65 results on '"Hallier A"'
Search Results
2. Application des méthodes géophysiques pour le diagnostic de l’aléa cavités sur des ouvrages de grands linéaires, en contexte ferroviaire et hydraulique
- Author
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Christophe Vergniault, Edouard Buchoud, Joséphine Boisson-Gaboriau, and Amélie Hallier
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General Medicine - Abstract
Cet article traduit la volonté de deux maîtres d’ouvrages (ayant une compétence interne d’ingénierie conseils en géophysique), que sont SNCF Réseau et EDF, de mettre en commun leurs retours d’expériences pour améliorer la gestion des risques liés à l’aléa cavités souterraines sur des ouvrages de grands linéaires, en contexte ferroviaire ou hydraulique. Cette coopération a permis de valider plusieurs méthodes de diagnostic, par reconnaissance et auscultation, afin de détecter des cavités souterraines et de suivre leur évolution : dans deux contextes géologiques distincts (craie et marnes à gypse), les méthodes sismiques actives et passives basées sur les ondes de surface ont confirmé leurs performances théoriques, aussi bien pour des reconnaissances que de la surveillance en continu : (1) dans un contexte de cavités anthropiques dans la craie et hors nappe, les exemples présentés valident l’intérêt de certaines méthodes industrielles de reconnaissance (DCOS®, ParSeis®) et laissent espérer une industrialisation prochaine de plusieurs autres (SI active et passive), (2) dans le contexte de dissolution de gypse, ces mêmes méthodes utilisant le signal généré par les circulations ferroviaires se sont avérées très pertinentes pour assurer une surveillance en continu, via un monitoring 4D, du sol support de la plateforme ferroviaire. Le résultat de ce développement permettra de s’inscrire dans une démarche de maintenance prédictive vis-à-vis du risque fontis ; dans le contexte de dissolution de gypse, la mesure de déformation par fibre optique en place dans un remblai a démontré sa pertinence pour capter l’amorce de remontée d’un fontis, avant même l’apparition d’indice en surface. Enfin, il faut noter que les méthodes de reconnaissance et d’auscultation, présentées dans les deux premiers cas d’étude, pourraient favorablement être réalisées en utilisant une fibre optique comme celle exploitée dans le troisième cas d’étude, mais il faudrait un interrogateur optique différent de type DAS. Ceci est une perspective à laquelle s’intéressent les deux maîtres d’ouvrages.
- Published
- 2022
3. Large eddy simulation in a rotary blood pump: Viscous shear stress computation and comparison with unsteady Reynolds-averaged Navier–Stokes simulation
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Matthias Witte, Lucas Konnigk, Frank-Hendrik Wurm, Benjamin Torner, Sebastian Hallier, and Jitendra Kumar
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Computation ,0206 medical engineering ,Flow (psychology) ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,030204 cardiovascular system & hematology ,Computational fluid dynamics ,Physics::Fluid Dynamics ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,Viscous shear stress ,Humans ,Computer Simulation ,Physics ,business.industry ,Models, Cardiovascular ,General Medicine ,Mechanics ,020601 biomedical engineering ,Blood pump ,Blood damage ,Hydrodynamics ,Heart-Assist Devices ,Stress, Mechanical ,Reynolds-averaged Navier–Stokes equations ,business ,Large eddy simulation - Abstract
Purpose: Numerical flow analysis (computational fluid dynamics) in combination with the prediction of blood damage is an important procedure to investigate the hemocompatibility of a blood pump, since blood trauma due to shear stresses remains a problem in these devices. Today, the numerical damage prediction is conducted using unsteady Reynolds-averaged Navier–Stokes simulations. Investigations with large eddy simulations are rarely being performed for blood pumps. Hence, the aim of the study is to examine the viscous shear stresses of a large eddy simulation in a blood pump and compare the results with an unsteady Reynolds-averaged Navier–Stokes simulation. Methods: The simulations were carried out at two operation points of a blood pump. The flow was simulated on a 100M element mesh for the large eddy simulation and a 20M element mesh for the unsteady Reynolds-averaged Navier-Stokes simulation. As a first step, the large eddy simulation was verified by analyzing internal dissipative losses within the pump. Then, the pump characteristics and mean and turbulent viscous shear stresses were compared between the two simulation methods. Results: The verification showed that the large eddy simulation is able to reproduce the significant portion of dissipative losses, which is a global indication that the equivalent viscous shear stresses are adequately resolved. The comparison with the unsteady Reynolds-averaged Navier–Stokes simulation revealed that the hydraulic parameters were in agreement, but differences for the shear stresses were found. Conclusion: The results show the potential of the large eddy simulation as a high-quality comparative case to check the suitability of a chosen Reynolds-averaged Navier–Stokes setup and turbulence model. Furthermore, the results lead to suggest that large eddy simulations are superior to unsteady Reynolds-averaged Navier–Stokes simulations when instantaneous stresses are applied for the blood damage prediction.
- Published
- 2018
4. Combusting vegetable oils in diesel engines: the impact of unsaturated fatty acids on particle emissions and mutagenic effects of the exhaust
- Author
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J. Bünger, Jürgen Bünger, Olaf Jens Schröder, Thomas Brüning, Axel Munack, Jürgen Krahl, Götz A. Westphal, and Ernst Hallier
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Salmonella typhimurium ,0301 basic medicine ,food.ingredient ,Health, Toxicology and Mutagenesis ,010501 environmental sciences ,Toxicology ,Diesel engine ,01 natural sciences ,03 medical and health sciences ,Diesel fuel ,food ,Linseed oil ,Plant Oils ,Organic chemistry ,Food science ,Gasoline ,Vehicle Emissions ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,Mutagenicity Tests ,Chemistry ,Coconut oil ,General Medicine ,030104 developmental biology ,Vegetable oil ,Biofuel ,Biofuels ,Fatty Acids, Unsaturated ,Particulate Matter ,Mutagens ,Polyunsaturated fatty acid - Abstract
High particle emissions and strong mutagenic effects were observed after combustion of vegetable oil in diesel engines. This study tested the hypothesis that these results are affected by the amount of unsaturated or polyunsaturated fatty acids of vegetable oils. Four different vegetable oils (coconut oil, CO; linseed oil, LO; palm tree oil, PO; and rapeseed oil, RO) and common diesel fuel (DF) were combusted in a heavy-duty diesel engine. The exhausts were investigated for particle emissions and mutagenic effects in direct comparison with emissions of DF. The engine was operated using the European Stationary Cycle. Particle masses were measured gravimetrically while mutagenicity was determined using the bacterial reverse mutation assay with tester strains TA98 and TA100. Combustion of LO caused the largest amount of total particulate matter (TPM). In comparison with DF, it particularly raised the soluble organic fraction (SOF). RO presented second highest TPM and SOF, followed by CO and PO, which were scarcely above DF. RO revealed the highest number of mutations of the vegetable oils closely followed by LO. PO was less mutagenic, but still induced stronger effects than DF. While TPM and SOF were strongly correlated with the content of polyunsaturated fatty acids in the vegetable oils, mutagenicity had a significant correlation with the amount of total unsaturated fatty acids. This study supports the hypothesis that numbers of double bounds in unsaturated fatty acids of vegetable oils combusted in diesel engines influence the amount of emitted particles and the mutagenicity of the exhaust. Further investigations have to elucidate the causal relationship.
- Published
- 2015
5. Monitoring of myocutaneous flaps by intracapillary glucose and lactate measurements : experimental study
- Author
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Guillier David, Moris Vivien, Cristofari Sarra, Gerenton Brice, Hallier Anna, Rizzi Philippe, Zwetyenga Narcisse, Service Chirurgie Maxillo-Faciale - Stomatologie - Chirurgie Plastique Réparatrice et Esthétique - Chirurgie de la main (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de chirurgie plastique et reconstructive [Hôpital Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe NuTox (LNC - U1231) (NUTOX), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Saint Louis [APHP], Equipe NuTox (LNC - U1231) ( NUTOX ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), and Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM )
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Salvage therapy ,experimentation ,Medicine ,Pharmacology (medical) ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,glucose ,Ligature ,[ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,thrombosis ,lactate ,business.industry ,General Medicine ,Gold standard (test) ,microsurgery ,Microsurgery ,medicine.disease ,Thrombosis ,3. Good health ,Surgery ,monitoring ,medicine.anatomical_structure ,Ligation ,business ,Complication ,Artery - Abstract
IF 2.4; International audience; Introduction: In surgery, some defects require reconstruction with microsurgical flap. The free flap failure rate varies between 2% and 5% with severe. Vascular thrombosis is the most frequent complication and represents 15-73%. The success rate of salvage therapy is greater when salvage surgery is early. Currently clinical monitoring is the gold standard. Many non-invasive or minimally invasive techniques have been developed to improve early diagnosis of complications of vascular thrombosis. Each technique has advantages and disadvantages. The aim of our experimental study was to compare the clinical assessment and intracapillary glycemia and lactataemia measurements during monitoring of free flaps. Material and methods: Pigs (Sus scrofa domesticus) were operated under general anesthesia. A myocutaneous latissimus dorsi with skin paddle was performed. Each animal was operated twice (right and left) similarly. 4 groups were made: Group 1 (no flap ligature or control group); Group 2 (flap with final ligation of the artery); Group 3 (flap with final ligation of the two veins); Group 4 (flap with transient ligature of the artery and two veins for 1 hour). An incision was made in the center of the skin paddle to make the measurements. Postoperative monitoring protocol consisted of a triple monitoring: clinical, biological and histological. Results: Eight animals were operated and sixteen flaps were realized. Each flap was clinically and biologically tested 25 times. Clinical, biological and histological monitoring showed significant variations according to the groups. Discussion-Conclusion: Experimentally the intra-capillary measures of lactate and glucose levels associated with clinical monitoring may shorten the delay in diagnosis. Ultimately this will save lives and achieve better functional and aesthetic results.
- Published
- 2017
6. Detection of T-Wave Beat-By-Beat Variations prior to Ventricular Arrhythmias Onset in ICD-Stored Intracardiac Electrograms: The Endocardial T-Wave Alternans Study (ETWAS)
- Author
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Jean-Luc Pasquié, Pierre Winum, Benoit Hallier, Chao Lin, Philippe Maury, Jérôme Taieb, Lionel Beck, Corinne Mailhes, Anne Rollin, Frank Raczka, Alexandre Duparc, Francis Castanie, Philippe Rolland, Jean-Yves Tourneret, and Pierre Mondoly
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Fibrillation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,General Medicine ,T wave alternans ,030204 cardiovascular system & hematology ,Ventricular tachycardia ,medicine.disease ,Implantable cardioverter-defibrillator ,Sudden death ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,cardiovascular system ,Cardiology ,Medicine ,Repolarization ,030212 general & internal medicine ,Electrical conduction system of the heart ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Brugada syndrome - Abstract
The aim of the Endocardial T-Wave Alternans Study was to prospectively assess the presence of T-wave alternans (TWA) or beat-to-beat repolarization changes on implantable cardioverter-defibrillator (ICD)-stored electrograms (EGMs) immediately preceding the onset of spontaneous ventricular tachycardia (VT) or fibrillation (VF).
- Published
- 2014
7. Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides
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Ronja Schiemann, Jürgen J. Heinisch, Eva Cordes, Anders Malmendal, Stefan Walter, Jessica Vitos-Faleato, Heiko Meyer, Benjamin Hallier, and Achim Paululat
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0301 basic medicine ,QH301-705.5 ,Science ,medicine.medical_treatment ,insulin expression ,feeding behavior ,metallopeptidase ,Peptide ,General Biochemistry, Genetics and Molecular Biology ,neprilysin ,03 medical and health sciences ,0302 clinical medicine ,peptide metabolism ,medicine ,Biology (General) ,insulin signaling ,Neprilysin ,chemistry.chemical_classification ,Peptide Metabolism ,D. melanogaster ,General Immunology and Microbiology ,biology ,General Neuroscience ,Insulin ,fungi ,General Medicine ,Phenotype ,Insulin receptor ,Developmental Biology and Stem Cells ,Epidemiology and Global Health ,030104 developmental biology ,chemistry ,Biochemistry ,biology.protein ,Medicine ,Ectopic expression ,Signal transduction ,030217 neurology & neurosurgery ,Research Article - Abstract
Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition. Ectopic expression of a catalytically inactive mutant did not elicit any of the phenotypes, which confirms abnormal peptide hydrolysis as a causative factor. A screen for corresponding substrates of the neprilysin identified distinct peptides that regulate insulin-like peptide expression, feeding behavior, or both. The high functional conservation of neprilysins and their substrates renders the characterized principles applicable to numerous species, including higher eukaryotes and humans. DOI: http://dx.doi.org/10.7554/eLife.19430.001, eLife digest The hormone insulin and similar molecules called insulin-like peptides act as signals to control many processes in the body, including growth, stress responses and aging. Disrupting these signaling pathways can cause many diseases, with diabetes being the most common of these. Although the roles of the signaling pathways have been well studied, it is less clear how the body controls the production of insulin and insulin-like peptides. Neprilysins are enzymes that can cut other proteins and peptides by a process known as hydrolysis. Their targets (known as “substrates”) include peptides that regulate a range of cell processes, and neprilysins have therefore been linked with many diseases. Fruit flies have at least five different neprilysin enzymes, but their substrates have not yet been identified. One of these, known as Nep4A, is produced in muscle tissue and appears to be important for muscles to work properly. Hallier, Schiemann et al. reveal that Nep4A regulates the production of insulin-like peptides. The experiments used fruit fly larvae that had been genetically engineered so that the level of Nep4A could be altered in muscle tissue. Larvae with very high or very low levels of Nep4A eat less food, have smaller bodies and produce different amounts of insulin-like peptides compared to normal larvae. Further experiments show that Nep4A can hydrolyze a number of peptides that regulate the production and the release of insulin-like peptides. This suggests that the enzymatic activity of neprilysins plays a direct role in controlling the production of insulin. The next challenge is to find out whether these findings apply to humans and other animals that also have neprilysins. DOI: http://dx.doi.org/10.7554/eLife.19430.002
- Published
- 2016
8. Effects of sampling and extraction on deoxynivalenol quantification
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Arnaud Hallier, Florian Celette, and Christophe David
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Grinding process ,Detection limit ,Wheat grain ,Extraction (chemistry) ,Sampling (statistics) ,General Medicine ,Analytical Chemistry ,Agitator ,chemistry.chemical_compound ,chemistry ,Environmental science ,Limit (mathematics) ,Biological system ,Mycotoxin ,Food Science - Abstract
Deoxynivalenol was extracted from wheat grain and quantified by GC-ECD. The quantification of deoxynivalenol can be critical, for example in certifying the amount of the mycotoxin in a lot and determining if this amount is over or under a fixed limit. Thus, an objective was to obtain representative samples to monitor DON quantification variability. We show that among the different steps of analysis the critical one is grain sampling. We also show that we were able to significantly improve the extraction rate without increasing the variability by using a longer extraction time with a magnetic agitator, and a grinding process which takes into account both the heterogeneous repartition of deoxynivalenol within wheat grains and different extraction rates according to the size of the flour powder particles. Thus, it could be of interest to use this methodology to determine if a lot is above or below a maximum limit because it enables the detection limit to be lowered, thereby simplifying the subsequent analysis.
- Published
- 2011
9. Usefulness of real-time PCR as a complementary tool to the monitoring of Legionella spp. and Legionella pneumophila by culture in industrial cooling systems
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A. Touron-Bodilis, C. Pougnard, H. Frenkiel-Lebossé, and S. Hallier-Soulier
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Biocide ,biology ,Legionella ,General Medicine ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Legionella pneumophila ,Management tool ,respiratory tract diseases ,Microbiology ,Real-time polymerase chain reaction ,Colony count ,Food science ,Biotechnology - Abstract
Aims: This study was designed to evaluate the usefulness of quantification by real-time PCR as a management tool to monitor concentrations of Legionella spp. and Legionella pneumophila in industrial cooling systems and its ability to anticipate culture trends by the French standard method (AFNOR T90-431). Methods and Results: Quantifications of Legionella bacteria were achieved by both methods on samples from nine cooling systems with different water qualities. Proportion of positive samples for L. pneumophila quantified by PCR was clearly lower in deionized or river waters submitted to a biocide treatment than in raw river waters, while positive samples for Legionella spp. were quantified for almost all the samples. For some samples containing PCR inhibitors, high quantification limits (up to 4·80 × 105 GU l−1) did not allow us to quantify L. pneumophila, when they were quantified by culture. Finally, the monitoring of concentrations of L. pneumophila by both methods showed similar trends for 57–100% of the samples. Conclusions: These results suggest that, if some methodological steps designed to reduce inhibitory problems and thus decrease the quantification limits, could be developed to quantify Legionella in complex waters, the real-time PCR could be a valuable complementary tool to monitor the evolution of L. pneumophila concentrations. Significance and Impact of the Study: This study shows the possibility of using real-time PCR to monitor L. pneumophila proliferations in cooling systems and the importance to adapt nucleic acid extraction and purification protocols to raw waters.
- Published
- 2011
10. Investigation of the association of Apgar score with maternal socio-economic and biological factors: an analysis of German perinatal statistics
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Gerhard Jorch, Sebastian Straube, Volker Briese, Ulrike Borchardt, Ernst Hallier, and Manfred Voigt
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Medicine & Public Health ,Human Genetics ,Endocrinology ,Obstetrics/Perinatology ,Gynecology ,Overweight ,Body Mass Index ,German ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Germany ,Obstetrics and Gynaecology ,030212 general & internal medicine ,reproductive and urinary physiology ,2. Zero hunger ,Smoking ,Obstetrics and Gynecology ,General Medicine ,female genital diseases and pregnancy complications ,3. Good health ,Parity ,language ,population characteristics ,Female ,Apgar score ,medicine.symptom ,Live birth ,Live Birth ,Maternal Age ,Women, Working ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,Mothers ,Social class ,Young Adult ,03 medical and health sciences ,Body mass index ,Maternal age ,Socio-economic factors ,030225 pediatrics ,medicine ,Humans ,business.industry ,Infant, Newborn ,Materno-Fetal Medicine ,medicine.disease ,Infant newborn ,language.human_language ,Social Class ,Apgar Score ,business ,Demography - Abstract
PURPOSE: To examine the relationship of 5-min Apgar score with maternal socio-economic and biological factors. METHODS: We analyzed data from 465,964 singleton pregnancies (37–41 weeks’ gestation) from the German perinatal statistics of 1998–2000. Using a logistic regression model we analyzed the incidence of low (0–6) 5-min Apgar scores in relation to these maternal factors: body mass index (BMI), age, previous live births, country of origin, occupation, single mother status, working during pregnancy, and smoking. RESULTS: A low Apgar score was more common in overweight [adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10–1.40; P < 0.001] and obese [OR 1.92 (95% CI 1.67–2.20); P < 0.001] compared to normal weight women. A low Apgar score was also more common for women aged >35 years compared to those aged 20–35 years [OR 1.35 (95% CI 1.16–1.58); P < 0.001]. Furthermore, odds of a low Apgar score were higher for women with no previous live births compared to those with one or more previous live births [OR 1.52 (95% CI 1.37–1.70); P < 0.001]. Socio-economic factors did not convincingly influence Apgar scores. CONCLUSIONS: There was an influence of the biological maternal factors age, BMI, and parity on the 5-min Apgar score. There was no convincing effect of socio-economic factors on Apgar score in our study population. Possible reasons for this are discussed.
- Published
- 2009
11. The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations
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Ernst Hallier, Dirk Taeger, Angelika Mönnich, Nadine Lichey, Götz A. Westphal, and Jürgen Bünger
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Adult ,Male ,Cell Survival ,Cytochalasin B ,Metabolite ,Benzene ,para-Benzoquinone ,Phorbol-12-acetate-13-myristate ,Health, Toxicology and Mutagenesis ,Genotoxicity and Carcinogenicity ,medicine.disease_cause ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Benzoquinones ,Humans ,Phytohemagglutinins ,Carcinogen ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Micronucleus Tests ,biology ,Hydroquinone ,Dose-Response Relationship, Drug ,Mutagenicity Tests ,General Medicine ,Middle Aged ,Molecular biology ,Benzoquinone ,3. Good health ,chemistry ,Biochemistry ,13. Climate action ,030220 oncology & carcinogenesis ,Myeloperoxidase ,Micronucleus test ,Phorbol ,biology.protein ,Leukocytes, Mononuclear ,Tetradecanoylphorbol Acetate ,Female ,Genotoxicity ,Cell Division - Abstract
Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identiWed. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13- myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20–28 ng/ml PMA caused a signiWcant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 g/ml (0.37– 1.85 M). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene. peerReviewed
- Published
- 2009
12. Strong mutagenic effects of diesel engine emissions using vegetable oil as fuel
- Author
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Olaf Jens Schröder, Axel Munack, Birgit Emmert, Ernst Hallier, Yvonne Ruschel, Jürgen Bünger, Thomas Brüning, Jürgen Krahl, Götz A. Westphal, and Michael Müller
- Subjects
Salmonella typhimurium ,Fossil Fuels ,Biodiesel ,Rapeseed ,Mutagenicity Tests ,Chemistry ,Health, Toxicology and Mutagenesis ,Exhaust gas ,Esters ,General Medicine ,Fuel oil ,Toxicology ,Pulp and paper industry ,Diesel engine ,Fatty Acids, Monounsaturated ,Diesel fuel ,Vegetable oil ,Synthetic fuel ,Plant Oils ,Rapeseed Oil ,Gasoline ,Mutagens ,Vehicle Emissions - Abstract
Diesel engine emissions (DEE) are classified as probably carcinogenic to humans. In recent years every effort was made to reduce DEE and their content of carcinogenic and mutagenic polycyclic aromatic compounds. Since 1995 we observed an appreciable reduction of mutagenicity of DEE driven by reformulated or newly designed fuels in several studies. Recently, the use of rapeseed oil as fuel for diesel engines is rapidly growing among German transportation businesses and agriculture due to economic reasons. We compared the mutagenic effects of DEE from two different batches of rapeseed oil (RSO) with rapeseed methyl ester (RME, biodiesel), natural gas derived synthetic fuel (gas-to-liquid, GTL), and a reference diesel fuel (DF). The test engine was a heavy-duty truck diesel running the European Stationary Cycle. Particulate matter from the exhaust was sampled onto PTFE-coated glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The gas phase constituents were sampled as condensates. The mutagenicity of the particle extracts and the condensates was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Compared to DF the two RSO qualities significantly increased the mutagenic effects of the particle extracts by factors of 9.7 up to 59 in tester strain TA98 and of 5.4 up to 22.3 in tester strain TA100, respectively. The condensates of the RSO fuels caused an up to factor 13.5 stronger mutagenicity than the reference fuel. RME extracts had a moderate but significant higher mutagenic response in assays of TA98 with metabolic activation and TA100 without metabolic activation. GTL samples did not differ significantly from DF. In conclusion, the strong increase of mutagenicity using RSO as diesel fuel compared to the reference DF and other fuels causes deep concern on future usage of this biologic resource as a replacement of established diesel fuels.
- Published
- 2007
13. Influence of rearing conditions and feed on the biochemical composition of fillets of the European catfish (Silurus glanis)
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Carole Prost, Thierry Serot, and Arnaud Hallier
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chemistry.chemical_classification ,fungi ,Fatty acid ,General Medicine ,Biology ,biology.organism_classification ,Analytical Chemistry ,chemistry ,Biochemistry ,Freshwater fish ,Biochemical composition ,Dry matter ,Food science ,Silurus ,Fillet (mechanics) ,Chemical composition ,Food Science ,Catfish - Abstract
The biochemical composition of European catfish (Silurus glanis) fillets reared under two conditions used in France was studied. The biochemical composition of the two feeds used was also analysed, in order to establish a relationship between European catfish fillet composition and feed. Dry matter, protein, lipid and carbohydrate contents were determined. The fatty acid profile was determined by GC-FID and GC/MS. This work has established that European catfish has a biochemical composition characteristic of semi-fat fish, that the protein content is affected by water temperature, and that the lipid content depends largely on feed. This work has also highlighted that the proportions of fatty acids can be affected by rearing conditions, by feed, or by both rearing conditions and feed with a significant interaction between these two factors.
- Published
- 2007
14. Ärztliche Meldepflicht bei begründetem Verdacht auf Vorliegen einer Berufskrankheit
- Author
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B. Emmert and E. Hallier
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Health care ,medicine ,Occupational disease ,General Medicine ,medicine.disease ,business - Published
- 2006
15. New gas chromatography–olfactometric investigative method, and its application to cooked Silurus glanis (European catfish) odor characterization
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Philippe Courcoux, Arnaud Hallier, Thierry Serot, and Carole Prost
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chemistry.chemical_classification ,Chromatography ,biology ,musculoskeletal, neural, and ocular physiology ,Organic Chemistry ,Organoleptic ,General Medicine ,biology.organism_classification ,Biochemistry ,Analytical Chemistry ,law.invention ,Odor ,chemistry ,law ,Olfactometry ,Odorants ,Animals ,Flame ionization detector ,Volatile organic compound ,Gas chromatography ,Silurus ,Catfishes ,psychological phenomena and processes ,Catfish - Abstract
A new gas chromatography-olfactometric method, gas chromatography-global olfactometry omission detection (GC-GOOD), was applied to dynamic headspace odor extracts of Silurus glanis (European catfish). The GC-GOOD method is based on the omission test theory and uses a gas chromatograph coupled with a three-way valve and an a flame ionization detector. The GC-GOOD method enabled the identification of key families of volatile compounds in the S. glanis global odor and the elucidation of the interactions occurring between these families. Significant main effects were observed for the families of volatile compounds exhibiting cooked odor, grassy odor and alcohol, solvent and plastic odors. Omission of these families involved a loss of odor similarity.
- Published
- 2004
16. Genotoxic effects of N -nitrosodicyclohexylamine in isolated human lymphocytes
- Author
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Jürgen Bünger, Claudia Herting, Götz A. Westphal, Ernst Hallier, and Michael Müller
- Subjects
Salmonella typhimurium ,Nitrosamines ,Cytochalasin B ,Health, Toxicology and Mutagenesis ,Dicyclohexylamine ,Cell Count ,Mutagen ,Toxicology ,medicine.disease_cause ,Gas Chromatography-Mass Spectrometry ,Ames test ,chemistry.chemical_compound ,medicine ,Humans ,Diethylnitrosamine ,Lymphocytes ,Nitrite ,Cells, Cultured ,Micronucleus Tests ,Chromatography ,Dose-Response Relationship, Drug ,Cell Cycle ,N-Nitrosopyrrolidine ,General Medicine ,In vitro ,3. Good health ,chemistry ,Nitrosamine ,Environmental chemistry ,Micronucleus test ,Microsomes, Liver ,Cell Division ,Genotoxicity ,Mutagens - Abstract
Dicyclohexylamine x nitrite is classified as an "experimental equivocal tumorigenic agent" by the National Toxicology Program. Since no genotoxic effects of the substance itself are known, the reported tumorigenic potential of dicyclohexylamine x nitrite could be due to generation of N-nitrosodicyclohexylamine (N-NO-DCHA), which occurs under conditions of use and can be detected in foils that contain dicyclohexylamine x nitrite. Therefore, we investigated possible mutagenic properties of N-NO-DCHA in the Ames test and the cytokinesis-block micronucleus assay with human lymphocytes. Since N-NO-DCHA is not commercially available, the substance was synthesized and purified by thin-layer chromatography. Identity was confirmed by gas chromatography/mass spectroscopy (GC/MS) and 1H- and 13C-NMR. More than 97% purity was achieved. Stability and availability in the solvent were checked by GC/MS. N-NO-DCHA induced micronuclei in isolated human lymphocytes at a dose range of 15-100 micrograms/ml (= 71.4-476.2 microM), exceeding the base rate significantly at one or two nontoxic concentrations in four out of six experiments. For the Ames test, arochlor-1254-, beta-naphthoflavone/phenobarbital- and pyrazole-induced S9-fractions were used with Salmonella typhimurium TA100, TA1535, TA98 and TA104. No effects were seen in the Ames test, with the exception of microcolony induction at doses higher than 250 micrograms (= 1.2 mmol) N-NO-DCHA/plate using TA104 and 20% arochlor-1254 induced S9 at pH 6.5. In conclusion, N-NO-DCHA was negative in the Ames test using TA98, TA100 and TA1535, inconclusive using TA104, and weakly genotoxic in the in vitro micronucleus test with isolated human lymphocytes. With regard to the tumorigenicity of the majority of nitrosamines, our data underline the necessity of further studies on possible genotoxic effects of N-NO-DCHA.
- Published
- 2001
17. A contribution to reduce sampling variability in the evaluation of deoxynivalenol contamination of organic wheat grain
- Author
-
Florian Celette, Arnaud Hallier, Christophe David, and Julie Coutarel
- Subjects
Fusarium ,Food Handling ,Health, Toxicology and Mutagenesis ,Sample (material) ,Food Contamination ,Toxicology ,chemistry.chemical_compound ,Head blight ,Mycotoxin ,Triticum ,Wheat grain ,biology ,Public Health, Environmental and Occupational Health ,Sampling (statistics) ,Reproducibility of Results ,Water ,General Chemistry ,General Medicine ,Contamination ,biology.organism_classification ,Food Inspection ,Teratogens ,Agronomy ,chemistry ,Seeds ,Organic farming ,Environmental science ,Food, Organic ,France ,Trichothecenes ,Immunosuppressive Agents ,Food Science - Abstract
Fusarium head blight caused by different varieties of Fusarium species is one of the major serious worldwide diseases found in wheat production. It is therefore important to be able to quantify the deoxynivalenol concentration in wheat. Unfortunately, in mycotoxin quantification, due to the uneven distribution of mycotoxins within the initial lot, it is difficult, or even impossible, to obtain a truly representative analytical sample. In previous work we showed that the sampling step most responsible for variability was grain sampling. In this paper, it is more particularly the step scaling down from a laboratory sample of some kilograms to an analytical sample of a few grams that is investigated. The naturally contaminated wheat lot was obtained from an organic field located in the southeast of France (Rhône-Alpes) from the year 2008-2009 cropping season. The deoxynivalenol level was found to be 50.6 ± 2.3 ng g⁻¹. Deoxynivalenol was extracted with a acetonitrile-water mix and quantified by gas chromatography-electron capture detection (GC-ECD). Three different grain sampling techniques were tested to obtain analytical samples: a technique based on manually homogenisation and division, a second technique based on the use of a rotating shaker and a third on the use of compressed air. Both the rotating shaker and the compressed air techniques enabled a homogeneous laboratory sample to be obtained, from which representative analytical samples could be taken. Moreover, the techniques did away with many repetitions and grinding. This study, therefore, contributes to sampling variability reduction in the evaluation of deoxynivalenol contamination of organic wheat grain, and then, at a reasonable cost.
- Published
- 2013
18. Cytotoxic and mutagenic effects, particle size and concentration analysis of diesel engine emissions using biodiesel and petrol diesel as fuel
- Author
-
Olaf Jens Schröder, Peter Ruhnau, Thomas Schulz, K. Baum, Jürgen Bünger, Jürgen Krahl, Ernst Hallier, Götz A. Westphal, and Michael Müller
- Subjects
020209 energy ,Health, Toxicology and Mutagenesis ,02 engineering and technology ,010501 environmental sciences ,Toxicology ,medicine.disease_cause ,Diesel engine ,complex mixtures ,01 natural sciences ,7. Clean energy ,Cell Line ,Mice ,Diesel fuel ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Animals ,Particle Size ,Gasoline ,Vehicle Emissions ,0105 earth and related environmental sciences ,Biodiesel ,Chemistry ,Exhaust gas ,General Medicine ,Particulates ,Soot ,13. Climate action ,Biofuel ,Environmental chemistry ,Mutagens - Abstract
Diesel engine exhaust particles (DEP) contribute substantially to ambient air pollution. They cause acute and chronic adverse health effects in humans. Biodiesel (rapeseed oil methyl ester. RME) is used as a "green fuel" in several countries. For a preliminary assessment of environmental and health effects of RME, the particulate-associated emissions from the DEP of RME and common fossil diesel fuel (DF) and their in vitro cytotoxic and mutagenic effects were compared. A test tractor was fuelled with RME and DF and driven in a European standard test cycle (ECE R49) on an engine dynamometer. Particle numbers and size distributions of the exhausts were determined at the load modes "idling" and "rated power". Filter-sampled particles were extracted and their cytotoxic properties tested using the neutral red assay. Mutagenicity was tested using the Salmonella typhimurium/microsome assay. Despite higher total particle emissions, solid particulate matter (soot) in the emissions from RME was lower than in the emissions from DF. While the size distributions and the numbers of emitted particles at "rated power" were nearly identical for the two fuels, at "idling" DF emitted substantially higher numbers of smaller particles than RME. The RME extracts caused fourfold stronger toxic effects on mouse fibroblasts at "idling" but not at "rated power" than DF extracts. The extracts at both load modes were significantly mutagenic in TA98 and TA100. However, extracts of DF showed a fourfold higher mutagenic effect in TA98 (and twofold in TA100) than extracts of RME. These results indicate benefits as well as disadvantages for humans and the environment from the use of RME as a fuel for tractors. The lower mutagenic potency of DEP from RME compared to DEP from DF is probably due to lower emissions of polycyclic aromatic compounds. The higher toxicity is probably caused by carbonyl compounds and unburned fuel, and reduces the benefits of the lower emissions of solid particulate matter and mutagens from RME.
- Published
- 2000
19. Psychological effects upon exposure to polyhalogenated dibenzodioxins and dibenzofurans
- Author
-
Klaus Golka, Hansjoerg Kieper, Meinolf Blaszkewicz, Hermann M. Bolt, Ricarda Thier, B. Sietmann, Ernst Hallier, Ernst Kiesswetter, and Andreas Seeber
- Subjects
Adult ,Male ,Polychlorinated Dibenzodioxins ,Environmental Engineering ,Health, Toxicology and Mutagenesis ,Polychlorinated dibenzodioxins ,Industrial Waste ,chemistry.chemical_compound ,Halogens ,Animal science ,Occupational Exposure ,Humans ,Environmental Chemistry ,Trait anxiety ,Benzofurans ,Flame Retardants ,Mental Disorders ,Public Health, Environmental and Occupational Health ,Routine laboratory ,Mental disease ,General Medicine ,General Chemistry ,Dibenzofurans, Polychlorinated ,Middle Aged ,Pollution ,chemistry ,Environmental chemistry ,Combustion products ,Female ,Polychlorinated Dibenzodioxin ,Occupational exposure - Abstract
Thirty workers who had been exposed to combustion products for several years due to testing of flame retarding qualities of building materials and 30 controls from the same facility were investigated. Concentrations found in samples taken from different places of the facility were up to 14,660 μg/kg for polybrominated dibenzofurans and up to 67.1 μg/kg for polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). Physical examination, routine laboratory parameters, and blood fat concentrations of PCDDs and PCDFs revealed normal findings. Neurotoxic symptoms showed a weak tendency of overrepresentation among the exposed workers. The frequency of neurobehavioural symptoms increased significantly with trait anxiety independent of exposure to combustion products.
- Published
- 2000
20. Conjugal transfer of a TOL-like plasmid and extension of the catabolic potential ofPseudomonas putidaF1
- Author
-
V. Ducrocq, N. Truffaut, and S. Hallier-Soulier
- Subjects
biology ,Strain (chemistry) ,Immunology ,Genetic transfer ,General Medicine ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Microbiology ,Pseudomonas putida ,Plasmid ,Pseudomonadales ,Genetics ,bacteria ,Molecular Biology ,Soil microbiology ,Bacteria ,Pseudomonadaceae - Abstract
Strain mX was isolated from a petrol-contaminated soil, after enrichment on minimal medium with 0.5% (v/v) meta-xylene as a sole carbon source. The strain was tentatively characterized as Pseudomonas putida and harboured a large plasmid (pMX) containing xyl genes involved in toluene or meta-xylene degradation pathways via an alkyl monooxygenase and a catechol 2,3-dioxygenase. This new TOL-like plasmid was stable over two hundred generations and was self-transferable. After conjugal transfer to P. putida F1, which possesses the Tod chromosomal toluene biodegradative pathway, the transconjugant P. putida F1(pMX) was able to grow on benzene, toluene, meta-xylene, para-xylene, and ethylbenzene compounds as the sole carbon sources. Catechol 2,3-dioxygenases of the transconjugant cells presented a more relaxed substrate specificity than those of parental cells (strain mX and P. putida F1).Key words: biodegradation, conjugative transfer, toluene, xylene, Pseudomonas.
- Published
- 1999
21. Photometric determination of human serum bromide levels—a convenient biomonitoring parameter for methyl bromide exposure
- Author
-
Peter Reinhold, Marc L. Zeise, Ernst Hallier, Michael Müller, Martina Lange, and Uwe Jürgens
- Subjects
Bromides ,Male ,chemistry.chemical_element ,Toxicology ,01 natural sciences ,Photometry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Blood serum ,Bromide ,Occupational Exposure ,Biomonitoring ,medicine ,Humans ,Bromine ,Chromatography ,010401 analytical chemistry ,General Medicine ,Pesticide ,030210 environmental & occupational health ,Hydrocarbons, Brominated ,3. Good health ,0104 chemical sciences ,chemistry ,Environmental chemistry ,Toxicity ,Female ,Halothane ,Environmental Monitoring ,Methyl iodide ,medicine.drug - Abstract
Methyl bromide is one of the most important pesticides for the control of insects, fungi and nematodes. Serum bromide has been proposed as a biomonitor for occupational exposure to methyl bromide. Therefore, a novel, sensitive photometric method was developed for the determination of serum bromide at concentrations relevant for such exposure. Further possible applications are monitoring of intoxication victims and halothane narcosis. Using the method we have established a mean serum bromide level of 4.13±S.D. 1.05 mg/l (n/64) in a group of healthy female and male volunteers not knowingly exposed to bromide or bromine containing organics. Serum of a subject accidently exposed to methyl bromide revealed a bromide level of 11.5 mg/l serum, while two individuals exposed to methyl iodide had no elevated levels. A group of 30 agricultural workers showed a mean serum bromide level of 15.33±S.D. 1.90 mg/l at the end of the methyl bromide application season.
- Published
- 1999
22. Conjugal transfer of a TOL-like plasmid and extension of the catabolic potential of Pseudomonas putida F1
- Author
-
S. Hallier-Soulier, V. Ducrocq, and N. Truffaut
- Subjects
Immunology ,Genetics ,General Medicine ,Molecular Biology ,Applied Microbiology and Biotechnology ,Microbiology - Published
- 1999
23. Purification and characterization of a new glutathioneS-transferase, class δ, from human erythrocytes
- Author
-
Andreas Müller, Klaus R. Schröder, Frederike A. Wiebel, David J. Meyer, Hermann M. Bolt, and E. Hallier
- Subjects
Gene isoform ,chemistry.chemical_classification ,Erythrocytes ,Health, Toxicology and Mutagenesis ,Kinetics ,General Medicine ,Biology ,Toxicology ,Isozyme ,Enzyme assay ,Substrate Specificity ,Red blood cell ,Enzyme ,medicine.anatomical_structure ,chemistry ,Biochemistry ,medicine ,biology.protein ,Humans ,Antibody ,Gene ,Glutathione Transferase - Abstract
A new polymorphic form of glutathione S-transferase (GST), metabolising monohalogenated methanes, ethylene oxide and dichloromethane, has been purified from human erythrocytes and characterized. Several characteristics, such as similar elution patterns on different chromatographic matrices, KM-values and activity towards antibodies, confirm a previous assumption that this novel GST is a class theta enzyme. Although the presence or absence of the enzyme activity in human red blood cells is parallel with the polymorphism of the human GST T1 gene, the new GST theta in red blood cells may differ from the known GST T1-1 enzyme from other tissues in terms of substrate specificity, since established GST T1-1 substrates [1,2-epoxy-3-(p-nitro-phenoxy)propane and p-nitro-benzyl chloride] are not metabolized. The substrate specificity of the new enzyme in erythrocytes resembles more closely that of GST T2-2, most likely due to a common N-terminal modification which modifies substrate binding. The new polymorphic GST-isoform in human red blood cells therefore may be considered to represent an N-terminally modified isoform of GST T1-1.
- Published
- 1996
24. A note on individual differences in the urinary excretion of optical enantiomers of styrene metabolities and of styrene-derived mercapturic acids in humans
- Author
-
H. Karels, E. Hallier, Klaus Golka, and Hans Werner Goergens
- Subjects
Male ,Chromatography ,Chemistry ,Elution ,Health, Toxicology and Mutagenesis ,Individuality ,General Medicine ,Metabolism ,Urine ,Toxicology ,Mandelic acid ,Thin-layer chromatography ,Acetylcysteine ,Styrene ,Excretion ,chemistry.chemical_compound ,Occupational Exposure ,Epoxy Compounds ,Humans ,Mandelic Acids ,Chromatography, Thin Layer ,Enantiomer - Abstract
Urine samples from 20 male workers in the polyester industry exposed by inhalation to styrene concentrations ranging from 29 to 41 ppm were investigated. Excretion products of styrene metabolism, mandelic acid and mercapturic acids, were purified from the urine over an extraction column packed with Porapak Q, with subsequent ether elution. The optical enantiomers R- and S-mandelic acid were then determined by thin layer chromatography (TLC) using chiral plate material and selective staining with vanadium pentoxide. Quantitative analysis of these compounds was performed using commercial reference substances. Styrene-specific mercapturic acids were analyzed by a modified TLC method, using synthesized reference substances. The concentration of racemic mandelic acid in the individual urine samples ranged from 80 to 1610 mg/l, and the ratio of the R- and S-enantiomers ranged from 0.7 to 2.2. These individual variations are not explained by differences in individual styrene exposure levels, or by differences in the concentration of the urine samples (in relation to creatinine excretion). Styrene-specific mercapturic acids were detected in the urine of only 1 of the 20 workers, at a concentration much lower than expected from previous investigations by others in humans and laboratory animals, in which less specific analytical methods had been used. The results point to marked interindividual differences in metabolism of styrene, probably related to enzyme polymorphisms.
- Published
- 1995
25. Metabolism of dichloromethane (methylene chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase Theta (GST T1-1)
- Author
-
Beate Aust, Karin Asmuth, Anja Dommermuth, E. Hallier, Hans Werner Goergens, and Klaus R. Schröder
- Subjects
Erythrocytes ,Health, Toxicology and Mutagenesis ,Population ,Formaldehyde ,Toxicology ,Chloride ,chemistry.chemical_compound ,Bromide ,medicine ,Humans ,education ,Glutathione Transferase ,Dichloromethane ,Methylene Chloride ,education.field_of_study ,Polymorphism, Genetic ,Chromatography ,biology ,General Medicine ,Metabolism ,Enzyme assay ,Isoenzymes ,chemistry ,Biochemistry ,biology.protein ,medicine.drug ,Methyl iodide - Abstract
Human hemolysate was incubated in vitro with different concentrations of dichloromethane (methylene chloride). The resulting enzymatically mediated production of formaldehyde was determined by two independent analytical methods (Nash-reaction/colorimetry or HPLC). The formation of formaldehyde from dichloromethane is influenced by the polymorphism of glutathione-S-transferase (GST) Theta, in the same way as the metabolism of methyl bromide, methyl chloride, methyl iodide and ethylene oxide. Three quarters of the population (“conjugators”) possess, whereas one quarter (“non-conjugators”) lack this enzyme activity in human erythrocytes. The metabolism of dichloromethane in hemolysate in vitro can be described by Michaelis-Menten kinetics; for an individual with high GST T1-1 enzyme activity, the maximum velocity of formaldehyde production was calculated to be approximately 180 pmol/min per mg Hb, the k M being approximately 60 mM dichloromethane. Carcinogenicity of dichloromethane in long-term inhalation exposure of rodents has been attributed to metabolism of the compound via the GST-dependent pathway. Extrapolation of the results to humans for risk assessment should consider the newly discovered polymorphic enzyme activity of GST Theta. Furthermore, the possible existence of a “high-risk” population among humans should be considered in epidemiological research.
- Published
- 1994
26. A multiparametric PCR-based tool for fast detection and identification of spore-forming bacteria in food
- Author
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Sophie Jan, Danièle Sohier, Sylvie Hallier-Soulier, Florence Baron, Sonia Pavan, Michel Gautier, Florence Postollec, Anne Gabrielle Mathot, Stéphane Bonilla, Association pour le Développement de la Recherche Appliquée aux Industries Agricoles et Alimentaires, Pall GeneSystems, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Université de Brest (UBO), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
- Subjects
100 milliliters ,Food spoilage ,ADN ,Bacillus ,CLOSTRIDIUM ,BACTERIE ,Polymerase Chain Reaction ,ALIMENT ,Limit of Detection ,Spore germination ,raw-milk ,real-time pcr ,SPECIFICITY ,2. Zero hunger ,Spores, Bacterial ,0303 health sciences ,Food poisoning ,biology ,General Medicine ,Raw milk ,Bacterial Typing Techniques ,PCR ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Cereus ,[SDV.IDA.SMA]Life Sciences [q-bio]/Food engineering/domain_sdv.ida.sma ,DNA, Bacterial ,BACILLUS ,Food Contamination ,sp-nov ,Microbiology ,VALIDATION ,SPOILAGE ,DETECTION ,clostridium-tyrobutyricum spores ,strains ,03 medical and health sciences ,FOOD ,medicine ,Food microbiology ,gen-nov ,030304 developmental biology ,Bacteria ,IDENTIFICATION ,030306 microbiology ,business.industry ,bacillus-cereus group ,rdna ,biology.organism_classification ,medicine.disease ,DNA extraction ,Spore-forming ,Biotechnology ,Food Microbiology ,proposal ,business ,Food Science ,Food contaminant - Abstract
The presence of psychrotrophic or highly thermoresistant spore-forming bacteria in food and feedstuff responsible for food poisoning and spoilage raises major safety and economical issues. The aim of this study was to evaluate the performances of a ready-to-use PCR assay (alternative method) in comparison with the standard microbiological plating method regarding spore-forming bacteria detection in food samples. An overnight sample enrichment was selected to increase sporeformer diversity recovery, spore germination, bacterial growth and favour DNA extraction. A total of 180 sporeformer isolates representing 38 different species and 8 genera were tested in the PCR assays. Inclusivity and exclusivity results ensured specific detection and identification of the majority of targeted genera and species. Validation studies carried on artificially contaminated food samples showed detection of the inoculated contaminants in most cases, with increased detection limit for the alternative method which enabled detection with up 1 spore of B. cereus in 25 g food sample. Using naturally contaminated food samples, standard method comforted the alternative method. In a number of cases, the alternative method was able to identify species not detected with the standard method. In addition, identification and discrimination between the B. cereus group members was possible. Thus, associated to a key element, i.e., the enrichment step, the developed multiparametric PCR-based assays reported in this study provide a fast, sensitive and reliable detection and identification tool for mostly encountered spore-forming food contaminants. (C) 2010 Elsevier B.V. All rights reserved.
- Published
- 2010
27. New strategy for alerting central nervous system toxicity: Integration of blood-brain barrier toxicity and permeability in neurotoxicity assessment
- Author
-
Heidi Diallo, Pilar Prieto, Hanna Tähti, C. Landry, Dorothée Hallier-Vanuxeem, Maxime Culot, Roméo Cecchelli, Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), and Institució Catalana de Recerca i Estudis Avançats (ICREA)
- Subjects
Cell Membrane Permeability ,Cell Survival ,Central nervous system ,Tetrazolium Salts ,Pharmacology ,Biology ,Animal Testing Alternatives ,Toxicology ,Blood–brain barrier ,Nervous System ,Xenobiotics ,Neuroblastoma ,03 medical and health sciences ,0302 clinical medicine ,In vitro model ,Predictive Value of Tests ,Cell Line, Tumor ,medicine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,030304 developmental biology ,Blood-brain barrier ,Neurons ,0303 health sciences ,Neurotoxicity ,Reproducibility of Results ,Neurotoxicity assessment ,General Medicine ,medicine.disease ,In vitro ,3. Good health ,Thiazoles ,medicine.anatomical_structure ,Target site ,nervous system ,Cell culture ,Permeability (electromagnetism) ,Toxicity ,cardiovascular system ,Cattle ,Testing strategy ,030217 neurology & neurosurgery - Abstract
International audience; The combination of an in vitro BBB model (4d/24w) with a neuronal cell line (SH-SY5Y) provides a convenient approach to explore the importance of BBB permeability in neurotoxicity assessment of compounds. The toxicity of 16 compounds on SH-SY5Y cells was evaluated after 24 h incubation with each compound and compared to their toxicity on SH-SY5Y after passage through the BBB model. Nine out of 16 compounds were found toxic after direct exposure at 100 μM while only three still induced toxicity on SH-SY5Y cells after BBB transport. The BBB permeability values of each compound revealed that in the case of compounds that did not induce toxicity, the amount that crossed the BBB was not enough to exert a toxic effect on the neuronal cells. Since disrupting the BBB may also cause unwanted effect on brain cells, the BBB toxicity of these compounds have been assessed. Our results prompted the importance of BBB permeability assessment in neurotoxicity evaluation, as it allows a better estimation of the actual concentration at the target site.
- Published
- 2009
28. DNA binding of methyl iodide in male and female F344 rats
- Author
-
Daigen Xu, Ernst Hallier, H. Peter, B. Gansewendt, Hermann M. Bolt, and Ulrich Foest
- Subjects
Male ,Cancer Research ,Guanine ,Administration, Oral ,Mutagen ,Biology ,medicine.disease_cause ,chemistry.chemical_compound ,Oral administration ,Administration, Inhalation ,medicine ,Animals ,Potency ,Carbon Radioisotopes ,Hydrocarbons, Iodinated ,Lung ,Chromatography, High Pressure Liquid ,Carcinogen ,Adenine ,Hydrolysis ,Stomach ,DNA ,General Medicine ,Molecular biology ,Rats, Inbred F344 ,Rats ,stomatognathic diseases ,medicine.anatomical_structure ,Liver ,chemistry ,Biochemistry ,Gastric Mucosa ,Purines ,Toxicity ,Female ,Methyl iodide - Abstract
The genotoxic potency of methyl iodide was investigated in a DNA binding study. Male and female F344 rats were exposed to 14C-labelled methyl iodide orally or by inhalation in a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach of the exposed animals. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine could be identified by a combination of three different methods of hydrolysing DNA and subsequent HPLC or GC/MS analysis. The highest values of methylated guanines were determined in the stomach and forestomach of the animals following both oral and inhalative exposure. These results demonstrate a systemic genotoxic effect of methyl iodide.
- Published
- 1991
29. Formation of DNA adducts in F-344 rats after oral administration or inhalation of [14C]methyl bromide
- Author
-
H. Peter, H. M. Bolt, Xu Dg, B. Gansewendt, E. Hallier, and U. Foest
- Subjects
Male ,Guanine ,Stereochemistry ,Administration, Oral ,Pharmacology ,Toxicology ,High-performance liquid chromatography ,Gas Chromatography-Mass Spectrometry ,chemistry.chemical_compound ,Sex Factors ,Bromide ,Oral administration ,Administration, Inhalation ,medicine ,Animals ,Carbon Radioisotopes ,Lung ,Chromatography, High Pressure Liquid ,Carcinogen ,Inhalation exposure ,Inhalation ,Stomach ,DNA ,General Medicine ,Rats, Inbred F344 ,Hydrocarbons, Brominated ,Rats ,medicine.anatomical_structure ,Liver ,chemistry ,Gastric Mucosa ,Toxicity ,Female ,Food Science - Abstract
The genotoxic effects of methyl bromide were investigated in a DNA-binding study. [14C]Methyl bromide was administered to male and female F-344 rats orally, or by inhalation from a closed exposure system. DNA adducts were detected in the liver, lung, stomach and forestomach. [14C]3-Methyladenine, [14C]7-methylguanine and [14C]O6-methylguanine were identified using a combination of three different methods of hydrolysing DNA, followed by HPLC or gas chromatography-mass spectrometry. After both oral and inhalation exposure, the highest levels of methylated guanines, especially those of [14C]O6-methylguanine, were found in the stomach and forestomach of the rats. These results clearly demonstrate a systemic DNA-alkylating potential of methyl bromide.
- Published
- 1991
30. Combination of equilibrium dialysis, melting behaviour and circular dichroism spectroscopy in the study of genotoxic chemicals using ethylene oxide as a model substance
- Author
-
G. Snatzke, E. Hallier, U. Foest, H. Peter, B. Marczynski, and J. Hegemann
- Subjects
Circular dichroism ,Pyrimidine ,Ethylene oxide ,Chemistry ,Stereochemistry ,Guanine ,Uracil ,General Medicine ,Toxicology ,Thymine ,chemistry.chemical_compound ,Polymer chemistry ,Equilibrium constant ,Cytosine - Abstract
Ethylene oxide was incubated with different homobasic polynucleotides or dinucleotides. These were subsequently hybridized in equilibrium dialysis with their complementary or noncomplementary counterparts and the equilibrium constants determined. A change of the equilibrium constants after reaction with ethylene oxide corresponded with a shift in melting temperature of the reacted and hybridized macromolecular polynucleotides. The melting temperature was also changed when calf thymus DNA was reacted with ethylene oxide. In addition, the effect of ethylene oxide on the macromolecular single-stranded and double-stranded nucleic acids was investigated by studying the difference in rotation of circularly polarized light with the technique of circular dichroism spectroscopy. The changes in the spectra showed that ethylene oxide had altered the conformation of the hybridized double strands. These data indicated that binding sites in the pyrimidine bases of nucleic acid molecules, besides the previously known N-7 position in the purine base guanine, are attacked by ethylene oxide. There is evidence for the generation of N4-(2-hydroxyethyl)cytosine, O2-(2-hydroxyethyl)thymine and O4-(2-hydroxyethyl)uracil when the corresponding pyrimidine polynucleotides are incubated with ethylene oxide.
- Published
- 1991
31. Glutathione conjugation and cytochrome P-450 metabolism of methyl chloride in vitro
- Author
-
H. Peter, E. Hallier, S. Deutschmann, R. Jaeger, and H. M. Bolt
- Subjects
chemistry.chemical_classification ,Inhalation exposure ,medicine.medical_specialty ,Inhalation ,General Medicine ,Glutathione ,Metabolism ,Toxicology ,Chloride ,Cytosol ,chemistry.chemical_compound ,Endocrinology ,Enzyme ,Biochemistry ,chemistry ,Internal medicine ,medicine ,Carcinogen ,medicine.drug - Abstract
Possible carcinogenic properties of methyl chloride (CH 3 Cl) have been under discussion since an increase of renal tumours was observed in male B6C3F 1 mice after a 2-yr inhalation exposure to the substance. This was, however, only observed following exposure of male mice to the highest concentration level and not after exposure of females or F344 rats of both sexes. Accumulation of formaldehyde in the kidneys was thought to be responsible for tumour production. In the experiments presented here, cytosolic enzymes from the liver and kidneys of different mouse strains and F344 rats were incubated in head-space vials with methyl chloride or methyl bromide. Following equilibration, the decrease in the concentration of the gases was monitored by gas chromatography as a parameter for metabolic elimination. The metabolic turnover of the methyl halides was found to be significantly higher in female animals than in the males. In parallel experiments, the glutathione content of the liver and kidneys of mice exposed by inhalation to 1000 ppm methyl chloride was determined. In both organs, the glutathione content diminished rapidly after exposure to the methyl halide. The glutathione depletion was slightly greater in females than in males. Finally, the content of cytochromes P -450, P -420 and b5 was determined in liver and kidneys of different mouse strains by difference spectroscopy. Female mice were found to have a lower content of P -450 and b5 than males in the kidneys; there was no such sex difference in liver tissue. The results show that a sex difference in metabolism is unlikely to be responsible for the unique kidney tumour production in male B6C3F 1 mice. Other possible explanations are discussed.
- Published
- 1990
32. Influence of fuel properties, nitrogen oxides, and exhaust treatment by an oxidation catalytic converter on the mutagenicity of diesel engine emissions
- Author
-
A. Weigel, Thomas Brüning, Jürgen Bünger, Götz A. Westphal, Michael Müller, Jürgen Krahl, Olaf Jens Schröder, and Ernst Hallier
- Subjects
Salmonella typhimurium ,food.ingredient ,Health, Toxicology and Mutagenesis ,Toxicology ,Diesel engine ,complex mixtures ,Soybean oil ,Catalysis ,law.invention ,Fatty Acids, Monounsaturated ,chemistry.chemical_compound ,Diesel fuel ,food ,law ,Organic chemistry ,Plant Oils ,NOx ,Dichloromethane ,Vehicle Emissions ,Air Pollutants ,Mutagenicity Tests ,food and beverages ,Exhaust gas ,Esters ,General Medicine ,Soybean Oil ,chemistry ,Catalytic converter ,Microsomes, Liver ,Nitrogen oxide ,Nitrogen Oxides ,Rapeseed Oil ,Oxidation-Reduction ,Gasoline ,Nuclear chemistry ,Mutagens - Abstract
Particle emissions of diesel engines (DEP) content polycyclic aromatic hydrocarbons (PAH) these compounds cause a strong mutagenicity of solvent extracts of DEP. We investigated the influence of fuel properties, nitrogen oxides (NO( x )), and an oxidation catalytic converter (OCC) on the mutagenic effects of DEP. The engine was fuelled with common diesel fuel (DF), low-sulphur diesel fuel (LSDF), rapeseed oil methyl ester (RME), and soybean oil methyl ester (SME) and run at five different load modes in two series with and without installation of an OCC in the exhaust pipe. Particles from the cooled and diluted exhaust were sampled onto glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The mutagenicity of the extracts was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Without OCC the number of revertant colonies was lower in extracts of LSDF than in extracts of DF. The lowest numbers of revertant colonies were induced by the plant oil derived fuels. In three load modes, operation with the OCC led to a reduction of the mutagenicity. However, direct mutagenic effects under heavy duty conditions (load mode A) were significantly increased for RME (TA98, TA100) and SME (TA98). A consistent but not significant increase in direct mutagenicity was observed for DF and LSDF at load mode A, and for DF at idling (load mode E) when emissions were treated with the OCC. These results raise concern over the use of oxidation catalytic converters with diesel engines. We hypothesise that the OCC increases formation of direct acting mutagens under certain conditions by the reaction of NO( x ) with PAH resulting in the formation of nitrated-PAH. Most of these compounds are powerful direct acting mutagens.
- Published
- 2005
33. Neurobehavioral effects of experimental exposures to low levels of styrene
- Author
-
Andreas Seeber, Michael Schäper, Ernst Hallier, Klaus Golka, Christoph van Thriel, Meinolf Blaszkewicz, and Ernst Kiesswetter
- Subjects
Adult ,Male ,medicine.medical_specialty ,Air Pollutants, Occupational ,Audiology ,Toxicology ,Styrene ,Occupational medicine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Time of day ,Occupational Exposure ,medicine ,Reaction Time ,Humans ,Attention ,030212 general & internal medicine ,Morning ,business.industry ,General Medicine ,030210 environmental & occupational health ,3. Good health ,Surgery ,chemistry ,Toxicity ,Occupational exposure ,Nervous System Diseases ,business ,Psychomotor Performance - Abstract
Two experimental studies were conducted with the intention to simulate exposure characteristics of work places with styrene exposure and to investigate the risk for neurobehavioral impairments. In experiment I 16 volunteers (8 in the morning, 8 in the afternoon) were exposed to 0.5 and 20 ppm styrene on a constant level for 3 h. In experiment II 24 volunteers (12 in the morning, 12 in the afternoon) were exposed for 4 h to 0.5 and 20 ppm styrene on a constant level as well as to a changing exposure between 0.5 and 40 ppm with a TWA of 14 ppm. Simple reaction, choice reaction, attention, acute symptoms, and ratings for well-being were measured. Exposure related performance effects could not be detected. However, 6 h time change resulted in delayed choice reactions in the morning hours. Analysing acute symptoms and the state of well-being the impact of styrene did not reach adverse extents of impaired well-being.
- Published
- 2004
34. Glutathione-S-transferase (GST) theta polymorphism influences background SCE rate
- Author
-
Susanne E. Reich, Frederike A. Wiebel, Klaus R. Schröder, E. Hallier, Doris Dannappel, and H. M. Bolt
- Subjects
Adult ,Ethylene Oxide ,Male ,medicine.medical_specialty ,Erythrocytes ,Health, Toxicology and Mutagenesis ,Mitosis ,Sister chromatid exchange ,Biology ,Toxicology ,Substrate Specificity ,Cornified envelope ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Inducer ,Glutathione Transferase ,chemistry.chemical_classification ,Chi-Square Distribution ,Polymorphism, Genetic ,Smoking ,General Medicine ,Glutathione ,Enzyme ,Endocrinology ,Glutathione S-transferase ,chemistry ,Biochemistry ,Toxicity ,biology.protein ,Female ,Sister Chromatid Exchange - Abstract
Polymorphism of glutathione S-transferase theta (GSTT1) modulates the toxicity of halogenated alkanes and epoxides in humans. The enzymatic activity of glutathione S-transferase theta and its corresponding gene is lacking in about 30% of the central European population. It has now been demonstrated that the background rate for sister chromatid exchange (SCE) is affected by this particular polymorphism. Smoking as a known inducer of SCE was taken into account. A group of GSTT1-positive subjects exhibited lower SCE rates than GSTT1-negative individuals (7.55 +/- 0.77 versus 8.74 +/- 1.24 SCE/mitosis, respectively, p0.005). Non-smoking GSTT1-positive individuals showed the lowest SCE rate (7.26 +/- 0.71 SCE/mitosis), significantly lower than the rates of smoking GSTT1-positive and non-smoking GSTT1-negative subjects (8.14 +/- 0.55 SCE/mitosis and 8.12 +/- 0.88 SCE/mitosis, respectively, p0.025 in both cases). Smoking GSTT1-negative subjects exhibited the highest SCE rates (9.28 +/- 1.3 SCE/mitosis). It is hypothesized that GSTT1 is protective against background genotoxic damage. Since ethylene oxide is a proven substrate of GSTT1, the detoxification of this epoxide arising from endogenous ethylene may modulate SCE background rates.
- Published
- 1995
35. Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes
- Author
-
Thomas Schulz, Ernst Hallier, Michael Müller, Jürgen Bünger, Götz A. Westphal, and Soha Asgari
- Subjects
Genotype ,Cytochalasin B ,Health, Toxicology and Mutagenesis ,Pharmacology ,Toxicology ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Lymphocytes ,Chronic toxicity ,030304 developmental biology ,Glutathione Transferase ,0303 health sciences ,Micronucleus Tests ,Polymorphism, Genetic ,biology ,Dose-Response Relationship, Drug ,Thimerosal ,Preservatives, Pharmaceutical ,General Medicine ,3. Good health ,Actin Cytoskeleton ,Glutathione S-transferase ,chemistry ,030220 oncology & carcinogenesis ,Toxicity ,Immunology ,Micronucleus test ,biology.protein ,Thiomersal ,Drug Antagonism ,Genotoxicity ,Cell Division ,Mutagens - Abstract
Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.
- Published
- 2002
36. Genotoxicity of N-nitrosodicyclohexylamine in V79 cells in the sister chromatid exchange test and the single cell gel assay
- Author
-
Ernst Hallier, Gebel T, Michael Müller, and Götz A. Westphal
- Subjects
Neutral red ,Lysis ,Nitrosamines ,Health, Toxicology and Mutagenesis ,Dicyclohexylamine ,Sister chromatid exchange ,010501 environmental sciences ,In Vitro Techniques ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Cricetinae ,medicine ,Animals ,Cytotoxicity ,Carcinogen ,030304 developmental biology ,0105 earth and related environmental sciences ,Genetics ,0303 health sciences ,Chromatography ,Mutagenicity Tests ,General Medicine ,Comet assay ,chemistry ,Comet Assay ,Sister Chromatid Exchange ,Genotoxicity ,DNA Damage ,Mutagens - Abstract
Dicyclohexylaminexnitrite is used in chemical formulations as an anti-corrosion agent. N-Nitrosodicyclohexylamine (N-NO-DCHA) can be formed by nitrosation from dicyclohexylamine during the application of these formulations. As most of the nitrosamines are genotoxic carcinogens, the genotoxic potential of N-NO-DCHA was investigated in V79 Chinese hamster cells in the single cell gel assay and the sister chromatid exchange (SCE) test. In addition, N-NO-DCHA cytotoxicity was determined in the neutral red assay. Neutral red uptake was suppressed up to 50% after 24 h incubation at a concentration of approximately 135 microM. In the single cell gel assay, a significantly elevated and dose-dependent induction of DNA lesions was detected in a concentration range from 5 microM to 100 microM (P0.001). The use of proteinase K (1 mg/ml) in the lysing solution did not influence these results. In the SCE analysis, a significant induction of SCE was found at a minimum concentration of 5 microM N-NO-DCHA as well. A dose-dependent SCE induction could be detected up to the maximum concentration tested in the assay (100 microM). In conclusion, N-NO-DCHA is genotoxic in V79 cells in the single cell gel assay and the SCE test. With respect to human health hazard prevention, a substitution of dicyclohexylaminexnitrite in chemical formulations used to prevent corrosion is recommended.
- Published
- 2002
37. High-performance liquid chromatography/fluorescence detection of S-methylglutathione formed by glutathione-S-transferase T1 in vitro
- Author
-
Christian Heise, Michael Müller, Jürgen Bünger, Ernst Hallier, Thomas Schulz, and Michael Voss
- Subjects
0106 biological sciences ,Male ,Erythrocytes ,Health, Toxicology and Mutagenesis ,Metabolite ,Chloroformate ,010501 environmental sciences ,In Vitro Techniques ,Toxicology ,01 natural sciences ,High-performance liquid chromatography ,Hemolysis ,Enzyme catalysis ,Substrate Specificity ,chemistry.chemical_compound ,Humans ,Derivatization ,Chromatography, High Pressure Liquid ,0105 earth and related environmental sciences ,Glutathione Transferase ,Detection limit ,Chromatography ,biology ,Chemistry ,General Medicine ,Glutathione ,Enzyme assay ,Hydrocarbons, Brominated ,Spectrometry, Fluorescence ,biology.protein ,Methyl Chloride ,010606 plant biology & botany - Abstract
Glutathione-S-transferase T1 (GSTT1-1) is a major isoenzyme for the biotransformation of halomethanes. The enzyme activity is located, among other places, in human liver and erythrocytes and is subject to a genetic polymorphism. Metabolism of the halomethanes via GSTT1-1 yields S-methylglutathione (MeSG). A new HPLC assay for the enzymatic formation of MeSG was developed. The glutathione conjugate was derivatized with 9-fluorenylmethyl chloroformate, followed by reverse-phase HPLC with gradient elution and fluorescence detection. The limit of detection was as low as about 39 pmol MeSG on-column. Including derivatization and HPLC analysis, samples could be run at 42-min intervals, thus enabling a high sample throughput. The entire method was validated for analyte recovery (78.2%) and for variations in detector response with replicated injections (11.8%) and with analyses on each of 11 consecutive days (15.2%) with erythrocyte lysate incubations as the matrix. The time-, protein-, and substrate-dependences of the enzymatic catalysis with the model substrates methyl bromide (MeBr) and methyl chloride (MeCl) were studied. Due to its strong electrophilic character, MeBr caused a high level of spontaneous MeSG formation from glutathione in a protein-free medium and a substrate-trapping side reaction in the presence of proteins. Therefore, enzymatic MeSG formation rates may only be determined with MeBr concentrations of at least 3000 ppm in the presence of limited amounts of protein (e.g. 100 microl erythrocyte lysate). In contrast, MeCl showed a lower alkylating potential allowing enzymatic catalysis to be the dominant reaction in incubations with 10,000 ppm MeCl and 2 ml erythrocyte lysate.
- Published
- 2001
38. Comment on: Implications of latency period between benzene exposure and development of leukemia—A synopsis of literature
- Author
-
Sebastian Straube, Ernst Hallier, and Götz A. Westphal
- Subjects
0303 health sciences ,Pediatrics ,medicine.medical_specialty ,business.industry ,General Medicine ,Toxicology ,medicine.disease ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Latency stage ,medicine ,Benzene toxicity ,Occupational exposure ,Latency (engineering) ,business ,030304 developmental biology - Published
- 2010
39. Detection of cryptosporidia and Cryptosporidium parvum oocysts in environmental water samples by immunomagnetic separation-polymerase chain reaction
- Author
-
S. Hallier-Soulier and E. Guillot
- Subjects
animal diseases ,Fluorescent Antibody Technique ,Immunomagnetic separation ,Applied Microbiology and Biotechnology ,Polymerase Chain Reaction ,Sensitivity and Specificity ,law.invention ,Microbiology ,Apicomplexa ,Environmental water ,law ,Water Supply ,parasitic diseases ,Animals ,Polymerase chain reaction ,Cryptosporidium parvum ,biology ,Immunomagnetic Separation ,Water ,General Medicine ,Contamination ,biology.organism_classification ,Water sample ,Highly sensitive ,Evaluation Studies as Topic ,Biotechnology - Abstract
Cryptosporidium parvum has emerged as one of the most important new contaminants found in drinking water. Current protocols for the detection of cryptosporidia are time-consuming and rather inefficient. We recently described an immunomagnetic separation-polymerase chain reaction (IMS-PCR) assay permitting highly sensitive detection of C. parvum oocysts in drinking water samples. In this study, a second IMS-PCR assay to detect all cryptosporidial oocysts was developed, and both IMS-PCR assays were optimized on river water samples. A comparative study of the two IMS-PCR assays and the classical detection method based on an immunofluorescence assay (IFA) was carried out on 50 environmental samples. Whatever the type of water sample, the discrepancy in C. parvum detection between the IFA and IMS-PCR took the form of IFA-negative/IMS-PCR-positive results, and was caused mainly by the greater sensitivity of IMS-PCR as compared with IFA. Of the 50 water samples, only five tested positive for C. parvum using IMS-PCR, and could constitute a threat to human health. These results show that both IMS-PCR assays provide a rapid (1 d) and sensitive means of screening environmental water samples for the presence of cryptosporidia and C. parvum oocysts.
- Published
- 2000
40. Effects of variation in detoxification rate on dose monitoring through adducts
- Author
-
U. Föst, E. Hallier, Lars Ehrenberg, Margareta Törnqvist, F. Granath, and M. Leutbecher
- Subjects
0301 basic medicine ,Ethylene Oxide ,Erythrocytes ,Health, Toxicology and Mutagenesis ,Toxicology ,Risk Assessment ,Adduct ,03 medical and health sciences ,chemistry.chemical_compound ,Hemoglobins ,0302 clinical medicine ,Occupational Exposure ,Humans ,Glutathione Transferase ,chemistry.chemical_classification ,Polymorphism, Genetic ,030102 biochemistry & molecular biology ,Kinetic model ,Human blood ,Dose-Response Relationship, Drug ,General Medicine ,Environmental exposure ,Glutathione ,Environmental Exposure ,Dose monitoring ,Enzyme ,chemistry ,Biochemistry ,030220 oncology & carcinogenesis ,Inactivation, Metabolic ,Regression Analysis ,Hemoglobin ,Drug Monitoring - Abstract
1 Föst et al. ( Human & Experimental Toxicology 1991; 10: 25) have shown that ethylene oxide (EO) added to human blood gave rise to a higher level of adducts to haemoglobin (Hb) when the donors were deficient in an erythrocytic glutathione S-transferase (GST, later found to be GST-theta) than in blood from persons pos sessing this enzyme, and drew the conclusion that this polymorphism in detoxification rendered Hb adducts less suitable for biological monitoring. 2 By fitting a kinetic model to the data, the present study shows that the Hb adduct level gives a correct measure of the dose (concentration integrated over time) rele vant to risk estimation. 3 It does illustrate, however, the importance of knowing an individual's detoxification efficiency, when Hb adduct measurements are used to assess environmen tal exposure, for example in occupational surveillance.
- Published
- 1995
41. Macromolecular adducts in the use of methyl bromide as fumigant
- Author
-
E. Hallier, Andreas Müller, Hermann M. Bolt, and Hans Werner Goergens
- Subjects
Macromolecular Substances ,Serum albumin ,Sister chromatid exchange ,Alkylation ,Toxicology ,Adduct ,chemistry.chemical_compound ,Bromide ,Occupational Exposure ,Organic chemistry ,Humans ,Globin ,Cysteine ,Lymphocytes ,Chromatography ,biology ,Chemistry ,fungi ,General Medicine ,Environmental exposure ,Blood Proteins ,Blood proteins ,Globins ,Hydrocarbons, Brominated ,Fumigation ,biology.protein ,Seasons ,Sister Chromatid Exchange ,Protein Binding - Abstract
An HPLC method for analysis of blood protein adducts of methyl bromide was developed. With this method, the alkylated amino acid S-methylcysteine can be quantified both in globin and in serum albumin. The determination of these adducts was implemented in a field study on fumigators who use methyl bromide for the control of insects, nematodes and fungi. Sister chromatid exchange (SCE) was determined in the lymphocytes of the fumigators as an additional biomonitoring parameter. Exposure of persons living in the vicinity of fumigated objects to methyl bromide has been repeatedly reported in the past. The new method for determination of blood protein adducts can be applied for evaluation of such environmental exposure.
- Published
- 1994
42. Bacterial mutagenicity of 2-chloro-1,3-butadiene (chloroprene) caused by decomposition products
- Author
-
E. Hallier, Hermann M. Bolt, M. Leutbecher, Götz A. Westphal, Andreas Müller, and Meinolf Blaszkewicz
- Subjects
Salmonella typhimurium ,endocrine system ,Chloroprene ,Mutagenicity Tests ,Health, Toxicology and Mutagenesis ,fungi ,food and beverages ,1,3-Butadiene ,Mutagen ,General Medicine ,Toxicology ,medicine.disease_cause ,Gas Chromatography-Mass Spectrometry ,Ames test ,chemistry.chemical_compound ,chemistry ,medicine ,Pyrene ,Organic chemistry ,Propylene oxide ,Gas chromatography ,Genotoxicity - Abstract
Since the literature on genotoxicity of 2-chloro-1,3-butadiene (chloroprene) is controversial, the mutagenicity of this compound was reinvestigated with respect to its chemical stability. Because of the volatility of chloroprene, Ames tests with S. typhimurium TA 100 were carried out with gas-tight preincubation. Propylene oxide, a volatile direct mutagen, served as a positive control. Benzo[a]pyrene was used as a control for an indirect mutagen. Using this experimental regimen, freshly distilled chloroprene was not mutagenic. However, a mutagenic effect occurred linearly with increasing age of the chloroprene distillates. Aged chloroprene gave the same positive results whether preincubation was gas-tight or not. Analysis by gas chromatography (GC) revealed several decomposition products in aged chloroprene distillates. The direct mutagenicity towards TA 100 correlated with the integrated amounts of four of these substances; these substances always occurred in the same relative ratio. When chloroprene was kept under anaerobic conditions, products occurred with time which were partly different from those obtained under aerobic conditions. The direct mutagenicity of anaerobically aged chloroprene was only weak, but the mutagenic effect was enhanced about two- to threefold by addition of S9 mix. Partial identification of chloroprene decomposition products was done by gas chromatography-mass spectrometry (GC-MS): major byproducts of chloroprene, probably responsible for mutagenic properties of aged chloroprene samples, were cyclic chloroprene dimers.
- Published
- 1994
43. Ready-to-use in vitro blood–brain barrier model
- Author
-
Yannick Delplace, Lucie Dehouck, Emmanuel Sevin, D. Hallier-Vanuxeem, and Roméo Cecchelli
- Subjects
medicine.anatomical_structure ,business.industry ,medicine ,Ready to use ,General Medicine ,Pharmacology ,Toxicology ,Blood–brain barrier ,business ,In vitro - Published
- 2011
44. Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes
- Author
-
Thomas Langhof, M. Leutbecher, E. Hallier, Doris Dannappel, Hans Werner Goergens, Klaus R. Schröder, Hermann M. Bolt, and Andreas Müller
- Subjects
Ethylene Oxide ,Erythrocytes ,Health, Toxicology and Mutagenesis ,Population ,Sister chromatid exchange ,In Vitro Techniques ,Toxicology ,chemistry.chemical_compound ,Bromide ,medicine ,Humans ,Lymphocytes ,education ,Dichloromethane ,Glutathione Transferase ,education.field_of_study ,Methylene Chloride ,Polymorphism, Genetic ,biology ,Ethylene oxide ,General Medicine ,Glutathione ,Enzyme assay ,Hydrocarbons, Brominated ,Red blood cell ,medicine.anatomical_structure ,chemistry ,Biochemistry ,biology.protein ,Sister Chromatid Exchange - Abstract
A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population (“conjugators”) possess, whereas one quarter (“non-conjugators”) lack this specific activity. A standard method for the identification of conjugators and non-conjugators with the use of methyl bromide and gas chromatography (head space technique) is described. Three substrates of the polymorphic enzyme, methyl bromide, ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. All three substances led to a marked increase of sister chromatid exchanges (SCE) in the lymphocytes of the non-conjugators but not in those of conjugators. A protective effect of the glutathione-S-transferase activity in human erythrocytes for the cytogenetic toxicity of these chemicals in vitro is thus confirmed. Since the enzyme activity is not found in erythrocytes of laboratory animals, species extrapolations for risk assessment of methyl bromide, ethylene oxide and dichloromethane should be reconsidered.
- Published
- 1993
45. Identification of a cycloisoemericellin derivative as a novel mycotoxin in Aspergillus nidulans
- Author
-
Jürgen Bünger, Michael Müller, Götz A. Westphal, Ernst Hallier, Claudia Handrich, Stephanie Grond, and Melanie Quitschau
- Subjects
0106 biological sciences ,biology ,04 agricultural and veterinary sciences ,General Medicine ,Toxicology ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Aspergillus nidulans ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Identification (biology) ,Mycotoxin ,Derivative (chemistry) - Published
- 2009
46. Distribution of ethylene oxide in human blood and its implications for biomonitoring
- Author
-
H. M. Bolt, U. Föst, E. Hallier, H. Ottenwälder, and H. Peter
- Subjects
0301 basic medicine ,Ethylene Oxide ,Health, Toxicology and Mutagenesis ,Lymphocyte ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,Plasma ,0302 clinical medicine ,Blood plasma ,medicine ,Humans ,Carbon Radioisotopes ,Incubation ,chemistry.chemical_classification ,Blood Cells ,030102 biochemistry & molecular biology ,Ethylene oxide ,General Medicine ,Glutathione ,In vitro ,Enzyme ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Cytoplasm ,030220 oncology & carcinogenesis ,Environmental Monitoring - Abstract
The distribution of radioactivity following the incubation of human blood with radiolabelled ethylene oxide was investigated in vitro. After incubation, the individual blood samples were separated into lymphocytes and high (Mr > 10,000) and low (Mr < 10,000) molecular fractions of erythrocyte cytoplasm and blood plasma. The radioactivity was determined in each sample by liquid scintillation counting. In erythrocyte cytoplasm, the distribution of radioactivity showed marked interindividual differences and two distinct groups could be distinguished. The coincidence of these groups with 'conjugators' and 'non-conjugators', in terms of the enzymatic conjugation of methyl halides to glutathione in erythrocytes, suggests a common principle, such as enzyme polymorphism. Such polymorphism has been described for glutathione S-transferase μ in the human liver, an enzyme that efficiently conjugates epoxides. In the other blood compartments, the interindividual differences were either less significant or were not detectable. Binding products with various macromolecules in blood, such as haemoglobin or lymphocyte DNA, are being discussed as biological monitors for occupational exposure to ethylene oxide. The observation that erythrocytes exhibit interindividual differences as described above make binding products with haemoglobin less suitable for biological monitoring of ethylene oxide exposure than, for example, DNA adducts in lymphocytes.
- Published
- 1991
47. P2.02: Public health relevance of cattle allergic farmers in Germany
- Author
-
Dagmar Schippke, Hans Drexler, Nico Janicke, Heike Bickeböller, Astrid Heutelbeck, Ernst Hallier, Birgitta Kütting, and Christoph Langer
- Subjects
Statistics and Probability ,medicine.medical_specialty ,Health promotion ,Public health ,Environmental health ,medicine ,Relevance (information retrieval) ,General Medicine ,Business ,Statistics, Probability and Uncertainty - Published
- 2004
48. Mercury in infants given vaccines containing thiomersal
- Author
-
Götz A. Westphal and Ernst Hallier
- Subjects
No-observed-adverse-effect level ,010405 organic chemistry ,Chemistry ,chemistry.chemical_element ,Thimerosal ,General Medicine ,Pharmacology ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Mercury (element) ,chemistry.chemical_compound ,Micronucleus test ,Thiomersal - Published
- 2003
49. Purification and characterization of a new glutathione S-transferase, class θ, from human erythrocytes
- Author
-
Klaus R. Schröder, Ernst Hallier, David J. Meyer, Frederike A. Wiebel, Andreas M. F. Müller, and H. M. Bolt
- Subjects
Health, Toxicology and Mutagenesis ,General Medicine ,Toxicology - Published
- 1996
50. Absract
- Author
-
Marietta Kaszkin, Volker Kinzel, Karl Maly, Irina Bichler, Florian Lang, Hans H. Grunicke, R. Pepperkok, R. Jakobi, P. Lorenz, W. Ansorge, W. Pyerin, P. Borowski, M. Harbers, A. Ludwig, T. Kischel, H. Hilz, K. Eckert, A. Granetzny, J. Fischer, R. Grosse, V. Manch, S. Wehner, B. Kornhuber, U. Ebener, K. Müller-Decker, G. Fürstenberger, I. Vogt, F. Marks, G. Graschew, A. Küsel, W. Hull, W. Lorenz, H. W. Thielmann, Gisela H. Degen, Alexius Freyberger, A. Müller, M. Linscheid, Ulrike Hindermeier, Ute Jorritsma, K. Golka, W. Föllmann, H. Peter, H. M. Bolt, S. Monnerjahn, D. N. Phillips, A. Never, A. Seidel, A. R. Glatt, K. Wiench, E. Frei, P. Schroth, M. Wiessler, T. Schäfer, M. Hergenhahn, E. Hecker, D. Proft, P. Bartholmes, R. S. Bagewadikar, B. Bertram, N. Frank, Hanno Leibersperger, Michael Gschwendt, Friedrich Marks, S. Fasco, Peter Plein, Karin Schiess, Lothar Seidler, T. Jacobi, E. Besemfelder, M. Stephan, W. D. Lehmann, M. Grell, B. Thoma, P. Scheurich, Markus Meyer, Hans Grunicke, G. Jaques, B. Wegmann, K. Ravemann, Odilia Popanda, Heinz Walter Thielmann, H. Voss, U. Wirkner, Dieter Werner, D. Strand, A. Kalmes, H. -P. Walther, B. Mechler, S. Volker Schirrmacher, V. Kinzel, R. Hess, H. -G. Hanagarth, C. Hässler, G. Brandner, Christian Ertel, B. Gückel, V. Schirrmacher, B. A. Kyewski, U. Bogdahn, P. Jachimczak, J. Schneider, W. Brysch, W. Schlingensiepen, D. Drenkard, C. Behl, J. Winkler, R. Apfel, J. Meixensberger, K. Stulle, P. Marquardt, H. P. Vollmers, J. Müller, H. -K. Müller-Hermelink, M. Schuermann, G. Seemann, Angelika Ptok, M. Ptok, T. E. Carey, M. Steffen, U. C. Nitz, B. Everding, F. Hölzel, G. Kantwerk-Funke, G. Boll, K. S. Zänker, P. Hölzel, J. Heymanns, C. Hennig, M. Rotsch, K. Havemann, Jürgen R. Fischer, Sabine Stehr, Harald Lahm, Peter Drings, Peter H. Krammer, M. Kirsch, A. Strubel, A. Kist, R. Hinn, H. Fischer, A. Buttler, G. Schackert, S. Friedenauer, D. Lindner, B. Marczynski, H. Karcls, H. W. Goergens, B. Epe, E. Müller, D. Schütze, S. Boiteux, E. Eder, C. Deininger, C. Hoffman, E. Scherer, E. Vermeulen, H. J. van Kranen, J. Bax, R. A. Woutersen, C. F. van Kreijl, B. Schurich, H. Hagedorn, E. Kamp, G. Eisenbrand, B. Spiegelhalder, U. Bolm-Audorff, H. G. Bienfait, R. Preussmann, C. -D. Wacker, H. Kehl, Z. Akkan, J. Ries, M. Meger, S. E. Shephard, D. Gunz, W. K. Lutz, A. R. Tricker, R. Kurnar, M. Siddiqi, P. Mende, B. Pfundstein, A. Scholl, C. Janzowski, D. Jacob, P. Goelzer, I. Henn, H. Zankl, K. -H. Zimlich, Barbara Gansewendt, Ricarda Thier, K. R. Schroeder, E. Hallier, G. Moeckel, W. Heiden, M. Waldherr-Teschner, J. Brickmann, H. Roeser, G. Krauter, G. Scherer, A. Krätschmer, H. Hauenstein, F. Adlkofer, R. C. Fernando, H. H. Schmeiser, W. Nicklas, Wolfgang Pfau, David H. Phillips, S. Scheckenbach, S. Cantoreggi, Monika Leutbecher, H. Ottenwälder, U. Föst, P. M. Baumgart, H. -C. Kliem, S. Data, C. Pfeiffer, A. Fuchs, P. Schmezer, F. Kuchenmeister, B. L. Pool-Zober, U. M. Liegibel, B. L. Pool-Zobel, L. Steeb, H. Friesel, Th. Schneider, H. R. Scherf, A. Buchmann, R. Bauer-Hofmann, J. Mahr, M. Schwarz, R. Schmidt, F. Rippmann, B. Steinbauer, P. Zlfu, B. Bunk, W. Hefter, K. Klinga, M. R. Berger, L. W. Robertson, G. Luebeck, S. Moolgavkar, U. Torsten, M. Kowalczyk-Wagner, H. Weitzel, Ch. Zechel, H. Peters, F. Anders, S. Ambs, T. Kirchner, H. -G. Neumann, C. Einig, E. Eigenbrodt, D. Oesterle, E. Deml, G. Weisse, U. Gerbracht, H. Stumpf, E. Filsingcr, P. Bannasch, W. Muster, P. Cikryt, P. Münzel, E. Röhrdanz, K. W. Bock, H. -P. Lipp, T. Wiesmüller, H. Hagenmaier, D. Schrenk, A. Karger, G. Bauer, P. Höfler, M. Götschl, E. Viesel, J. Jürgensmeier, D. Schaefer, G. Picht, J. Kiefer, P. Krieg, R. Schnapke, S. Feil, E. Wagner, U. Schleenbecker, A. Anders, M. M. Gross, S. Unger, E. J. Stanbridge, Petra Boukamp, Ulrich Pascheberg, Norbert E. Fusenig, H. Abken, U. H. Weidle, F. Grummt, K. Willecke, R. Schäfer, A. Hajnal, I. Balmer, R. Klemenz, P. E. Goretzki, H. Reishaus, M. Demeure, H. Haubruck, J. Lyons, H. D. Röher, Sylvia Trouliaris, Angelika Hadwiger-Fangmeier, Elke Simon, Heiner Niemann, Teruko Tamura, G. Westphal, Elke Turner, H. Karels, M. Blaszkewicz, Helga Stopper, Dietmar Schiffmann, Umberto De Boni, M. Schuler, R. Schnitzler, M. Metzler, E. Pfeiffer, R. Aulenbacher, T. Langhof, K. R. Schröder, K. Saal, H. K. Müller-Hermelink, W. Henn, G. Seitz, P. Lagoda, A. Christmann, N. Blin, C. Welter, D. Adam, D. Fömzler, C. Winkler, W. Mäueler, M. Schartl, B. Theisinger, G. Schüder, U. Rüther, C. Nunnensiek, H. A. G. Müller, W. Rupp, M. Lüthgens, P. Jipp, I. Kinzler, M. Gulich, H. J. Seidel, O. H. Clark, F. McCormick, H. R. Bourne, F. Gieseler, F. Boege, H. Biersack, B. Spohn, M. Clark, K. Wilms, Fritz Boege, Frank Gieseler, Harald Biersack, Michael Clark, Klaus Wllms, Axel Polack, Lothar Strobl, Regina Feederle, Matthias Schweizer, Dirk Eick, Georg W. Bornkamm, M. Kopun, H. Scherthan, C. Granzow, P. Janiaud, D. Rueß, B. M. Mechler, P. G. Strauss, V. Erfle, M. Fritsche, C. Haessler, H. Christiansen, J. Schestag, N. M. Christiansen, F. Lampert, Wolfgang A. Schulz, Andreas Hasse, Helmut Sies, G. Orend, I. Kuhlmann, W. Doerfler, A. Behn-Krappa, I. Hölker, U. Sandaradura de Silva, Ute Smola, Dagmar Hennig, Angelika Hadviger-Fangmeier, Burkhard Schütz, R. Kerler, H. M. Rabes, G. Dölken, A. A. Fauser, R. Kerkert, U. Ragoczy, R. Fritzen, W. Lange, J. Finke, B. Nowicki, E. Schalipp, W. Siegert, R. Mertelsmann, U. Schilling, H. J. Sinn, W. Maier-Borst, E. A. Friedrich, E. Löhde, M. Lück, H. Raude, H. Schlicker, G. Barzen, E. Kraas, J. Milleck, R. Keymer, S. Störkel, T. Reichert, F. Steinbach, R. Lippold, W. Thoenes, W. Wagner, K. -A. Reiffen, A. Bardosi, D. Brkovic, H. -J. Gabius, B. Brandt, C. Jackisch, D. Seitzer, M. Hillebrand, F. A. Habermann, null Zeindl-Eberhart, null Evelyn, C. Robl, V. Röttgen, C. Nowak, H. -B. Richter-Reichhelm, V. Waldmann, B. Suchy, Ch. Zietz, M. Sarafoff, Richard Ostermayr, Hartmut M. Rabes, J. Lorenz, T. Friedberg, W. Paulus, R. Ferlinz, F. Oesch, E. Jähde, K. -H. Glüsenkamp, L. F. Tietze, M. F. Rajewsky, G. Chen, K. -J. Hutter, J. Bullerdiek, W. J. Zeller, M. Schirner, M. R. Schneider, P. Zbu, M. Gebelein, B. Naser-Hijazi, Nancy E. Hynes, M. Reinhardt, P. Heyl, D. Schmähl, P. Presek, U. Liebenhoff, D. Findik, G. H. Hartmann, C. Kliesch, F. Albert, S. Kunze, M. Wannnenmacher, J. Boese-Landgraf, E. Lorenz, D. Albrecht, M. Dulce, K. R. Aigner, N. Thiem, H. Müller, M. Leonardi, A. Justh, M. Lutz, E. Lang, C. W. v. d. Lieth, H. Sinn, B. R. Betsch, Jan Georg Hengstler, Jürgen Fuchs, Franz Oesch, F. J. Busch, A. B. C. Cato, G. Schied, W. Tang, B. Richter, C. Schaefer, D. K. Kelleher, P. Vaupel, D. Mundt, H. H. Bartsch, H. Meden, M. Meyer, K. Vehmeyer, R. Mull, W. Kuhn, S. Hoffmann, D. Berger, H. Fiebig, Ch. Moog, B. Luu, S. Frühauf, B. K. Keppler, A. Galeano, P. Valenzuela-Paz, T. Klenner, H. Stadler, G. Golomb, E. Breuer, R. Voegeli, P. Hilgard, H. R. Nowrousian, P. Aulenbacher, B. Winterhalter, C. Granson, M. Stöhr, H. Ponstingl, P. Drings, H. Osswald, S. B. Sobottka, E. Amtmann, G. Sauer, B. Hornung, S. Volland, S. Kahl, R. Gerspach, B. Matz, J. Schmidt, M. Lipp, G. Brehm, A. Luz, S. Wendel, P. G. Strauß, V. Erflte, S. Greehmann, A. Zobel, F. Kalkbrenner, G. Vorbrüggen, K. Moelling, T. Iftner, A. H. Müller, P. G. Fuchs, H. Pfister, Klaus Cichutek, Iris Treinies, Matthias Lang, C. Braun, J. Denner, S. Norley, R. Kurth, L. Music, O. D. Wiestler, A. Aguzzi, A. von Deimling, M. Schneemann, R. Elbl, P. Kleihues, H. Land, H. -P. Hohn, M. Höök, H. -W. Denker, W. Kemmner, K. Zaar, Peter A. Jones, R. Kath, M. Herlyn, P. Maier, H. P. Schawalder, J. Elsner, W. Parzefall, E. Erber, R. Sedivy, R. Schulte-Hermann, J. Hemmer, P. Tomakidi, P. Boukamp, D. Breitkreutz, N. E. Fusenig, F. Kallinowski, W. Strauss, A. L. Brownell, I. D. Bassukas, G. Vester, B. Maurer-Schultze, L. Langbein, H. Kosmehl, D. Katenkamp, Eberhard Spiess, Günther Trefz, Werner Ebert, Peter Jordan, Dieter Kübler, Rosemarie B. Lichtner, Marion Wiedemuth, Annette Kittmann, Axel Ullrich, Khashayarsha Khazaie, Aiga Kowitz, Guni Kadmon, Peter Altevogt, U. H. Frixen, J. Behrens, J. Schipper, M. Sachs, H. Birchmeier, R. Hackenberg, Th. Hawighorst, J. Hofmann, H. Beato, K. -D. Schulz, C. Erbil, M. Maasberg, L. A. Kunz, A. Simm, G. Adam, W. Mueller-Klieser, Andreas M. Kaufmann, Michael Stoeck, A. Hülsen, S. Game, M. Donnelly, H. -J. Stark, K. -H. Schlingensiepen, U. Kurzik-Dumke, B. Phannavong, D. Gundacker, E. Gateff, S. Gabius, S. S. Joshi, H. Franz, N. J. John, R. Grümmer, H. W. Denker, M. W. Gross, and U. Karbach
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Cancer Research ,Oncology ,General Medicine - Published
- 1991
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