lipopolysaccharide.

Lipopolysaccharide (LPS) is a main trigger substance for the development of septic shock and multiple organ failure. We showed by turbidity measurements that LPS inhibits microtubule formation in a pH-dependent manner. Inhibition was found to be not only due to sequestration of MAP2 by LPS, but also of MAP1 and tau MAPs, indicating that LPS is able to react with a broad variety of MAPs. LPS-induced inhibition of microtubule formation could be compensated by additional tau or by addition of taxol. Dot blots revealed that LPS binds directly to tau, but seems not to bind to tubulin. As tau is expressed in various tissue types involved in multiorgan failure, it might be regarded as a further target for LPS action. In contrast, kinesin-dependent microtubule gliding was not affected by LPS. The toxin neither blocked the cargo (vesicle) nor the microtubule binding site of kinesin, suggesting a certain specificity of LPS-MAP interaction.

Animals↗
PubMed1999

HepG2 human hepatoma cells express multiple cytokine genes.

Although cytokines are known to be involved in the regulation of a variety of hepatocellular functions, hepatocytes themselves are generally considered only targets but not producers of these important mediators. In order to investigate whether cells of hepatocellular linages are a potential source of various regulatory cytokines we have estimated the multiple cytokine gene expression in the culture of well differentiated human HepG2 hepatoma cells using RT-PCR. Our findings demonstrate that HepG2 cells express mRNAs for interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), macrophage colony-stimulating factor (M-CSF), oncostatin-M (OSM), intercellular adhesion molecule (ICAM-1), interleukin 4 (IL-4), IL-5, IL-7, IL-10, IL-11, IL-12 and IL-6 receptor (IL-6R). At the same time the expression of IL-1, IL-2, IL-3, IL-6, CD40 ligand and IL-2R genes was not detected. It was concluded that hepatocytes are potential producers of a variety of cytokines, some of them being able to regulate hepatocellular functions directly, while others are important regulators of leukocyte activity. Thus, on the one hand, hepatocytes may express autoregulatory cytokines and on the other hand, influence the functions of other liver cells like Kupffer, Ito or endothelial cells. Due to their large amount, liver parenchymal cells could be an important source of sytemically acting pro- and anti-inflammatory and other regulatory cytokines.

CD40 Antigens↗
PubMed1999

Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro.

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.

Base Sequence↗
PubMed1999

Outcome prediction by traditional and new markers of inflammation in patients with sepsis.

Patients (n=242) admitted to intensive care unit for longer than 48 hours were categorised for sepsis according to American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference criteria. Body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT) as well as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, IL-10 and HLA-DR expression on monocytes were determined. Data of one randomly chosen day per patient entered analysis. Immunologic mediators contributing significantly to outcome were determined by logistic regression analysis. Area under the curves (AUC) of receiver operating characteristic curves of clinical markers of inflammation predicting prognosis were compared with AUC of relevant immunologic mediators. TNF-alpha, IL-6 and HLA-DR expression on monocytes were significantly associated with outcome; the AUC's were 0.835, 0.844 and 0.761 respectively. AUC's for clinical markers were 0.878, 0.811, 0.620 and 0.614 for PCT, CRP, leukocyte count and body temperature respectively. PCT had the highest AUC compared to other clinical markers. These data indicate that PCT might be a better marker than the classic criteria of inflammation, CRP, leukocyte count, and body temperature to identify patients endangered by severe infection or sepsis.

Adult↗
PubMed1999

Molecular aspects and natural source of procalcitonin.

The search for sensitive and specific markers of systemic infection has shown that procalcitonin levels are increased in sepsis, and, consequently, this plasma protein has come into the focus of clinical research. Human procalcitonin is encoded by the Calc-l gene, which gives rise to two alternatively spliced transcripts. Despite systemic investigation of the Calc-l gene and mechanisms of the tissue-specific regulation and alternative splicing, little is known about the biology of procalcitonin and the cells which express this protein during inflammation. Here we focus on the molecular and biochemical properties of the molecule and summarize the known biological functions of procalcitonin. We report on the structure of the Calc-l gene, the amino acid conservation of procalcitonin in different species, and the consensus sequences of the protein with regard to sites relevant for posttranslational modification, spatial distribution, and homologies to other cytokines. We discuss aspects of intracellular location of procalcitonin and demonstrate that it has the characteristics of a secreted protein.

Alternative Splicing↗
PubMed1998

Lipopolysaccharide-caused fragmentation of individual microtubules in vitro observed by video-enhanced differential interference contrast microscopy.

Microtubule disassembly is commonly believed to be a process of endwise tubulin dimer release. The present study demonstrates by video interference contrast microscopy that Escherichia coli lipopolysaccharide (LPS) caused microtubule disassembly in vitro by both endwise shortening and fragmentation. In contrast, the microtubules were only shortened from their ends in the presence of DNA, used as another example of a macromolecular microtubule effector. LPS-caused microtubule fragmentation was confirmed by transmission electron microscopy. Because of its ability to induce both fragmentation and endwise shortening, LPS, which is involved in sepsis pathogenesis, has to be regarded as a highly active microtubule-destabilizing agent.

Animals↗
PubMed1997

Modified low density lipoprotein delivers substrate for ceramide formation and stimulates the sphingomyelin-ceramide pathway in human macrophages.

Exposure of human blood monocytes derived macrophages to modified (oxidized or acetylated) LDL induced a approximately 40% elevation (60 pmol/10(6) cells) of the endogenous level of the sphingolipid ceramide. A rise of both neutral and acidic SMase activity was found after treatment with oxidized LDL (250 and 80%), while addition of acLDL stimulated only the neutral enzyme (280%). Sphingo(phospho)lipids from LDL were transferred to the cell membrane and distributed into intracellular compartments as observed with acLDL containing BODIPY-FL-C5-SM. Quantitation of ceramide after the addition of [3H-N-acetyl]- or BODIPY-FL-C5-SM-labeled modified LDL (27 microg/ml) to the cell culture medium indicated that approximately 210 pmol CA/10(6) cells was generated from exogenous (ox/acLDL) SM. These results demonstrate a stimulation of the sphingomyelin-ceramide pathway by modified LDL utilizing primarily exogenous (LDL-derived) substrate and suggest that the effects of modified LDL are at least partially due to an increased level of the messenger ceramide.

Boron Compounds↗
PubMed1994

Generation of reactive oxygen species and activity of platelet-activating factor acetylhydrolase in human monocyte-derived macrophages.

Monocytes were prepared from healthy human volunteers and were allowed to differentiate into macrophages by adhesion to plastic surface and cultured over 7 days in presence of either 10% fetal calf serum (FCS), human control serum or serum from hyperlipaemic patients. Hyperlipaemic serum stimulated the differentiation (measured as an increase in cellular protein and DNA content) to a higher extent when compared to control serum and FCS. With all sera a marked increase of the cellular activity of the enzyme platelet-activating factor acetylhydrolase (PAF-AH) and a tremendous decrease in the capacity of cells to generate reactive oxygen species (ROS) was observed. After seven days of culture the increase in PAH-AH activity was about 19-fold with hyperlipaemic serum, 11-fold with control serum and 6-fold with FCS. During the same period of time ROS generation measured as zymosan-induced chemiluminescence decreased by about 98% and no significant differences between the three types of serum were found. The results indicate that the activity of PAF-AH and the capacity of ROS generation which are both assumed to play an important role in the oxidation of low-density lipoproteins (LDL) and thus in the development of atherosclerosis, change in opposite direction during the differentiation of blood monocytes into macrophages, and that hyperlipaemic serum stimulates PAF-AH activity but not ROS generation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMedDate not supplied

[Procalcitonin as monocytic marker for early diagnosis in septic abortion].

BACKGROUND: In search of sensitive and specific markers of systemic infection procalcitonin (PCT) recently was promoted to the focus of clinical research. Little is known about the biology of PCT and until now no data have been presented about clinical importance of PCT in obstetric patients. PATIENT AND METHODS: Daily PCT values in a 17 year old patient with septic abortion were compared with established markers of systemic inflammation. Cultivated monocytes were analyzed by the means of indirect immunofluorescence for intracellular distribution of PCT. Additionally, PCT release into culture medium was examined. RESULTS: PCT values in comparison with established inflammation markers was demonstrated in the patient with septic abortion. Indirect immunofluorescence studies revealed the presence of PCT within monocytes. In the supernatants of monocyte cultures PCT was detectable under control conditions. Stimulation with lipopolysaccharide resulted in the increased PCT concentrations both in the supernatants of healthy and patient monocyte cultures. CONCLUSIONS: In the given patient PCT was superior to other inflammation markers with regard to early and progression diagnosis. Peripheral blood monocytes appear to be a potential site of inflammation-induced PCT production. For the first time intracellular distribution pattern and release of PCT from human monocytes was described. DISCUSSION: Based on the presented data broad clinical studies devoted to PCT evaluation in obstetric patients seem to be promising. As till now the interpretation of increased PCT values depended on empirical knowledge, extensive studies of the potential production site as well as its biological significance should be performed, too.

Abortion, Septic↗