Search PubMed⌕ Search

Biomedical subjects

R Nagel

Publications and source records attributed to R Nagel.

At least 19 recordsLinked to original sources

Bioconcentration, biomagnification and metabolism of 14C-terbutryn and 14C-benzo[a]pyrene in Gammarus fossarum and Asellus aquaticus.

The contribution of bioconcentration and biomagnification of 14C-terbutryn and 14C-benzo[a]pyrene via food and water to the bioaccumulation in Gammarus fossarum and Asellus aquaticus was investigated in single species-tests. In this investigation the uptake of 14C-terbutryn and 14C-benzo[a]pyrene via food and water by G. fossarum (L.) and A. aquaticus (L.) was examined. Bioconcentration factors (BCFs) and biomagnification factors (BMFs) were determined. Calculated BCFs were clearly higher than BMFs, indicating that water is the primary route of uptake. The uptake of terbutryn and benzo[a]pyren via water in G. fossarum and A. aquaticus is faster than uptake via food. The elimination and metabolism of the two chemicals by G. fossarum and A. aquaticus were studied. Terbutryn was eliminated almost completely in both species. In general, the elimination of terbutryn from G. fossarum and A. aquaticus was fast with half-life of 5 h. The elimination of terbutryn by G. fossarum after biomagnification is slower than after bioconcentration. No difference was found in elimination of terbutryn by A. aquaticus after biomagnification and after bioconcentration. Metabolites of terbutryn in G. fossarum and A. aquaticus were analyzed by HPLC. After the bioconcentration experiment a higher percentage of metabolites was found in G. fossarum than in A. aquaticus. This was confirmed for the experiment with uptake via food. The spectrum of metabolites was similar in both species, with hydroxyterbutryn being the major metabolism product in water. 14C-B[a]P could nearly completely be eliminated by G. fossarum (rest of activity 2%) after uptake via water. 14C-B[a]P could not be eliminated by G. fossarum and A. aquaticus after uptake via food. The metabolite could not be identified.

Amphipoda↗

Population structure and dynamics of Gammarus fossarum (Amphipoda) upstream and downstream from effluents of sewage treatment plants.

Two streams in Germany (Körsch and Lockwitzbach), each with two sampling sites above and below a sewage treatment plant (STP) discharging effluent, were investigated. Sampling sites were characterized, and exposure monitoring for chemicals with known or assumed endocrine disrupting potential was carried out. Both the population structure and the population dynamics of Gammarus fossarum were examined. The physicochemical parameters measured at the sampling sites of the Lockwitzbach and Körsch streams were found not to reach levels having an acute toxic impact on the development of gammarids. The calculated estrogenic potential in the stream water was 22- to 35-fold higher at the downstream site of the Körsch compared with the other sampling sites, mainly because of the concentrations of 17alpha-ethinylestradiol on two sampling dates. At both streams, an influence of the respective STP effluent on the sex ratio of G. fossarum was not observed. Moreover, intersexuality was not induced by these effluents. Differences in the structure and dynamics of G. fossarum populations were more pronounced at the Körsch than at the Lockwitzbach. At the downstream sampling site at the Körsch, gammarids reached their highest abundances. Particularly at the downstream sampling site of the Körsch, the proportion of breeding female gammarids and the proportion of juvenile gammarids in the smallest body length class were decreased compared with upstream. Adult gammarids were larger from the Lockwitzbach downstream site, but they were smaller from the Körsch downstream site compared with the respective upstream site. At the Körsch, the earlier onset of the autumnal reproductive resting period could be caused by the influence of the STP effluent.

Acanthocephala↗

Endocrine effects in Gammarus fossarum (Amphipoda): influence of wastewater effluents, temporal variability, and spatial aspects on natural populations.

In a field study, individuals of autochthounous populations of the amphipod Gammarus fossarum were examined for their maturity status, oocyte development, and biochemical parameters associated with their reproductive cycle. Variability in these parameters was related to abiotic exposure parameters varying in accordance to wastewater discharges, stream identity, and time. Patterns of all investigated parameters showed predominantly seasonal rather than spatial influence for both exposure and biologic effects. Single selected-effect parameters, however--such as the maturity index, late vitellogenic oocyte size and atresia, and the hsp90 level--responded to a sewage treatment plant discharge showing an estrogenic potential and also correlated significantly with the concentration of potential xenoestrogens at the different locations.

Amphipoda↗

Direct costs of microsurgical management of radiosurgically amenable intracranial pathology in Germany: an analysis of meningiomas, acoustic neuromas, metastases and arteriovenous malformations of less than 3 cm in diameter.

BACKGROUND: The purpose of the analysis was to appreciate and compare the effective direct costs of microsurgical treatment of intracranial pathology potentially amenable to radiosurgery as they arose in 1998-99. METHOD: Treatment costs of 127 microsurgically treated patients harbouring an arteriovenous malformation (AVM), acoustic nEuroma, meningioma or brain metastasis potentially amenable to radiosurgery were reviewed. Costs for the surgical procedure, ICU care, medical and nursing care on the ward, interclinical bills (ICB) for services provided by other departments and the overhead for basic hotel service were added. For comparison Gamma Knife costs were calculated by dividing the global operating cost of the Gamma Knife centre by the number of patients treated in 1999. FINDINGS: Average hospitalisation time for the entire microsurgical patients was 15,4+/-8,6 days. The patients spent an average of 1,2+/-2,8 days on ICU. Average operating time for all patients, including preparation, was 393+/-118 minutes. Average costs for the microsurgical therapy were Euro10.814+/-6.108. These consisted of Euro1417+/-426 for the surgical procedure, Euro1.188+/-2.658 for ICU care, Euro2.333+/-1.582 for medical and nursing care on the ward, Euro1.671+/-1.433 for interclinical bills and Euro 4.204+/-2.338 for basic hotel service (overhead, Euro273/day). 70% of the microsurgically treated patients needed ancillary inpatient rehabilitation or radiotherapy resulting in an average additional cost for all patients of Euro2.744. Furthermore 20% of the microsurgically treated patients required an unplanned readmission after discharge, resulting in an average additional costs for all patients of Euro1.684. Average overall costs per patient including ancillary therapy and unplanned readmissions amounted to Euro15.242. For comparison, Gamma Knife treatment costs per patient amounted to Euro7.920 in 1999. INTERPRETATION: The current analysis showed that for established radiosurgical indications the primary costs of microsurgery exceeded the costs of radiosurgery. Differences with regard to additional expenses as a consequence of disability were not addressed in this study. Microsurgical management as well as Gamma Knife radiosurgery have potential for economic improvement.

Brain Neoplasms↗

Release of U18 snoRNA from its host intron requires interaction of Nop1p with the Rnt1p endonuclease.

An external stem, essential for the release of small nucleolar RNAs (snoRNAs) from their pre-mRNAs, flanks the majority of yeast intron-encoded snoRNAs. Even if this stem is not a canonical Rnt1p substrate, several experiments have indicated that the Rnt1p endonuclease is required for snoRNA processing. To identify the factors necessary for processing of intron-encoded snoRNAs, we have raised in vitro extracts able to reproduce such activity. We found that snoRNP factors are associated with the snoRNA- coding region throughout all the processing steps, and that mutants unable to assemble snoRNPs have a processing-deficient phenotype. Specific depletion of Nop1p completely prevents U18 snoRNA synthesis, but does not affect processing of a dicistronic snoRNA-coding unit that has a canonical Rnt1p site. Correct cleavage of intron-encoded U18 and snR38 snoRNAs can be reproduced in vitro by incubating together purified Nop1p and Rnt1p. Pull-down experiments showed that the two proteins interact physically. These data indicate that cleavage of U18, snR38 and possibly other intron-encoded snoRNAs is a regulated process, since the stem is cleaved by the Rnt1p endonuclease only when snoRNP assembly has occurred.

DNA Primers↗

DNA ploidy is a valuable predictor for prognosis of patients with resected renal cell carcinoma.

BACKGROUND: Renal cell carcinomas (RCCs) are heterogeneous and include several distinct entities with a range of biologic and clinical behaviors from relatively favorable to extremely aggressive. The heterogeneity leads to unpredictable outcome and survival. DNA ploidy is a relatively new predictor differentiating diploid from aneuploid tumor cells according to regular or irregular DNA content. The authors evaluated the predictive value of DNA ploidy in patients who underwent resection because of RCC. METHODS: In a prospective study, 180 patients who underwent resection because of RCC were investigated. DNA cytometry was conducted on each resected tumor to determine DNA ploidy. Patients were completely followed up until death or up to 12 years. RESULTS: Survival analysis showed that patients who underwent resection because of RCC in tumor classifications pT1, pT2, and pT3 survived 10 years in 85%, 53%, and 8% of cases, respectively. Patients suffering from small tumors (pT1 and pT2, n = 44) with diploid nuclei survived 10 years in 94% but only in 8% if the tumor was aneuploid (n = 55). In addition, 91% of patients who underwent resection of large tumors (pT3, n = 12) with diploid nuclei survived 10 years, but no patient with large and aneuploid tumor (n = 51) survived more than 3 years. Furthermore, 92% of all patients afflicted from diploid RCC survived 10 years. This finding was independent of tumor stage. CONCLUSIONS: The results of this study suggest that DNA ploidy is a significant and independent predictor for survival of patients afflicted from RCC and superior to tumor classification and grade. DNA ploidy is a reliable prognostic factor for RCC and yields considerable information for patient management and predicting clinical outcome.

Adult↗

Artificial indoor streams as a method to investigate the impact of chemicals on lotic communities.

The potential hazard of chemicals on aquatic communities are generally evaluated by standardised single-species bioassays. Safety assessment is based on results gained from organisms adapted to lentic systems and biological interactions in ecosystems are neglected. While lotic communities are often at first in contact with chemicals, it is astonishing that microcosms with lentic communities are mainly used as a bridge between laboratory bioassays and outdoor aquatic systems. Hence, we established five artificial indoor streams to simulate abiotic factors of small rivers. The closed-circuit system was filled with nutrients added to tap water. Washed pebbles were used as sediment. The dynamics of a simple biocoenoses consisting of aufwuchs, Lumbriculus variegatus Asellus aquaticus and Gammarus fossarum was investigated. The dynamic of aufwuchs and periphyton was determined as dry weight and chlorophyll-a, respectively and qualitatively by pigment pattern. The abundance of different developmental stages of L. variegatus was determined at the end of the experiment as well as the population dynamics of G. fossarum and A. aquaticus. Survival rates of gammarids and juveniles per female were investigated and data were used for modelling the population dynamics. The experiment was carried out to investigate the performance of the established artificial streams and the developed approaches to investigate effects of chemicals on a basic lotic community. The prime reason to establish this approach was to close a gap between complex artificial stream systems and laboratory single species tests to assess the impact of chemicals on the aquatic environment.

Animals↗

Alkaline phosphatase activity: new assay for the Reflotron system. Results of the evaluation in eight clinical laboratories.

A new reagent carrier, Reflotron ALP, has been developed for the Reflotron system, allowing easy and rapid measurement (in less than 3 minutes) of alkaline phosphatase (ALP) activity in capillary blood, venous blood, heparinized plasma or serum. The evaluation of the analytical performance of the assay was carried out at eight clinical laboratories. The study of the imprecision using the measurements in human samples resulted in coefficients of variation ranging from 1.3% to 4.6% (within-run) and from 3.2% to 4.0% (day-to-day). The analytical specificity of the Reflotron ALP assay agrees well with ALP methods using a N-methyl-D-glucamine buffer solution. The calibration of the Reflotron ALP assay, however, is related to the reference intervals for ALP methods using a diethanolamine buffer solution. Method comparisons were performed with the ALP method on Hitachi instruments using diethanolamine buffer. Reflotron ALP measurements in blood and plasma in 157 randomly selected split samples showed excellent agreement (slope: 0.99; intercept: 0.7 U/l; median bias: 2.3%; median difference from the comparison method: -0.3%). Specimens from pregnant women and adolescents were excluded from this study. Differing values were obtained in a method comparison using 48 samples containing predominantly the ALP bone isoform (slope: 0.81; intercept: 31.5 U/l; median bias: 5.7%; median difference from the comparison method: -12.2%). Regression analysis of the results from 21 sera with prevailing placental ALP gave a slope of 1.51, and an intercept of -41.1 U/l (median bias: 8.6%; median difference from the comparison method: 35.6%). Reflotron ALP was compared with three different wet chemistry procedures using different buffer compounds: N-methyl-D-glucamine or diethanolamine or 2-amino-2-methyl-1-propanol. In samples containing predominantly ALP isoforms not of liver origin, the measurements with N-methyl-D-glucamine buffer gave the best fit with respect to Reflotron. In an interference study with 18 drugs, no effect on the test results could be detected. Total bilirubin up to 750 micromol/l and hemolysis up to 1.7 g/l free hemoglobin did not influence the test. Reflotron ALP proved to be an easy and rapid method with excellent precision. The accuracy related to an ALP method using diethanolamine buffer was good. The systematic differences for ALP in samples from pregnant women and adolescents have to be taken into account. The assay is well suited for differential diagnosis of hepatic diseases in decentralized testing.

Alkaline Phosphatase↗

Effects of terbutryn on aufwuchs and Lumbriculus variegatus in artificial indoor streams.

The effects of the herbicide terbutryn on a simple lotic food web were investigated during a 72-d exposure period in five artificial indoor streams in a greenhouse. The model compound terbutryn, an s-triazine and an inhibitor of photosynthesis, was applied once in each stream at nominal concentrations of 0.6, 6, 60, or 600 microg/L. Terbutryn concentrations in the water were analyzed by gas chromatography/mass spectrometry, and an overall time to 50% dissipation (DT50) of 28 d was calculated. The development of aufwuchs and the population growth and development of the oligochaete Lumbriculus variegatus were investigated. We determined that terbutryn was toxic to L. variegatus at 23.7 mg/L (96-h median lethal concentration [LC50]) and 16.5 mg/L (96-h median effective concentration [EC50]) in static acute toxicity tests. Terbutryn decreased aufwuchs production at 0.6 microg/L in the experimental streams. Population growth of L. variegatus was decreased by 50% at 6 microg/L. The effect of terbutryn on the aufwuchs was a direct effect of decreases in the periphyton. However, the effects on L. variegatus were an indirect effect of terbutryn as a consequence of decrease in the aufwuchs food source and occurred at three-orders-of-magnitude-lower concentrations of terbutryn than the acute toxicity effects. Our study demonstrates the utility of indoor lotic microcosm studies for evaluating both direct and indirect effects of contaminants on aquatic ecosystems.

Animals↗

[Animal transport in Europe--scope and trends].

In order to evaluate the importance of animal transports in the European Union, the figures on intra-Community trade, exports and imports can be used. In 1999, around 14.5 million animals (cattle, pigs, sheep, goats, horses) have been traded between Member States; the imports from third countries totalled 2.1 million heads and the exports to third countries 437.000 heads. The pattern of intra-Community trade is characterised by a clear trade flow from the Northern to the Southern Member Countries; the majority of the imports is coming from the Middle- and East European countries. Over the last few years, the annual volume of animal transports has been relatively stable, with the exception of cattle exports, where a significant reduction has taken place as from 1997.

Animals↗

Enhanced Tn10 and mini-Tn10 precise excision in DNA replication mutants of Escherichia coli K12.

The precise excision of transposon Tn10 and a mini-Tn10 derivative, inserted in the gal or lac operons, was studied in dnaB252 and dnaE486 temperature-sensitive mutants of Escherichia coli. dnaB codes for a DNA replication helicase and dnaE for the alpha subunit of DNA polymerase III. Mutations in these genes were found to enhance, at the permissive temperature, the precise excision of both genetic elements. The increase factor was much more pronounced for the dnaB252 mutant with the transposons inserted in gal. The stimulated excision was only partially affected by a recA null mutation but was significantly reduced by introduction of recF null or ruvA mutations. A model involving template switching of the polymerase between the direct repeats flanking the transposons, on the same strand or between sister strands, could account for the observed results.

Bacterial Proteins↗

Substrate recognition by a eukaryotic RNase III: the double-stranded RNA-binding domain of Rnt1p selectively binds RNA containing a 5'-AGNN-3' tetraloop.

Rnt1p is an RNase III homolog from budding yeast, required for processing snRNAs, snoRNAs, and rRNA. Numerous Rnt1p RNA substrates share potential to form a duplex structure with a terminal four-base loop with the sequence AGNN. Using a synthetic RNA modeled after the 25S rRNA 3' ETS cleavage site we find that the AGNN loop is an important determinant of substrate selectivity. When this loop sequence is altered, the rate of Rnt1p cleavage is reduced. The reduction in cleavage rate can be attributed to reduced binding of the mutant substrate as measured by a gel-shift assay. Deletion of the nonconserved N-terminal domain of Rnt1p does not affect cleavage site choice or the ability of the enzyme to distinguish substrates that contain the AGNN loop, indicating that this region is not required for selective cleavage. Strikingly, a recombinant fragment of Rnt1p containing little more than the dsRBD is able to discriminate between wild-type and mutant loop sequences in a binding assay. We propose that a major determinant of AGNN loop recognition by Rnt1p is present in its dsRBD.

Base Sequence↗

The sae locus of Staphylococcus aureus encodes a two-component regulatory system.

Sae is a regulatory locus that activates the production of several exoproteins in Staphylococcus aureus. A 3.4-kb fragment of a S. aureus genomic library, screened with a probe adjacent to the transposon insertion of a sae::Tn551 mutant, was cloned into a bifunctional vector. This fragment was shown to carry the sae locus by restoration of exoprotein production in sae mutants. The sae locus was mapped to the SmaI-D fragment of the staphylococcal chromosome by pulse-field electrophoresis. Sequence analysis of the cloned fragment revealed the presence of two genes, designated saeR and saeS, encoding a response regulator and a histidine protein kinase, respectively, with high homology to other bacterial two-component regulatory systems.

Amino Acid Sequence↗

RecBC and RecF recombination pathways and the induced precise excision of Tn10 in Escherichia coli.

Mitomycin C (MMC) treatment or mutations in uvrD enhance the frequency of Tn10 precise excision. We have shown previously that several repair-recombination genes, such as recA, ruv and recF are involved in the induced excision process. In this study, we find that other genes belonging to the RecBC and RecF sexual recombination pathways also participate in this process since mutations in recB, sbcB or recO diminish, though to different degrees, the frequency of Tn10 precise excision induced by MMC treatment or by uvrD mutants. Pairwise combinations of some of these mutations were also tested for Tn10 induced precise excision; most of these double mutants showed additive effects in reducing the frequency of the excision process. The results of these studies suggest that recombinational-repair genes, particularly recF, sbcB and recO have different roles in the induced excision of Tn10 than in recombinational mating.

Adenosine Triphosphatases↗

Application of the high risk model of threat perception to a primary care patient population.

This study was designed to test the hypothesis that patients with a tendency to somatize psychological distress into physical symptoms could be differentiated from patients who do not somatize on the basis of specific predisposing factors defined by the High Risk Model of Threat Perception. Patients in a family practice were assessed for the tendency to somatize by the Diagnostic Interview Schedule (DIS) and by physician rating. Twenty-seven percent of the patients were positive for tendency to somatize by physician rating. These patients had relatively high negative affect, absorption, catastrophizing, self-reported pain and stress, and greater utilization of services. None of the patients assessed by the DIS met criteria for somatization disorder, but 28% were positive for somatoform pain disorder. These patients also scored higher on the negative affect questionnaire, tended to have higher absorption scores, reported greater pain and stress, and utilized more services. Results of this study are partially supportive of the High Risk Model of Threat Perception, because two of the predisposer factors were associated both with tendency to somatize by physician rating and with somatoform pain disorder by interview. The higher utilization of services in the somatizing patients has cost and service ramifications. Treatment of patients with tendencies to somatize within a family practice setting are discussed.

Causality↗

Operation and diagnostic features of the VIP light.

Composite curing lights have been an equipment staple in the dental practitioner's office for many years. This article offers some insights into the design considerations of quartz-tungsten-halogen dental curing lights as well as the peripheral devices associated with these lights. Some of the features of the new Bisco VIP light are explained.

Calibration↗

Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers.

OBJECTIVE: To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. METHODS: Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity. RESULTS: MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP-1 was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity. CONCLUSION: Elevated MMP-3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity.

Arthritis↗