Biomedical subjects

A Preiss

Publications and source records attributed to A Preiss.

At least 19 recordsLinked to original sources

PubMed2006

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 3: Regeneration of bitumen fumes, inhalation setup, validation.

Undertaking a chronic inhalation study on bitumen fume presents a challenge in terms of generating sufficient amounts of representative fume. The objective of the study described in this and in previous publications was to collect sufficient fume and use this to develop a laboratory-generated exposure atmosphere, for use in chronic inhalation toxicity studies in rats that resembles, as closely as possible, personal exposures seen in workers during road paving operation. To achieve this goal, atmospheric workplace samples were collected at road paving work sites and compared with bitumen fume condensate samples collected from the headspace of hot bitumen storage tanks. In Parts 1 and 2, we described the collection and analysis of workplace samples, the strategy for in-line extraction of a suitable fraction of bitumen fume collected from the headspace of a bitumen storage tank and the comparison of the collected condensate to the workplace samples. This paper (Part 3) describes the regeneration of bitumen fume for inhalation and the exposure setup used for inhalation studies.

Aerosols↗

PubMed2006

Primary perineal hernia: a case report and review of the literature.

UNLABELLED: Pelvic floor hernias are extremely rare. This study presents a successfully treated case of primary perineal hernia and takes a look at the existing literature. CASE: The case of a 75-year-old female patient with a great perineal hernia is presented. Diagnosis was secured by magnetic resonance tomography. The pelvic defect was successfully treated by primary suture with Prolene. DISCUSSION: The literature shows many different approaches for treatment of perineal hernia, such as open or laparoscopic mesh repair, and perineal, abdominal or combined access. Our case confirms that primary closure of the hernial orifice through an abdominal approach is also feasible.

Aged↗

PubMed2006

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 2: Collection of bitumen fumes from storage tanks.

OBJECTIVES: The objective of the study described in this and an accompanying series of papers was to develop a laboratory generated exposure atmosphere to be used for chronic inhalation toxicity studies in rats that resembles, as closely as possible, personal exposures seen by workers during road paving operations. METHODS: To achieve this objective, atmospheric workplace samples were collected at road paving worksites and compared analytically with bitumen fume samples collected from the headspace of hot bitumen storage tanks. In Preiss et al. (2006) the collection and analysis of workplaces samples is described. This contribution describes the strategy for the in-line extraction of a suitable fraction of bitumen fume collected from the headspace of a bitumen storage tank and the comparison of the collected condensate to workplace samples. RESULTS: Results show that is possible to develop a collecting procedure that allows sampling from hot bitumen storage tanks in an operational asphalt mixing plant. The sampling procedure has been optimized to collect material that matches the workplace samples as closely as possible. The comparison to workplace samples has been performed using parameters that can be analyzed in both the workplace samples and the bitumen fume condensate collected from the tanks. Boiling point distribution (BPD), UV fluorescence (UV-Fl) and content of individual polycyclic aromatic hydrocarbons (PAH) were selected as parameters. The BPD of the final collected bitumen fume condensate did not differ by more than 17 degrees C from any point on the average BPD curve of the workplace samples, in the range from 5 to 95%. UV-Fl of the bitumen fume condensate nearly exactly matched the average UV-Fl of the workplace samples. However, the sum of the 17 PAHs analyzed in the test samples, compared to the mass of the condensate, is lower by a factor of approximately 3 than the sum of the 17 PAHs in some personal samples compared to the mass of Total Organic Matter (TOM). It has to be recognised that during the collection of the workplace samples, despite all efforts a number of the workers who carried a personal sampler could not be prevented from smoking.

Air Pollutants, Occupational↗

PubMed2006

Collection, validation and generation of bitumen fumes for inhalation studies in rats Part 1: Workplace samples and validation criteria.

OBJECTIVES: Undertaking a chronic inhalation study on bitumen fume presents a challenge in terms of generating large amounts of representative fume. The objective of the study described in this and the following contributions was to collect sufficient fume and develop a laboratory-generated exposure atmosphere that resembles, as closely as possible, personal exposures seen in workers during road paving operations, for use in chronic inhalation toxicity studies in rats. METHODS: To achieve this goal, atmospheric workplace samples were collected at road paving work sites both by Shell Global Solutions, Int. (Shell) and by the 'Berufsgenossenschaftliches Institut für Arbeitssicherheit' (BIA, Germany) and compared with bitumen fume condensate samples collected from the head space of hot bitumen storage tanks. Part 1 describes the collection and analysis of personal and static workplace samples. Different sampling methods were also used to allow a comparison of the standard German sampling method with the most common industry method used. Samples were analyzed by Shell, BIA and by the Fraunhofer Institute of Toxicology and Experimental Medicine (Fh-ITEM, Germany) using different methods. Parameters determined were: total particulate matter (TPM), benzene soluble matter (BSM), semi-volatiles (SV), total organic matter (TOM), boiling point distribution (BPD), polycyclic aromatic hydrocarbons (PAHs) and UV fluorescence (UVF). RESULTS: The BPD of personal and static samples had almost identical start and end points, but static samples show a tendency towards an increase in amounts of higher boiling point compounds. Personal samples generally show higher PAH concentrations than comparable static samples. The results of the analysis of personal workplace samples were used to establish validation/acceptance criteria for the bitumen fume condensate sampled from storage tanks for the inhalation study, which is described in a further publication. CONCLUSIONS: The criteria involve a range of parameters that can be analyzed in both workplace samples and samples of tank fume condensate: BPD, UVF and content of individual PAHs were selected as parameters.

Air Pollutants, Occupational↗

PubMed2003

Human biomonitoring of pyrethrum and pyrethroid insecticides used indoors: determination of the metabolites E-cis/trans-chrysanthemumdicarboxylic acid in human urine by gas chromatography-mass spectrometry with negative chemical ionization.

This work describes a gas chromatographic-mass spectrometric method employing negative chemical ionization (NCI) for the determination of E-cis/trans-chrysanthemumdicarboxylic acid (CDCA) in human urine used as a biomarker for the exposure to pyrethrum and/or certain pyrethroids in insecticide formulations applied indoors. Mixed-mode solid phase extraction was utilized for sample cleanup. Extraction recoveries ranged from 92 to 104% (2-9% R.S.D.). The acids were esterified with 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) allowing both their gas chromatographic separation and their sensitive mass spectrometric detection under NCI conditions. Detection limits of ca. 0.05 microg/l urine were achieved.

Calibration↗

PubMed2003

Verapamil: identification of novel metabolites in cultures of primary human hepatocytes and human urine by LC-MS(n) and LC-NMR.

1. Verapamil is a well-known and world-wide prescribed calcium antagonist, but it suffers from extensive first-pass metabolism. Although it has been marketed for many years, a complete understanding of its biotransformation in humans is still lacking. 2. The metabolism of verapamil was therefore investigated in cultures of primary human hepatocytes and in extracts of human urine after oral dosing. Identification of metabolites was done with LC-MS(n) and LC-NMR (600 MHz) to obtain in-depth information on its biotransformation products and definitive proof of the proposed chemical structures of metabolites. 3. Hyphenation of LC-MS(n) and LC-NMR was shown to be a powerful and effective platform for the identification of metabolites. Indeed, 21 Phase I and 16 Phase II metabolites were identified. Basically, all the Phase II metabolites (glucuronides) and 11 of the Phase I (oxidative) metabolites were not reported previously. 4. New insight into verapamil's biotransformation pathway is provided as well as evidence about its true complexity of metabolic disposal.

Biotransformation↗

PubMed2001

Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila.

Notch is the receptor for a conserved signaling pathway that regulates numerous cell fate decisions during development [1]. Signal transduction involves the presenilin-dependent intracellular processing of Notch and the nuclear translocation of the intracellular domain of Notch, NICD [2-6]. NICD associates with Suppressor of Hairless [Su(H)], a DNA binding protein, and Mastermind (Mam), a transcriptional coactivator [7-9]. In the absence of Notch signaling, Su(H) acts as a transcriptional repressor [10, 11]. Repression by Su(H) is relieved by the activation of Notch [12-16]. In the Drosophila embryo, this transcriptional switch from repression to activation is important for patterning the expression of the single-minded (sim) gene along the dorsoventral axis [12]. Here, we investigate the mechanisms by which Su(H) inhibits the expression of Notch target genes in Drosophila. We show that Hairless, an antagonist of Notch signaling [17-19], is required to repress the transcription of the sim gene. Hairless forms a DNA-bound complex with Su(H). Furthermore, it directly binds the Drosophila C-terminal Binding Protein (dCtBP), which acts as a transcriptional corepressor. The dCtBP binding motif of Hairless is essential for the function of Hairless in vivo. We propose that Hairless mediates transcriptional repression by Su(H) via the recruitment of dCtBP.

Alcohol Oxidoreductases↗

PubMed2001

Combination of matrix solid-phase dispersion extraction and direct on-line liquid chromatography-nuclear magnetic resonance spectroscopy-tandem mass spectrometry as a new efficient approach for the rapid screening of natural products: application to the total asterosaponin fraction of the starfish Asterias rubens.

A combination of matrix solid-phase dispersion extraction (MSPD) and LC-NMR-MS hyphenation is proposed as a rapid screening method of natural products for unknown compounds. In this report, this new analytical approach is applied for the first time. MSPD represents a significant simplification compared to classical extraction procedures and is thus an excellent complement to the fast and powerful LC-NMR-MS: MSPD yields extracts suitable for LC-NMR-MS in one simple preparation step, while LC-NMR-MS yields a wealth of information in one single chromatographic run. The suitability of this technique to characterise glycosidic compounds in the molecular mass range of 1200 to 1400 a.m.u. is demonstrated. The information on the number of exchangeable protons provided by an additional back-exchange experiment proved to be particularly valuable for structural elucidation. The possibility of semi-quantitative LC-NMR measurements through methyl signals H(3)-18 and 19 of the steroidal skeleton is demonstrated and is ensuingly used to provide relative quantitative data of the steroid oligosaccharide fraction.

Animals↗

PubMed2001

[Gene polymorphisms of hemostasis and coronary risk].

Hemostatic disorders are substantially involved in the pathogenesis of coronary heart disease and acute coronary syndromes. In addition to biochemical markers, gene polymorphisms of hemostasis have been intensively studied in terms of their association with coronary risk. These include polymorphisms of the genes of platelet glycoproteins, fibrinogen, prothrombin, factors V, VIII and XIII, plasminogen activator inhibitor-1 and tissue-type plasminogen activator. An association of a certain gene polymorphism with an increased coronary risk has usually been demonstrated in retrospective case-control studies. However, numerous clinical studies have not yet been able to identify any of these polymorphisms as unequivocal risk factors of coronary heart disease or acute coronary syndromes. These inconsistencies are mainly due to the complexity of the pathogenesis of coronary heart disease and the minor contribution of a single polymorphism to total coronary risk. This review reports on essential requirements of future studies as a prerequisite to improve our understanding of the genetic basis of coronary heart disease.

Blood Coagulation Factors↗

PubMed2001

Dynamic expression of Drosophila TRAF1 during embryogenesis and larval development.

TNF-receptor associated factors (TRAFs) comprise a family of adaptor proteins that act as downstream signal transducers of the TNF receptor superfamily and the Toll/interleukin-1 receptor family. The mammalian TRAFs 2, 5 and 6 are known to activate JNK- and NF-kappaB signaling pathways, whereas the function of the other three mammalian family members, TRAF 1, 3 and 4 is less well characterized. Vertebrate TRAFs have a very similar structure with the exception of TRAF1: aside the characteristic C-terminal TRAF domain, they share a N-terminal RING finger followed by five or, in the case of TRAF4, seven regularly spaced zinc fingers. Two TRAF homologues are present in the genome of Drosophila melanogaster, DTRAF1 and DTRAF2 (also known as DTRAF6) and both have been implicated in the Toll-receptor pathways leading to the activation of NF-kappa B and JNK. DTRAF1 is most closely related to mammalian TRAF4 which is predominantly expressed during nervous system development and in ephitelial progenitor cells. In order to gain insight into possible roles of DTRAF1 during development, we have performed a detailed transcriptional analysis of the gene at various embryonic and larval stages.

Animals↗

PubMed2001

Scalloped and strawberry notch are target genes of Notch signaling in the context of wing margin formation in Drosophila.

The Notch pathway regulates the differentiation of many cell types throughout development of higher metazoa. Different cellular responses are elicited through specific activation of distinct Notch target genes. In the Drosophila wing, for example, the cut gene is activated by Notch signaling along the dorso-ventral boundary but, as we show here, not in other cell types. We identify additional regulatory components, scalloped and strawberry notch, that are targets of the Notch pathway specifically within the wing anlagen. As suggested by physical interactions, these proteins could be co-factors of the cut trans-regulator Vestigial. Additional regulatory input comes from the Wingless pathway. Our data support a model, whereby context specific involvement of distinct co-regulators modulates Notch target gene activation.

Alleles↗

PubMed2001

Cross-fostering inhalation toxicity study with HCFC-123 in lactating Sprague-Dawley rats.

A study was performed in Sprague-Dawley rats (Crl:CD BR) to differentiate between effects of hydrofluorocarbon 123 (HCFC-123) on the lactating dam or on the fetus using fostering and cross-fostering of the offspring. Pregnant and/or lactating dams without the pups present were exposed to the test substance (1000 ppm) or clean air by whole-body inhalation for 6 h/day from day 6 to 19 post conceptionem (p.c.) and from day 5 to 21 post partum (p.p.). Pups were cross-fostered to new dams within the first 2 days after birth. Treatment of the mothers with HCFC-123 led to decreases in serum glucose, cholesterol, and triglycerides and increases in absolute and relative maternal liver weights. Decreased litter and individual pup weight and decreased serum triglycerides were observed in the pups of treated foster mothers. Treatment of the mothers with HCFC-123 did not influence milk production based on the body weight difference of the dam before suckling and 60 min after beginning of suckling using 12-pup "standard litters" of untreated dams. Total fat, glucose, and protein contents in the milk were also not influenced by the treatment. Trifluoroacetic acid (TFA), a main metabolite of HCFC-123, was observed in urine samples of standard litters that had been nursed by treated dams. In conclusion, the effects on offspring due to HCFC-123 treatment consisted of decreased pup weight and decreased serum triglycerides at weaning. All effects were due to treatment of the lactating dams, as no prenatally induced effects were found. Since milk production and nutritional constituents of the milk were not influenced, but significant amounts of the main metabolite were found in pup urine, an effect of HCFC-123 or its metabolite on the pups via maternal milk is considered to be a possible cause for their decreased weight gain.

Administration, Inhalation↗

PubMed2000

Characterization of dyes and other pollutants in the effluent of a textile company by LC/NMR and LC/MS

LC/NMR and LC/MS (the latter technique in the MSn mode) were used to characterize the organic constituents of industrial wastewater with emphasis on polar, nonvolatile compounds. In the effluent of a textile company, various compounds such as anthraquinone-type dyes and their byproducts, a fluorescent brightener, a byproduct from polyester production, and auxiliaries such as anionic and nonionic surfactants and their degradation products were identified. It is shown that the combined use of both hyphenated techniques provides complementary structural information. If applied under comparable chromatographic conditions, they are well-suited for the nontarget analysis.

Journal Article↗

PubMed2000

Su(H)-independent activity of hairless during mechano-sensory organ formation in Drosophila.

Formation of mechano-sensory organs in Drosophila involves the selection of neural precursor cells (SOPs) mediated by the classical Notch pathway in the process of lateral inhibition. Here we show that the subsequent cell type specifications rely on distinct subsets of Notch signaling components. Whereas E(spl) bHLH genes implement SOP selection, they are not required for later decisions. Most remarkably, the Notch signal transducer Su(H) is essential to determine outer but not inner cell fates. In contrast, the Notch antagonist Hairless, thought to act upon Su(H), influences strongly the entire cell lineage demonstrating that it functions through targets other than Su(H) within the inner lineage. Thereby, Hairless and numb may have partly redundant activities. This suggests that Notch-dependent binary cell fate specifications involve different sets of mediators depending on the cell type considered.

Animals↗

PubMed2000

Neural hyperplasia induced by RNA interference with m4/malpha gene activity.

The E(spl) complex (E(spl)-C) contains three different classes of genes that are downstream of Notch signaling. The bHLH genes mediate the Notch signal by repressing proneural gene activity, for example during the singularization of mechanosensory organ precursor cells (SOPs). Genes of the second class, the E(spl) m4/malpha family, antagonize this process if overexpressed. Here we show that this is based on dominant-negative effects since RNA interference gives neurogenic phenotypes indistinguishable from E(spl)-C mutations. Furthermore, a third member of the m4/malpha gene family, named bbu/tom, behaves differently with respect to RNA expression patterns, its regulation by Notch signaling and loss of function phenotypes.

Animals↗

PubMed2000

Measurement of antithrombin activity by thrombin-based and by factor Xa-based chromogenic substrate assays.

Functionally active antithrombin can be quantified by chromogenic substrate assays utilizing the heparin cofactor activity of antithrombin and the inhibition rates of thrombin or of activated factor X (FXa). Thrombin-based assays but not FXa-based assays may overestimate the antithrombin activity due to their sensitivity toward heparin cofactor II. We focused on the question whether an overestimation of antithrombin activity by thrombin-based assays involves the risk of misdiagnosing antithrombin-deficient individuals as being non-deficient. We determined antithrombin using two thrombin-based assays and one FXa-based assay in 27 plasma samples from patients with acquired antithrombin deficiency spiked with lepirudin, in antithrombin-deficient plasma and in mixtures of antithrombin-deficient plasma and normal plasma. We also measured antithrombin in healthy subjects, in patients with inherited and acquired antithrombin deficiency and in patients under high-dose heparin treatment. At therapeutic final concentrations of lepirudin, antithrombin activities were considerably overestimated by the thrombin-based assays but not by the FXa-based assay. The residual antithrombin activities in antithrombin-deficient plasma determined by the thrombin-based assays were markedly higher than the corresponding values obtained with the FXa-based assay. The thrombin-based assays also overestimated antithrombin activity in patients under high-dose heparin. However, the degree of overestimation in the range between 50 and 100 IU/dl was too low to misidentify individuals with inherited or acquired antithrombin deficiency as normal. We conclude that functionally active antithrombin can be reliably determined using FXa-based chromogenic substrate assays in all settings examined. Thrombin-based assays must not be used in patients under treatment with hirudin or other direct thrombin inhibitors.

Adult↗

PubMed1999

Notchspl is deficient for inductive processes in the eye, and E(spl)D enhances split by interfering with proneural activity.

Eye development in Drosophila involves the Notch signaling pathway at several consecutive steps. At first, Notch signaling is required for stable expression of the proneural gene atonal (ato), thereby maintaining neural potential of the cells. Second, in a process of lateral inhibition, Notch signaling is necessary to confine neural commitment to individual photoreceptor founder cells. Later on, the successive addition of cells to maturing ommatidia is under Notch control. In contrast to previous assumptions, the recessive Notch allele split (Nspl) involves specifically loss of the early proneural Notch activity in the eye, which is in agreement with bristle defects as well. As a result, fewer cells gain neural potential and fewer ommatidia are founded. Enhancement of this phenotype by the dominant mutation Enhancer of split [E(spl)D] happens within the remaining proneural cells, in which Ato expression is abolished. In line with genetic data, this process occurs primarily at the protein level due to altered protein-protein interactions between the aberrant E(spl)D and proneural proteins. Nspl is the first Notch mutation known to specifically affect Notch inductive processes during eye development.

Alleles↗

PubMed1999

Comparative studies of the leachate of an industrial landfill by gas chromatography-mass spectrometry, liquid chromatography-nuclear magnetic resonance and liquid chromatography-mass spectrometry.

Nowadays, the need to have a realistic characterization of industrial effluents in the environment has become more and more recognized. A palette of different analytical methods both for sample extraction and instrumental analysis are available today, some older, others introduced more recently. The aim of this research is to compare a number of these techniques. To do this we studied a real leachate from an industrial landfill and carried out chemical analyses for organic pollutants, using different extraction methods based on solid-phase extraction and solid-phase microextraction and different instrumental techniques such as GC-MS, LC-MS, NMR and LC-NMR. Results show the performances of the different techniques, which are complementary.

Chromatography, Liquid↗