Biomedical subjects

R Fuchs

Publications and source records attributed to R Fuchs.

At least 19 recordsLinked to original sources

PubMed2006

[Preoperative psychoeducation for a severely traumatized child].

N., an 8-year-old girl with a long term history of severe sexual abuse and maltreatment with consecutive mental disorders, was scheduled for surgery of clubfeet. The team consisting of an anesthesiologist, a psychologist and a pediatrician decided to prepare the girl for surgery without time pressure. In a first step we applied psychoeducation to obtain a certain degree of confidence. Psychoeducation is a special form of psychological treatment aiming to define cause and goal of surgery together with the patient and relatives. In a further step the anesthesiologist familiarized her with the surgical procedure and the operating theatre. Finally a careful anesthesia with a pain-free postoperative period was applied. Even extremely traumatized children can be prepared for surgery by the help of psychoeducative methods, without time pressure, a careful and pain-free anesthesia and an experienced team of doctors.

Anesthesia↗

PubMed2005

Efficient apical IgG recycling and apical-to-basolateral transcytosis in polarized BeWo cells overexpressing hFcRn.

The human neonatal Fcgamma-receptor (hFcRn) involved in overall maternal-fetal IgG transmission is expressed in placental villous syncytiotrophoblast. However, the role of hFcRn in IgG transport and trafficking across this cell layer is poorly characterized. To gain insight into this mechanism we have overexpressed functional hFcRn in trophoblast-derived BeWo cells (BeWo/hFcRn cells) [Ellinger I, Reischer H, Lehner C, Leitner K, Hunziker W, Fuchs R. Placenta 2005;26:171-82] since parental BeWo cells endogenously express low levels of the receptor. We now demonstrate that hFcRn overexpression differentially affected apical-to-basolateral transcytosis and apical recycling: whereas IgG transcytosis was reduced by 35%, IgG recycling was stimulated by 100% as compared to parental cells, indicating that hFcRn plays a role in both processes. The endosomal compartments involved in hFcRn/IgG transport after apical IgG internalization were then analyzed by confocal immunofluorescence microscopy using compartment specific markers. hFcRn/IgG were found in apical early endosomes, in transferrin recycling compartments and in vesicles near the basolateral plasma membrane, presumably transcytotic vesicles. Neither hFcRn nor IgG was routed to the degradative pathway to lysosomes. These transport and localization data are in accordance with efficient hFcRn-mediated apical IgG recycling and basolateral directed IgG transcytosis in placental trophoblasts.

Cell Membrane↗

PubMed2005

Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.

PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214). RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.

Adult↗

PubMed2005

The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.

The 8p11 myeloproliferative syndrome (EMS) also known as stem cell leukemia-lymphoma syndrome (SCLL) is associated with translocations that disrupt FGFR1. The resultant fusion proteins are constitutively active tyrosine kinases, and different FGFR1 fusions are associated with subtly different disease phenotypes. We report here a patient with a t(8;17)(p11;q23) and an unusual myelodysplastic/myeloproliferative disease (MDS/MPD) characterized by thrombocytopenia due to markedly reduced size and numbers of megakaryocytes, with elevated numbers of monocytes, eosinophils and basophils. A novel mRNA fusion between exon 32 of the myosin XVIIIA gene (MYO18A) at chromosome band 17q11 and exon 9 of FGFR1 was identified. Partial characterization of the genomic breakpoints in combination of bubble-PCR with fluorescence in situ hybridization revealed that the t(8;17) arose from a three-way translocation with breaks at 8p11, 17q11 and 17q23. MYO18A-FGFR1 is structurally similar to other fusion tyrosine kinases and is likely to be the causative transforming lesion in this unusual MDS/MPD.

Aged↗

PubMed2005

Ochratoxin A in human kidney diseases.

Ochratoxin A (OTA) is an ubiquitous nephrotoxic and carcinogenic mycotoxin considered to be involved in the aetiology of Balkan endemic nephropathy (BEN). The occurrence of this human fatal disease that appears in regions of Bosnia and Herzegovina, Bulgaria, Croatia, Rumania, and Serbia and Monte Negro correlates with very high incidence of otherwise rare urothelial tumours of the renal pelvis and ureters. Although OTA was found more frequently and/or in higher concentration in food and blood of inhabitants in regions with BEN than in other regions, the involvement of OTA in the development of BEN is still open. Patients with chronic renal insufficiency treated with dialysis have higher blood OTA concentrations than healthy persons, and OTA concentration does not decrease with such treatment.

Balkan Nephropathy↗

PubMed2003

Fluorescent Pseudomonas mainly produce the dihydro form of pyoverdine at low specific growth rate.

AIMS: To analyse the influence of cell growth rate and iron concentration on the production of pyoverdines (PVDs) and of their reduced dihydro forms by three fluorescent Pseudomonas strains (P. putida BTP16, P. fluorescens BTP7 and P. aeruginosa 7NSK2). METHODS: PVD and dihydropyoverdine (DHPVD) productions were determined by LC ESI-MS and spectrophotometry during batch and chemostat culture at different dilution rates. SIGNIFICANCE: The relatively high PVD-to-DHPVD ratio (0.57) observed in pH-controlled batch cultures suggested that a base-catalysed chemical oxidation of the dihydroform is not the prime mechanism involved in generating PVDs. Interestingly, in chemostat cultures the PVD-to-DHPVD ratio was significantly reduced at low specific growth rate. Our results suggest that the oxidation of DHPVD to PVD is catalysed by an iron-dependent enzymatic reaction rather than a chemical oxidation.

Biomass↗

PubMed2003

Changes in plasma lipids after a non-lethal dose of cycloheximide in rats.

This paper describes a study of the effect of a single intraperitoneal non-lethal dose of cycloheximide (CHM; 2.0 mg/kg body weight) on the concentration of plasma lipids and lipoproteins in male rats killed one, two, three, four and nine days after receiving the dose. The concentration of triglycerides, total cholesterol, high-density lipoproteins (HDL)-cholesterol and low-density lipoproteins (LDL)-cholesterol was measured in treated and control animals. The effect of CHM on the concentration of triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol was visible in rat plasma throughout the study. Total cholesterol and HDL-cholesterol concentrations showed the same pattern of changes, probably due to the reversible inhibition of apolipoprotein apo A-I synthesis by CHM. The concentration of triglycerides decreased after a lag period of three days when the reserves of apolipoprotein apo B, the main apolipoprotein of very low-density lipoproteins (VLDL)-cholesterols produced in the liver, were consumed.

Animals↗

PubMed2001

Apical to basolateral transcytosis and apical recycling of immunoglobulin G in trophoblast-derived BeWo cells: effects of low temperature, nocodazole, and cytochalasin D.

The murine neonatal Fc receptor, FcRn, carries out two functions: materno-fetal IgG delivery and maintenance of serum IgG homeostasis. During human pregnancy maternal IgG is transferred across placental syncytiotrophoblasts presumably by the human homolog of FcRn, hFcRn. Trophoblast-derived BeWo cells express hFcRn endogenously and can be considered as a model system to investigate IgG transport in syncytiotrophoblasts. Using a pulse-chase protocol, we here demonstrate that polarized BeWo cells exhibit not only apical to basolateral transcytosis but also apical IgG recycling. Thus, for the first time we demonstrate that epithelial cells can be involved in both materno-fetal IgG transmission and regulation of serum IgG levels. Lowering the temperature from 37 to 16 degrees C reduced, but did not block, IgG recycling and transcytosis. Microtubule-disruption by nocodazole did not influence transcytosis or apical recycling. Disassembly of filamentous actin by cytochalasin D stimulated apical endocytosis and recycling, while transcytosis remained unaffected. In summary, in BeWo cells apically internalized IgG enters both a transcytotic and recycling pathway. While the transcytotic route is temperature-sensitive but independent from microtubules and actin filaments, the apical recycling pathway is temperature-influenced and stimulated by actin disassembly, suggestive for the involvement of distinct endosome subcompartments in transcytosis and recycling.

Antineoplastic Agents↗

PubMed2001

Non-destructive NIR-FT-Raman analyses in practice. Part I. Analyses of plants and historic textiles.

Non-destructive analysis of natural substances in plants as well as of old dyed textiles by Raman spectroscopy has not been possible using conventional techniques. Exciting lines from the visible part of the spectrum produced photochemical and thermal decomposition of the objects as well as strong fluorescence. Using Nd:YAG laser excitation at 1,064 nm together with a special sample arrangement and interferometric recording, various polyacetylenes in Aethusa cynapium and in chamomile (Chamomilla recutita) and the main valuable substances in gentian species (Gentiana lutea and G. punctata), curcuma roots (Curcuma longa), cinnamon (Cinnamomum zeylanicum), fennel (Foeniculum vulgare), clove (Caryophyllus aromaticus), and ginger (Zingiber officinale) were analyzed non-destructively and discussed in comparison with the corresponding pure standard compounds. We further analyzed non-destructively the FT Raman spectra of collections of historical textiles and lakes used for dyeing. It is possible to distinguish the main dye component non-destructively by using Raman bands.

Biological Factors↗

PubMed2001

The structure of a pyoverdine produced by a Pseudomonas tolaasii-like isolate.

Cultures of Agaricus bisporus, the most extensively cultivated mushroom, can be infected severely by Pseudomonas tolaasii. This pathogen is characterized by the so-called white line reaction, a precipitate formed on agar plates between its colonies and those of P. reactans, both belonging to the collective species P. fluorescens. A recent study has shown that a group of P. tolaasii isolates can be subdivided into two groups or 'siderovars', based on the pyoverdines they produce (Munsch et al. 2000). One group of strains is characterized by the pyoverdine described by Demange et al. (1990). A representative of the second group (strain Ps3a) was found to produce the same pyoverdine as a strain which had been classified before as P. aureofaciens. However, based mainly on 16S rRNA gene sequence comparisons and REP-PCR generated fingerprints, the two strains are not identical. They are also distinguishable from the P. tolaasii type strain.

Agaricales↗

PubMed2001

Elevated endosomal pH in HeLa cells overexpressing mutant dynamin can affect infection by pH-sensitive viruses.

Many viruses gain access to the cell via the endosomal route and require low endosomal pH for infectivity. The GTPase dynamin is essential for clathrin-dependent endocytosis, and in HeLa cells overexpressing the nonfunctional dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a human minor group rhinovirus, is internalized by members of the low-density lipoprotein receptor family in a clathrin-independent manner. The low endosomal pH then leads to conversion of the capsid to C-antigen, which is required for release (uncoating) and transfer of the viral RNA into the cytosol and de novo synthesis of infectious virus. We here demonstrate that overexpression of dynaminK44A reduces this antigenic conversion and results in diminished viral synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence, HRV2 uncoating is diminished early after internalization but attains control levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in addition to trafficking defects, results in an elevated endosomal pH and thereby affects virus infection and most likely endosomal sorting and processing.

Binding Sites↗

PubMed2001

[Smoking behavior and alcohol drinking in students in a rural area of East Germany].

The present investigation ("Torgau Study") provides epidemiological information on a target population which in the past has hardly been in the focus of health promotion activities: the subgroup of children and adolescents of rural regions in Eastern Germany. A total survey was conducted that encompassed all classes from grade 6 to 10 of all schools in the district of Torgau (Saxony). Together, 5,925 students in the age range 12 to 16 years participated in this study (participation rate: 81.3%). The results provide a differentiated picture of their smoking behavior and alcohol use broken down by gender, school-type and grade. With respect to smoking the data show that the prevalence of regular smokers (i.e., daily smokers) in grade 10 is 41% in the Mittelschule (the school-type with a stronger vocational orientation) and 29% in the Gymnasium (the school-type with a university-preparatory curriculum). 51.9% of all students report that at least one parent smokes. There is a highly significant association between smoking status of the parents and smoking status of their children. The analysis of reasons for smoking highlight the stepwise transition into nicotine dependency from a psychological perspective. Most of the adolescents (about 80%) know about the dangers of passive smoking. However, with increasing age this knowledge loses its subjective relevance because dissonance-reducing strategies are applied ("doesn't matter"-attitude). Among girls, even in grade 10, there are almost no daily alcohol consumers (less than 1%); among boys in grade 10 the rate of daily alcohol users is about 8%. The rate of those 10th graders who consume alcoholic beverages at least once a week is however 30.6% (girls: 18.7%; boys: 44.2%). The longer the alcohol experience the more specific become the social and emotional motives for drinking. Altogether, the results suggest that efforts to prevent substance misuse in the rural regions of Eastern Germany are as necessary as in other regions. But the time has come that innovative approaches of drug prevention that are implemented and evaluated mostly in the bigger cities should also be started in the rural regions (not only of Eastern Germany), and should be adapted to the specific conditions there.

Adolescent↗

PubMed2001

[Do baseline haemoglobin-rates point to the efficacy of blood saving techniques?].

OBJECTIVE: We tested the hypothesis that blood saving techniques are more effective in patients with a low baseline haemoglobin. METHODS: We analysed retrospectively 1665 total hip replacements and 848 total knee replacements. Patients were divided in three groups according to the baseline haemoglobin (Hb): Group A were patients with a Hb of more than 15 g/dl, group B between 15 g/dl and 13 g/dl and group C with a Hb of less than 13 g/dl. The blood saving techniques applied (Preoperative blood donation, isovolemic haemodilution, and mechanical autotransfusion) aimed to a high patient population which underwent surgery without transfusion of homologous blood. RESULTS: The higher the baseline value of haemoglobin the higher was the patient population without homologous blood transfusion. The lower the Hb the higher was the effectiveness of blood saving techniques. In case of total hip replacement preoperative blood donation increased the patient population without homologous blood transfusion in all three groups significantly. However, in case of total knee replacement preoperative blood donation increased the patient population without homologous blood transfusion only in group B and C significantly. In both surgical procedures the combination of preoperative blood donation with other blood saving techniques did not further increase the patient population without homologous blood transfusion. In total hip replacement mechanical autotransfusion as well as isovolemic haemodilution reduced homologous transfusion in patients with low baseline haemoglobin. However, the increase was more pronounced when both techniques were combined. CONCLUSION: From our data is derived that the likelihood of homologous blood transfusion is greater in patients with a low baseline haemoglobin. However, in case of hip arthroplasty patients with a high baseline haemoglobin also profit from blood saving techniques while in case of knee arthroplasty the efficiency of blood saving techniques in a patient population with a high baseline haemoglobin is negligible. It seems to make sense to evaluate for the different kinds of surgery those patients who profit most from the different blood saving techniques.

Arthroplasty, Replacement, Hip↗

PubMed2001

Bayesian estimation of fold-changes in the analysis of gene expression: the PFOLD algorithm.

A general and detailed noise model for the DNA microarray measurement of gene expression is presented and used to derive a Bayesian estimation scheme for expression ratios, implemented in a program called PFOLD, which provides not only an estimate of the fold-change in gene expression, but also confidence limits for the change and a P-value quantifying the significance of the change. Although the focus is on oligonucleotide microarray technologies, the scheme can also be applied to cDNA based technologies if parameters for the noise model are provided. The model unifies estimation for all signals in that it provides a seamless transition from very low to very high signal-to-noise ratios, an essential feature for current microarray technologies for which the median signal-to-noise ratios are always moderate. The dual use, as decision statistics in a two-dimensional space, of the P-value and the fold-change is shown to be effective in the ubiquitous problem of detecting changing genes against a background of unchanging genes, leading to markedly higher sensitivities, at equal selectivity, than detection and selection based on the fold-change alone, a current practice until now.

Algorithms↗

PubMed2001

Analysis of temporal gene expression profiles: clustering by simulated annealing and determining the optimal number of clusters.

MOTIVATION: Cluster analysis of genome-wide expression data from DNA microarray hybridization studies has proved to be a useful tool for identifying biologically relevant groupings of genes and samples. In the present paper, we focus on several important issues related to clustering algorithms that have not yet been fully studied. RESULTS: We describe a simple and robust algorithm for the clustering of temporal gene expression profiles that is based on the simulated annealing procedure. In general, this algorithm guarantees to eventually find the globally optimal distribution of genes over clusters. We introduce an iterative scheme that serves to evaluate quantitatively the optimal number of clusters for each specific data set. The scheme is based on standard approaches used in regular statistical tests. The basic idea is to organize the search of the optimal number of clusters simultaneously with the optimization of the distribution of genes over clusters. The efficiency of the proposed algorithm has been evaluated by means of a reverse engineering experiment, that is, a situation in which the correct distribution of genes over clusters is known a priori. The employment of this statistically rigorous test has shown that our algorithm places greater than 90% genes into correct clusters. Finally, the algorithm has been tested on real gene expression data (expression changes during yeast cell cycle) for which the fundamental patterns of gene expression and the assignment of genes to clusters are well understood from numerous previous studies.

Algorithms↗

PubMed2001

Placental alkaline phosphatase expression at the apical and basal plasma membrane in term villous trophoblasts.

Human placental alkaline phosphatase (PLAP) was localized at the apical and basal plasma membrane of syncytiotrophoblasts and at the surface of cytotrophoblasts in term chorionic villi using immunoelectron microscopy. Similarly, apical and basolateral PLAP expression was found in polarized trophoblast-derived BeWo cells. Trophoblasts isolated from term placentas exhibited mainly vesicular PLAP immunofluorescence staining immediately after isolation. After in vitro differentiation into syncytia, PLAP plasma membrane expression was upregulated and exceeded that observed in mononuclear trophoblasts. These data call for caution in using PLAP as a morphological marker to differentiate syncytiotrophoblasts from cytotrophoblasts or as a marker enzyme for placental brush-border membranes. (J Histochem Cytochem 49:1155-1164, 2001)

Alkaline Phosphatase↗

PubMed2001

Influence of culture conditions on lipopeptide production by Bacillus subtilis.

Bacillus subtilis produces various families of lipopeptides with different homologous compounds. To produce "new molecules" with improved activities and to select strains that produced a reduced number of homologs or isomers, we studied the effects of different media on the nature of the synthesis of fatty acid chains for each lipopeptide family. This study focused on two B. subtilis strains cultivated in flasks. Optimized medium for lipopeptide production and Landy medium modified by replacing glutamic acid with other alpha-amino acids were used. We found that the intensity of production of homologous compounds depends on the strain and the culture medium. Analysis of these lipopeptides by high-performance liquid chromatography showed that the strain B. subtilis NT02 yielded various homologous compounds when cultivated in Landy medium (L-Glu), but primarily one homologous product in high relative amounts when cultivated in the optimized medium. Mass spectrometric analysis and determination of the amino acid composition of this molecule enabled us to identify it as Bacillomycine L c15.

Amino Acids↗

PubMed2001

Siderotyping--a powerful tool for the characterization of pyoverdines.

Tools for the identification of bacteria are of great importance especially for taxonomical and medical purposes. In the case of fluorescent pseudomonads a quick and unambiguous identification is possible by methods that are referred to as "siderotyping". All of them are based upon the characterization of the bacterial siderophores or the receptors expressed for the uptake of these compounds. Different microbiological and bioanalytical tests that are accurate, rapid and easy to use will be described.

Isoelectric Focusing↗