Biomedical subjects

R Ulrich

Publications and source records attributed to R Ulrich.

At least 37 records · Page 2Linked to original sources

PubMed2001

The hamster polyomavirus--a brief review of recent knowledge.

The hamster polyomavirus (HaPV) was first described in 1967 as a virus associated with skin epithelioma of the Syrian hamster. The tumors appear spontaneously in a hamster colony bred in Berlin-Buch (HaB). Virus particles isolated from skin epitheliomas cause lymphoma and leukemia when injected into newborn hamsters from a distinct colony bred in Potsdam, Germany (HaP). The viral genome has been totally sequenced and the overall genetic organization establishes HaPV as a member of the polyomaviruses. HaPV is a second example of an middle T (MT) antigen encoding polyomavirus and nucleotide sequence homologies designates the mouse polyomavirus (Py) as the closest relative. Lymphomas induced by HaPV in HaP hamsters do not contain virus particles but instead accumulate different amounts of nonrandomly deleted free and/or integrated viral genomes. Transgenic mice produced by microinjection of HaPV DNA into the pronucleus of fertilized eggs of Gat: NMRI mice developed both, epitheliomas and lymphomas. Both tumor types contain extrachromosomal DNA. HaPV DNA was found to replicate in hamster lymphoid and fibroblast cell lines. Fully reproductive cycles could be detected only in GD36 lymphoblastic leukemia cells. HaPV carries the full transforming properties of a polyomavirus in vitro. Immortalization of primary rat cells is essentially carried out by the HaPV large T (LT) antigen and coexpression of HaPV MT and HaPV small T (ST) antigen is required for full transformation of rat fibroblasts. The preferential binding of HaPV MT to c-Fyn, a Src family kinase, has been proposed as a mechanism leading to lymphoid malignancies. Heterologous expression of HaPV-VP1 allowed the formation of virus like particles (VLPs) resembling HaPV particles. The high flexibility of HaPV-VP1 for insertion of foreign peptides offers a broad range of potential applications, especially in vaccine development.

Animals↗

PubMed2001

First molecular evidence for Puumala hantavirus in Slovakia.

We report on the first Puumala hantavirus nucleotide sequence (strain Opina-916) amplified from a bank vole trapped in Slovakia, central Europe. Phylogenetic analysis of the S-segment sequence grouped the virus within the western/central European sublineage of Puumala virus. In the neighborhood of the rodent trapping site two cases of human infection by the Puumala virus were verified.

Animals↗

PubMed2001

In vitro human tissue models in risk assessment: report of a consensus-building workshop.

Advances in the technology of human cell and tissue culture and the increasing availability of human tissue for laboratory studies have led to the increased use of in vitro human tissue models in toxicology and pharmacodynamics studies and in quantitative modeling of metabolism, pharmacokinetic behavior, and transport. In recognition of the potential importance of such models in toxicological risk assessment, the Society of Toxicology sponsored a workshop to evaluate the current status of human cell and tissue models and to develop consensus recommendations on the use of such models to improve the scientific basis of risk assessment. This report summarizes the evaluation by invited experts and workshop attendees of the current status of such models for prediction of human metabolism and identification of drug-drug interactions, prediction of human toxicities, and quantitative modeling of pharmacokinetic and pharmaco-toxicodynamic behavior. Consensus recommendations for the application and improvement of current models are presented.

Cell Culture Techniques↗

PubMed2001

Locus of the redundant-signals effect in bimodal divided attention: a neurophysiological analysis.

We reanalyzed the data from the study of Lamarre, Busby, and Spidalieri (1983). In that study, the activity of single neurons in area 4 of the motor cortex was recorded during a bimodal detection task in which a monkey (Macaca mulatta) had to respond as quickly as possible to a visual or an auditory signal or to both (redundant trials). Manual responses on redundant trials were speeded by the presence of both signals, as is typically found. The times between signal onsets and the first changes in neuronal activity were also speeded by redundant signals, but there was no difference between redundant-signals and single-signal trials in the time between the change in neuronal activity and movement onset. These results suggest that late motor processes are not speeded by redundant signals in bimodal detection tasks.

Animals↗

PubMed2001

On the analysis of psychometric functions: the Spearman-Kärber method.

With computer simulations, we examined the performance of the Spearman-Kärber method for analyzing psychometric functions and compared this method with the standard technique of probit analysis. The Spearman-Kärber method was found to be superior in most cases. It generally yielded less biased and less variable estimates of the location and dispersion of a psychometric function, and it provided more power to detect differences in these parameters across experimental conditions. Moreover, the Spearman-Kärber method provided information about the skewness and higher moments of psychometric functions that is beyond the scope of probit analysis. These advantages of the Spearman-Kärber method suggest that it should often be used in preference to probit analysis for the analysis of observed psychometric functions.

Confidence Intervals↗

PubMed2001

Counting models of temporal discrimination.

A three-category task was employed to test counting models for temporal discrimination. Unlike former approaches, the present one is not based on Weber functions. Specifically, the proposed test does not require the implicit but, nevertheless, debatable assumption that the pulse rate of the internal clock is constant for different durations of the standard interval. Furthermore, the present approach does not necessitate specific distributional assumptions about the interpulse times. An experiment was conducted to evaluate the predictions of this generalized counting model. The results are consistent with predictions of the generalized counting model. A further analysis suggests that the pulse rate decreases as the duration of the standard interval increases.

Adult↗

PubMed2001

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species.

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381-935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans.

Adolescent↗

PubMed2001

Determination and multivariate statistical analysis of biochemical responses to environmental contaminants in feral freshwater fish Leuciscus cephalus, L.

Modulations of 11 prospective biochemical markers of impacts of aquatic pollutants in liver tissue of chub (Leuciscus cephalus), caught at several sampling sites of a river with various pollution types and rates, were matched against analytical data of concentrations of organochlorine compounds, polycyclic aromatic hydrocarbons (PAHs), and heavy metals. Multivariate principal component analysis (PCA) of the field data showed general patterns of biochemical responses to different types of pollutants and relationships among the biomarkers. Cytochrome P4501A-dependent 7-ethoxyresorufin O-deethylase (EROD) activity, inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin and structurally related planar compounds, was strongly enhanced in the more contaminated areas. Compared with polychlorinated aromatic hydrocarbons, PAHs did not contribute so significantly to EROD induction. Testosterone 6 beta- and 16 alpha-hydroxylase activities, as an expression of the cytochrome P4503A27, were slightly increased at several sites but were significantly decreased in samples from some heavily polluted areas. Recently, these activities have been suggested as potential biomarkers of exposure to contaminants that do not induce cytochrome P4501A. In this study, their inhibition or induction was not associated with a specific class of monitored contaminants, and selectivities of these modulations are still to be investigated. Similar modulations of the prospective biochemical indicators of oxidative stress, including microsomal glutathione S-transferase activity, cytosolic glutathione S-transferase with ethacrynic acid, and glutathione reductase, were demonstrated by PCA. The pattern of the modulations of the microsomal nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in vitro differed from the responses of the rest of oxidative stress parameters at some sampling sites. Further biochemical markers of oxidative stress under study, including in vivo lipid peroxidation, in vitro production of reactive oxygen species, and the concentration of metallothioneins did not correlate well with the concentrations of the contaminants. Principal component analysis demonstrated that the EROD activity, glutathione-dependent enzymes, and Fe(II)-enhanced lipid peroxidation formed a suitable battery of biomarkers of exposure.

Animals↗

PubMed2001

Clinical characterization of Dobrava hantavirus infections in Germany.

There is increasing evidence that Dobrava (DOBV) but not Hantaan (HTNV) hantavirus is a hemorrhagic fever with renal syndrome (HFRS) causing agent in Central Europe. However, only single clinical cases of HFRS due to acute DOBV infection have been described so far. We report on three male patients from a non-endemic hantavirus focus in Northern Germany who suffered from mild to moderate HFRS strongly resembling nephropathia epidemica. Serotyping by detection of hantavirus species-specific neutralizing antibodies revealed acute infections by the HTNV-related hantavirus DOBV in all three cases. Since DOBV infections in the Balkans frequently present as severe HFRS, our cases suggest that Central-European DOBV infections have a different, less severe clinical outcome. These differences in DOBV virulence towards humans might be due to the existence of different genetic lineages of DOBV.

Acute Disease↗

PubMed2001

Monitoring river sediments contaminated predominantly with polyaromatic hydrocarbons by chemical and in vitro bioassay techniques.

Extracts of sediment samples collected from the Morava River and its tributaries (Czech Republic) were examined for mutagenic, dioxin-like, and estrogenic activities. Moreover, the human leukemic HL-60 cell line was tested as a potential model for the detection of effects of environmental contaminants on cell proliferation and differentiation processes. Analytical data indicate that the sediments were contaminated predominantly with polycyclic aromatic hydrocarbons (PAHs) and phthalate esters. The sums of concentrations of 16 U.S. Environmental Protection Agency priority PAHs ranged from 0.8 to 13.2 micrograms/g and those of phthalates reached up to 3,000 ng/g, while only low levels of chlorinated hydrocarbons were found. The main goal of the present study was to determine effects of PAH prevalence on in vitro bioassays, with special emphasis on dioxin-like activity. The dioxin-like activity was tested using a reporter gene assay based on chemical-activated luciferase expression (the CALUX assay). Significant dioxin-like activity (2.6-40.1 micrograms/g benzo[a]pyrene equivalents and 5.9-48.2 ng/g 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents) was detected in all samples, and the results obtained with various exposure times or with both crude and PAH-deprived extracts indicate that the response was probably caused almost exclusively by the presence of high concentrations of PAHs. This corresponds with results of chemical analyses and indicates that various exposure times would allow a discrimination between dioxin-like activities of persistent compounds and easily metabolized aryl hydrocarbon (Ah) receptor inducers. Only sediment extracts containing the highest concentrations of PAHs were mutagenic, as determined by the umu assay. Estrogenic activity was found in several samples (4.75-22.61 pg/g estradiol equivalents) using cells stably transfected with an estrogen-responsive element linked to a luciferase promoter. Noncytotoxic doses of extracts had no effects on HL-60 cell proliferation, while two of the tested crude extracts significantly enhanced their all-trans retinoic acid-induced differentiation. These activities were not associated with phthalate esters and/or PAHs. Our results indicate that cellular and biochemical in vitro assays based on various specific modes of action may yield data complementary to results of mutagenicity tests and that they could be useful in environmental risk assessment. High levels of PAHs are apparently associated with dioxin-like and mutagenic activities rather than with estrogenic activity.

Biological Assay↗

PubMed2001

Using the jackknife-based scoring method for measuring LRP onset effects in factorial designs.

Miller, Patterson, and Ulrich (1998) introduced a jackknife-based method for measuring the differences between two conditions in the onset latencies of the lateralized readiness potential (LRP). The present paper generalizes such jackknife-based methods to factorial experiments with any combination of within- and between subjects factors. Specifically, we introduce a subsample scoring method to assess potential main and interaction effects on LRP onsets within conventional yet slightly adjusted analyses of variance (ANOVAs) and post hoc comparison procedures.

Adult↗

PubMed2001

Brief bimanual force pulses: correlations between the hands in force and time.

Three experiments assessed coupling phenomena in the coordination of bimanual force pulses. Experiment 1 required symmetric force pulses (equal target forces and rise times for both hands) using the index finger of each hand. As the authors expected, on the basis of bimanual pointing movement results, this experiment revealed positive correlations between both the force rise times and the force amplitudes of the two hands. Experiments 2 and 3 included asymmetric conditions with different target force amplitudes (Experiment 2) or target rise times (Experiment 3). In Experiment 2 force amplitudes but not rise times were fully decoupled in the asymmetric condition. In the asymmetric condition of Experiment 3, however, neither rise times nor force amplitudes were fully decoupled. The results suggest a hierarchical control structure with temporal control dominating nontemporal control of bimanual force coordination.

Adult↗

PubMed2000

Puumala (PUU) hantavirus strain differences and insertion positions in the hepatitis B virus core antigen influence B-cell immunogenicity and protective potential of core-derived particles.

Hepatitis B virus (HBV) core-derived chimeric particles carrying a Puumala (PUU) hantavirus (strain Vranica/Hällnäs) nucleocapsid (N) protein sequence (aa 1-45), alternatively inserted at three distinct positions (N-, C-terminus, or the internal region), and mosaic particles consisting of HBV core as well as core/PUU (Vranica/Hällnäs) N (aa 1-45) readthrough protein were generated. Chimeric particles carrying the insert at the N-terminus or the internal region of core induced some protective immune response in bank voles (Clethrionomys glareolus) against a subsequent PUU virus (strain Kazan) challenge; 40-50% of the animals showed markers of protection. In contrast, internal insertion of PUU strain CG18-20 N (aa 1-45) into the HBV core caused a highly protective immune response in the bank vole model. Immunizations with particles carrying aa 75-119 of PUU (CG18-20) N at the C-terminus of core verified the presence of a second, minor protective region in the N protein. A strong PUU N-specific antibody response was detected not only in bank voles immunized with chimeric particles containing internal and N-terminal fusions of PUU N protein but also in animals immunized with the corresponding mosaic particles. Except for the exclusive occurrence of antibodies directed against aa 231-240 of N in non-protected animals post virus challenge, there was no additional obvious difference in the epitope-specificity of N-specific antibodies from immunized animals prior and post virus challenge.

Amino Acid Sequence↗

PubMed2000

Formation of immunogenic virus-like particles by inserting epitopes into surface-exposed regions of hamster polyomavirus major capsid protein.

We generated highly immunogenic virus-like particles that are based on the capsid protein VP1 of the hamster polyomavirus (HaPV-VP1) and harbor inserted foreign epitopes. The HaPV-VP1 regions spanning amino acids 81-88 (position 1), 222/223 (2), 244-246 (3), and 289-294 (4) were predicted to be surface exposed. An epitope of the pre-S1 region of the hepatitis B virus (designated S1; amino acid sequence DPAFR) was introduced into the predicted positions of VP1. All VP1/S1 fusion proteins were expressed in yeast and generated virus-like particles. Immunoassays using the S1-specific monoclonal antibody MA18/7 and immunization of C57Bl6 mice with different VP1/S1 constructs showed a pronounced reactivity and a strong S1-specific antibody response for particles carrying the insert in position 1, 2, 1+2, and 1+3. Our results suggest that HaPV-VP1 represents a highly flexible carrier moiety for the insertion of foreign sequences offering a broad range of potential uses, especially in vaccine development.

Amino Acid Sequence↗

PubMed2000

Mechanisms of speed-accuracy tradeoff: evidence from covert motor processes.

Speed-accuracy tradeoff (SAT) refers to the inverse relation between speed and accuracy found in many tasks. The present study employed reaction times (RTs) and movement-related brain potentials arising during the RT interval (lateralized readiness potentials; LRPs) to examine the mechanisms by which people control their position along an SAT continuum. Many models of SAT postulate that changes in position across conditions (macro-tradeoffs) and trial-by-trial variations within conditions (micro-tradeoffs) are mediated, at least in part, by the same mechanisms. These include: (1) all models that postulate mixtures of guesses and accurate responses and (2) some models postulating decision criterions applied to accumulating evidence or response tendencies. Such models would seem to be rejected for conditions under which macro- and micro-tradeoffs can be shown to involve no stages of RT in common. Under the present conditions, the two types of SAT produced additive effects on RT, with the macro-tradeoff involving only that portion of the RT interval occurring after LRP onset and the micro-tradeoff involving only that portion before LRP onset. These findings imply that the two types of SAT arose during different serial stages of RT and that the macro-tradeoff involved only stages occurring after differential preparation of the two hands had begun.

Brain↗

PubMed2000

Crohn's disease: a rare cause of upper airway obstruction.

Although uncommon, lesions of Crohn's disease can involve the hypopharynx and lower respiratory tract. We describe a patient with partial airway obstruction secondary to Crohn's disease of the hypopharynx and larynx. This entity should be considered in the differential diagnosis of patients presenting to the Emergency Department with upper airway obstruction.

Adult↗

PubMed2000

An immunodominant, cross-reactive B-cell epitope region is located at the C-terminal part of the hamster polyomavirus major capsid protein VP1.

The VP1 represents the major capsid protein of the hamster polyomavirus (HaPV). Here we describe the mapping of epitopes along the VP1 using Escherichia coli-expressed VP1-dihydrofolate reductase (DHFR) fusion proteins and PepScan analysis. By use of DHFR fusion proteins an immunodominant region was localized in the C-terminal part of VP1 between amino acids 320-384. Further epitopes are located in the regions amino acids 1-133 and amino acids 133-320, respectively. There were no obvious differences in the reactivity between sera of tumor-bearing and papilloma-free naturally HaPV-infected hamsters. In contrast, PepScan analysis revealed linear epitopes in the regions amino acids 79-97 and amino acids 353-367 for tumor-bearing animals and amino acids 101-113 and amino acids 165-179 for papilloma-free animals. The region between amino acids 320-384 of HaPV-VP1 was found to be involved in cross-reactivity of VP1 from HaPV and other polyomaviruses. Previously we have demonstrated that heterologous expression of HaPV-VP1 allowed the formation of virus-like particles (VLPs). From epitope mapping data and structural predictions it has been suggested that HaPV-VP1-VLPs may tolerate foreign peptides in the region amino acids 81-88 and the C-terminal part of VP1.

Amino Acid Sequence↗

PubMed2000

Impact of risperidone on seclusion and restraint at a state psychiatric hospital.

OBJECTIVE: To evaluate the impact of risperidone on seclusion and restraint in patients at a state psychiatric facility, shortly after risperidone's release. METHODS: Patients who were in the hospital for at least 3 months prior to receiving risperidone and subsequently received risperidone for at least 3 months formed the cohort. A mirror-image design was used with duration to a maximum of 1 year before and 1 year after initiation of risperidone. The hospital population that did not receive either risperidone or clozapine during the same time period was used for comparison of trends of seclusion and restraint. RESULTS: Seventy-four patients (most with schizophrenia) met the inclusion criteria of the risperidone group. There were statistically significant decreases in the number of seclusion hours (2.2 [SD 5.5] to 0.26 [SD 0.06]) and of events (0.23 [SD 0.59] to 0.05 [SD 0.14]) per person per month during risperidone treatment, compared with the prerisperidone treatment period (P = 0.01). The comparison group also evidenced decreases on these measures during the same time period, but the risperidone-treated cohort achieved a proportionally greater reduction. There were similar trends toward reduction in the restraint measures during risperidone treatment compared with prerisperidone, but these did not achieve statistical significance. The comparison group also showed slightly decreased use of restraints over the study period. CONCLUSIONS: Risperidone appears to have had a positive impact on seclusion in this state-hospital psychiatric population. These data support the positive impact of risperidone on violence found in other studies. Violence and aggression are major factors that affect morale among psychiatric patients and staff. So, any benefit in this regard as a result of antipsychotic drug treatment is salutary for patients, families, and health care providers.

Adult↗