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Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2003

Apical growth and mitosis are independent processes in Aspergillus nidulans.

It is well established that cytoplasmic microtubules are depolymerized during nuclear division and reassembled as mitotic microtubules. Mounting evidence showing that cytoplasmic microtubules were also involved in apical growth of fungal hyphae posed the question of whether apical growth became disrupted during nuclear division. We conducted simultaneous observations of mitosis (fluorescence microscopy) and apical growth (phase-contrast microscopy) in single hyphae of Aspergillus nidulans to determine if the key parameters of apical growth (elongation rate and Spitzenkörper behavior) were affected during mitosis. To visualize nuclei during mitosis, we used a strain of A. nidulans, SRS27, in which nuclei are labeled with the green-fluorescent protein. To reveal the Spitzenkörper and measure growth with utmost precision, we used computer-enhanced videomicroscopy. Our analysis showed that there is no disruption of apical growth during mitosis. There was no decrease in the rate of hyphal elongation or any alteration in Spitzenkörper presence before, during, or after mitosis. Our findings suggest that apical growth and mitosis do not compete for internal cellular resources. Presumably, the population of cytoplasmic microtubules involved in apical growth operates independently of that involved in mitosis.

Aspergillus nidulans↗
PubMed2003

[Toleration of high altitudes by patients with heart and pulmonary diseases].

The decisive limiting parameter in such patients is the lower oxygen partial pressure in inhaled air. It is, however, still possible for patients with coronary heart disease, high blood pressure or bronchial asthma to tolerate high altitudes without having to experience health problems. Prerequisites, however, are adequate acclimatization, optimal medication and pre-travel stable status. In addition, patients must be informed about emergency measures and how to recognize high-altitude sickness. To prevent pneumothorax leading to rapid decompression during flights, particular attention must be addressed to the problem of trapped air in patients with emphysema or cystic fibrosis.

Acclimatization↗
PubMed2003

Multi- and monofractal indices of short-term heart rate variability.

Indices of heart rate variability (HRV) based on fractal signal models have recently been shown to possess value as predictors of mortality in specific patient populations. To develop more powerful clinical indices of HRV based on a fractal signal model, the study investigated two HRV indices based on a monofractal signal model called fractional Brownian motion and an index based on a multifractal signal model called multifractional Brownian motion. The performance of the indices was compared with an HRV index in common clinical use. To compare the indices, 18 normal subjects were subjected to postural changes, and the indices were compared on their ability to respond to the resulting autonomic events in HRV recordings. The magnitude of the response to postural change (normalised by the measurement variability) was assessed by analysis of variance and multiple comparison testing. Four HRV indices were investigated for this study: the standard deviation of all normal R-R intervals; an HRV index commonly used in the clinic; detrended fluctuation analysis, an HRV index found to be the most powerful predictor of mortality in a study of patients with depressed left ventricular function; an HRV index developed using the maximum likelihood estimation (MLE) technique for a monofractal signal model; and an HRV index developed for the analysis of multifractional Brownian motion signals. The HRV index based on the MLE technique was found to respond most strongly to the induced postural changes (95% CI). The magnitude of its response (normalised by the measurement variability) was at least 25% greater than any of the other indices tested.

Electrocardiography↗
PubMed2003

Molecular farming of recombinant antibodies in plants.

Antibodies represent a large proportion of therapeutic drugs currently in development. In most cases, they are produced in mammalian cell lines or transgenic animals because these have been shown to fold and assemble the proteins correctly and generate authentic glycosylation patterns. However, such expression systems are expensive, difficult to scale up and there are safety concerns due to potential contamination with pathogenic organisms or oncogenic DNA sequences. Plants represent an inexpensive, efficient and safe alternative for the production of recombinant antibodies. Research over the last 10 years has shown that plants can produce a variety of functional antibodies and there is now intense interest in scaling up production to commercial levels. In this review, we discuss the advantages of plants over traditional expression systems, describe how antibody expression in plants is achieved and optimized and then consider the practical issues concerning large-scale molecular farming in plants. The first plant-produced therapeutic antibodies are already in clinical trials, and, given the economic benefits of this production system, we are likely to see many more recombinant antibodies produced in this manner in the future.

Animals↗
PubMed2003

[Stage 3 recommendations--the early recognition of breast cancer in Germany. Abridged version for medical practitioners].

The Aim of this level 3 good clinical practice guideline is to help physicians, women and patients in decision making about the appropriate health care for early detection of breast cancer. The principle of early detection of breast cancer comprise the detection and diagnosis of premalignant breast tumors (stage 0, Carcinoma in situ), risk reduction of cancer development as well as the detection and diagnosis of breast cancer at an early stage (stage I), with a 90% chance of cure as shown by a large number of clinical trials. To establish a nation wide, comprehensive quality assuring program for the early detection of breast cancer the guideline summarized in the following paper offers the basis for a timely mortality reduction of breast cancer. The cure of early stage disease will be additionally possible by less invasive treatment allowing patients to maintain quality of life. The guideline leads to a major improvement of women's health care.

Adult↗
PubMed2003

Perceived risk of bovine spongiform encephalopathy and dietary behavior.

The German BSE crisis in early 2001 can be considered as a natural experiment with strong behavioral consequences. The present study investigated psychological and other factors associated with reduced meat consumption compared to the first months of the previous year. As expected, all types of meat, with the exception of poultry and game, were eaten less often. The effect was strongest in beef, where almost half of the sample reported reduced meat consumption. As predicted by the health belief model, perceived threat was associated with subjective vulnerability. It was not, however, strongly associated with perceived seriousness of BSE, probably due to the ubiquitous public discussion of the topic. Reduced beef consumption has three to four times more frequent in the event of subjective threat.

Adolescent↗
PubMed2002

Bioprocess applications of a Sindbis virus-based temperature-inducible expression system.

The production and study of toxic proteins requires inducible expression systems with low basal level expression and high inducibility. Here, we describe bioprocess applications of the pCytTS temperature-regulatable Sindbis virus replicon-based expression system. We used green fluorescent protein as a marker protein to optimize the selection of stable transfected clones with increased expression levels. Using the optimized protocol, clones were constructed that produced the growth-inhibiting, anti-viral protein interferon beta (beta-IFN). Selected clones were analyzed for temperature-dependent beta-IFN production in adherent and suspension cultures in serum free medium. Specific expression levels were around 1.0 x 10(5) IU/10(6) cells/day (0.5 microg/10(6) cells/day) in suspension cultures and over 1.5 x 10(6) IU/mL/day (7.5 microg/mL/day) in hollow fiber reactors using adherent cells. Hexahistidine-tagged beta-IFN purified from T-flask cultures was highly glycosylated and showed high specific activity. beta-IFN mRNA amplified by the viral replicase for 10 days did not show an accumulation of mutations. These data suggest the applicability of the pCytTS-inducible expression system for the production of high-quality glycoproteins in different reactors.

Animals↗
PubMed2002

Depth profiles and resolution limits in accelerator-based solid state analysis.

A ubiquitous problem in solid state analysis is the determination of the elemental composition of a sample as a function of the depth. The determination of the depth profiles from ion-beam experiments is an ill-posed inversion problem due to ion-beam and detector-induced energy spreads as well as energy-loss straggling and small-angle scattering effects. The inversion problem is solved in the framework of Bayesian probability theory, which provides a method for quantifying and combining uncertain data and uncertain additional information. By deconvolving the apparatus transfer function and modeling the scattering events in the sample we reconstructed depth profiles of (13)C in tetrahedral amorphous carbon (ta-C) and depth profiles in (12)C/(13)C marker probes. An enhancement of the energy resolution by a factor of 6 was obtained.

Journal Article↗
PubMed2002

Socio-economic outcome of paraplegia compared to lower limb amputation.

STUDY DESIGN: The socio-economic outcome was retrospectively compared between patients with traumatic lower limb amputation and those with paraplegia due to a spinal cord injury (SCI). OBJECTIVE: To evaluate the effect of specific rehabilitative procedures on the socio-economic outcome. SETTING: Paraplegic Centre at the University Hospital in Zurich, Switzerland. METHODS: Accidents occurring in a collective of 1.9 million persons in Switzerland over 3 years were included in the study. Fifty-six persons with unilateral amputation of lower limbs were compared with 54 persons with paraplegia. The follow-up was assessed over 5 years. RESULTS: The following data was obtained in patients with amputations compared to those with SCI (median values): (1) hospital stay: 150 versus 164 days; (2) the work was taken up after 689 versus 616 days; (3) the global average case costs amounted to SFr. 491.000 versus SFr. 606.000 during the first 5 years after injury; (4) the permanent degree of disability was determined to 40% versus 42%. Except for the global costs, all differences were not significant. CONCLUSIONS: There are only a few differences between the socio-economic outcomes between patients with lower limb amputations and those with paraplegia. It remains unclear if the highly specialised rehabilitation services provided for patients with SCI accounts for the similarity since individuals with SCI have additional neurogenic dysfunction of the bladder and bowel. Alternatively, the data may suggest a need for greater rehabilitation services for amputees or may reflect a threshold effect in rehabilitation outcomes.

Adolescent↗
PubMed2002

Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate.

Patients with reflux esophagitis (grade II or III, Savary-Miller, intention-to-treat, n=256, age range 19-82 years) were randomly assigned to a double-blind, double-dummy treatment with either pantoprazole 40 mg once daily or ranitidine 150 mg twice daily. After 4 weeks, each patient was clinically and endoscopically assessed. Failure to heal required a further 4 weeks of treatment and a new evaluation thereafter. After 4 weeks, healing of lesions was confirmed in 63% (69 out of 109) of patients receiving pantoprazole and in 22% (25 out of 113) receiving ranitidine (P < 0.001, per protocol population). After 8 weeks, the cumulative healing rates were 88% and 46%, respectively (P < 0.001). Complete freedom from esophagitis-related symptoms (acid eructation, heartburn, pain while swallowing) was greater in the pantoprazole than in ranitidine group after 2 and 4 weeks (74% vs. 47%; 87% vs. 52%, respectively, P < 0.001). After 4 weeks, the healing rate was 76% in Helicobacter pylori (Hp)-positive vs. 45% in Hp-negative patients treated with pantoprazole (P < 0.01). The Hp status did not influence healing rates in patients treated with ranitidine. The most frequent adverse events in the pantoprazole group were diarrhea and somnolence (2-3% of patients), and in the ranitidine group, headache, diarrhea, dizziness, increase of liver enzymes and pruritus (2-4% of patients). In conclusion, pantoprazole was more effective than ranitidine in the healing rate and relief from reflux esophagitis-associated symptoms, and Hp infection was associated with higher healing rate during therapy with pantoprazole but not with ranitidine.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

[Evalutation of health monitoring in Bavaria by computer-assisted telephone interviews (CATI) in comparison to the German National Health Examination Survey conducted in 1998 by the Robert Koch Institute].

Between June 1999 and May 2000, 2051 residents of Bavaria were interviewed on health and health-related behaviour. The objective of the study was to assess the representativeness and validity of data acquired by computer-assisted telephone interviewing (CATI) as compared to results of the German National Health Examination Survey 1998. The following variables showed excellent agreement: subjective health status, lifetime disease prevalences, such as myocardial infarction, stroke, cancer, asthma, diabetes, hypertension, hypercholesterolaemia, utilisation of medical services, and smoking habits (prevalence of present and former smoking, average cigarette consumption per day). Minor differences were found with respect to the frequency of consulting naturopathic doctors. Self-reported anthropometric data from the present study differed considerably from the results of the objective measurements during the German Health Survey. We conclude that, in terms of data quality, CATI compares well with traditional methods such as face-to-face interviewing or mailed questionnaires. In view of several practical advantages of the method, we recommend CATI as a future basic methodology of a German health surveillance system consisting of different coordinated health data collections.

Adolescent↗
PubMed2002

Efficacy of plant-produced recombinant antibodies against HCG.

BACKGROUND: Antibody engineering facilitates the construction of different antibody formats [single chain variable fragment (scFv), diabody, full-size chimeric monoclonal antibody] with ease. METHODS: We constructed recombinant antibodies against HCG, which is widely used in pregnancy testing and is also produced by a number of cancers. RESULTS: The recombinant antibodies were transiently expressed in tobacco leaves to levels of up to 40 mg of pure protein per kg fresh leaf weight. Enzyme linked immunosorbent assay (ELISA) and electrophoretic mobility assay (EMSA) confirmed antibody specificity for the beta subunit of beta-HCG. The efficacy was confirmed by inhibiting HCG induced testosterone production by Leydig cells in vitro and by blocking the HCG induced increase in mouse uterine weight in vivo. CONCLUSIONS: Passive immunization with recombinant HCG-specific antibodies may have clinical utility as (i) diagnostic and therapeutic tools for HCG-expressing cancers and (ii) contraceptive measures.

Animals↗
PubMed2001

Discovery and evaluation of piperidinyl carboxylic acid derivatives as potent alpha(4)beta(1) integrin antagonists.

Piperidinyl carboxylic acid-based derivatives were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the alpha(4)beta(1) integrin (VLA-4, very late antigen 4) and the vascular cell adhesion molecule 1 (VCAM-1). Compounds 2a-h inhibited the adhesion in a cell-based assay in the low and sub micromolar range, a pharmacokinetic study of 2d is reported.

Area Under Curve↗
PubMed2001

Aspergillus nidulans DigA, a potential homolog of Saccharomyces cerevisiae Pep3 (Vps18), is required for nuclear migration, mitochondrial morphology and polarized growth.

The fungal vacuole is an acidic organelle that is involved in a variety of physiological processes, such as protein turnover, ion and pH homeostasis and osmoregulation. The function of the vacuole largely depends on vesicle transport providing the organelle with enzymes and substrates. The process of vesicle transportation has been studied best in Saccharomyces cerevisiae, where several proteins that are crucial for intracellular vesicle sorting have been identified. One such protein is Pep3 (Vps18). In pep3 mutants vacuole function and vacuole morphology are affected. We cloned the gene for a potential homolog of Pep3 from the filamentous fungus Aspergillus nidulans. The gene, digA (for dichotomous growth), was identified in a screen for nuclear migration mutants. A. nidulans digA encodes a protein of 108.3 kDa, which includes a 122-amino acid clathrin repeat motif, two short coiled-coil regions, and a RING finger Zn-binding motif at the C-terminus. All three sequence motifs suggest interaction of DigA with other proteins. DigA is 25% identical to a homolog from Schizosaccharomyces pombe, 23% to a protein from human, 21% to the product of the Drosophila melanogaster gene deep orange (dor) and 18% to S. cerevisiae Pep3 (Vps18). We localized DigA as a HA-epitope-tagged protein in the cytoplasm of A. nidulans vegetative cells, by secondary immunofluorescence. A digA mutant displays a pleiotropic phenotype with clustered mitochondria, clustered nuclei and a defect in polarization of the actin cytoskeleton. These results suggest that vacuolar functions are required for organelle positioning and polarized growth.

Adaptor Proteins, Vesicular Transport↗
PubMed2001

Analysis of single-chain antibody production in Pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations.

In the last few years the Pichia pastoris expression system has been gaining more and more interest for the expression of recombinant proteins. Many groups have employed fermentation technology in their investigations because the system is fairly easy to scale up and suitable for the production in the milligram to gram range. A large number of heterologous proteins from different sources has been expressed, but the fermentation process technology has been investigated to a lesser extent. A large number of fermentations are carried out in standard bioreactors that may be insufficiently equipped to meet the demands of high-cell-density fermentations of methylotrophic yeasts. In particular, the lack of on-line methanol analysis leads to fermentation protocols that may impair the optimal expression of the desired products. We have used a commercially available methanol sensor to investigate in detail the effects of supplementary glycerol feeding while maintaining a constant methanol concentration during the induction of a Mut(+) strain of Pichia pastoris. Specific glycerol feed rates in the range of 38-4.2 mg. g(-1). h(-1) (mg glycerol per gram fresh weight per hour) were investigated. Expression of the recombinant scFv antibody fragment was only observed at specific feed rates below 6 mg. g(-1). h(-1). At low specific feed rates, growth was even lower than with methanol as the sole carbon source and the harvest expression level of the scFv was only half of that found in the control fermentation. These results show that glycerol inhibits expression driven by the AOX1 promoter even at extremely limited availability and demonstrate the benefits of on-line methanol control in Pichia fermentation research.

Bioreactors↗
PubMed2001

The inhibitory effect of IL-1 beta on IL-6-induced alpha 2-macroglobulin expression is due to activation of NF-kappa B.

The cross-talk between the signal transduction of simultaneous acting cytokines largely determines the final impact of cytokines on their target genes. Both NF-kappaB and STAT3 are transcription factors well known to be activated by many stimuli and to mediate transcriptional activation by binding to specific enhancer sequences. In this study, it is analyzed how IL-1beta inhibits IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. It is shown that IL-1beta prevents STAT3 binding to the two STAT3-responsive sites within the alpha(2)-macroglobulin promoter by association of IL-1beta-activated NF-kappaB to this region. The observation that inhibition of IL-6-induced transcriptional activation of this promoter by IL-1beta is reversed by cotransfection with I-kappaBalpha provides evidence that NF-kappaB activation by IL-1beta is responsible for inhibition of IL-6-mediated trans activation of the alpha(2)-macroglobulin gene. Accordingly, cotransfection of the NF-kappaB subunits p50 or p65 themselves inhibited activation of the alpha(2)-macroglobulin promoter by IL-6. Introduction of point mutations in each of the two NF-kappaB sites overlapping the two STAT3 binding sites within the alpha(2)-macroglobulin promoter provides evidence that each of these two sites counteracts transcriptional activation via STAT3. Most interestingly, at least one functional NF-kappaB consensus site is essential for the IL-6-induced transcriptional activation of the alpha(2)-macroglobulin promoter. Additional data are provided indicating that the activation of NF-kappaB by IL-1beta is also responsible for the inhibition of other IL-6-inducible genes, such as the alpha(1)-antichymotrypsin gene as well as the suppressor of cytokine signaling 3 gene, suggesting a more general relevance of this mechanism for transcriptional regulation.

Animals↗