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Biomedical subjects

M Schümann

Publications and source records attributed to M Schümann.

15 recordsLinked to original sources
PubMed2005

Dermal and bronchial symptoms in children: are they caused by PAH containing parquet glue or by passive smoking?

OBJECTIVE: In 1997 a new source of potential polycyclic aromatic hydrocarbon (PAH) exposure was discovered: very high levels of (PAHs) and benzo-a-pyrene (BaP) were detected in household dust from former American Forces housing in Frankfurt am Main, Germany, built in 1955/1956. This contamination was caused by a parquet glue containing coal tar, the use of which was formerly a standard building practice in Germany. Children were considered to be at special risk for exposure to PAHs when playing on the floor via mouthing. Therefore, the children's symptoms and complaints were analysed for association with PAH contamination in parquet glue and household dust as well as with internal exposure to PAHs via determination of 1-hydroxypyrene in urine samples. PARTICIPANTS AND METHODS: Two hundred and eighty seven children <6 years of age living more than 12 months in the former US-housing estates are enrolled in this analysis, representing 22.3% of the children <6 years of age living there. Their spot urine samples were analysed for 1-hydroxypyrene. The level of BaP in parquet glue and in household dust was available in the homes of 215 and 212 children, respectively. There were no hints for differences in PAH contamination in parquet glue or in household dust of the participants' flats compared to the flats of the non responders. In 246 cases data on environmental tobacco smoke exposure at home was known as well. Data on symptoms and complaints observed by their parents during the preceding 12 months (1-year prevalence) were obtained using the ISAAC questionnaire (modified). RESULTS: The following 1-year prevalences were reported: 15% itching eczema in elbows, 10% itching and urticaria, 6% itching in the palate and throat, 20% sneezing and running nose or stuffed nose, 15% nosebleed; 25% wheezing, 42% dry cough, and 60% frequent infectious disease. No consistent associations between symptoms and BaP in parquet glue or in household dust or urinary levels of 1-hydroxypyrene in the children could be found. However, associations between symptoms and exposure to environmental tobacco smoke at home were to be seen, significant for dermal and bronchial symptoms. CONCLUSION: Informed about PAHs in parquet glue and household dust many parents demanded for total redevelopment of their flats. According to statistical evaluation of the children's symptoms, observed by their parents, no hints for an association with exposure via BaP in parquet glue or household dust were found. However, significant associations between symptoms and the exposure to environmental tobacco smoke were observed, especially bronchial and dermal symptoms. Therefore instead of redevelopment of flats with parquet glue containing coal tar, intensified information on the harmful effects of passive smoking in childhood seems to be mandatory.

Adhesives↗
PubMed1999

Study of Burkitt lymphoma cell line proteins by high resolution two-dimensional gel electrophoresis and nanoelectrospray mass spectrometry.

We paper describe a mass spectrometric approach generally applicable for the rapid identification and characterization of proteins isolated by two-dimensional gel electrophoresis (2-DE). The highly sensitive nanoflow-electrospray mass spectrometry employing a quadrupole-time of flight mass spectrometer was used for the direct identification of proteins from the peptide mixture generated from only one high resolution 2-DE gel without high performance liquid chromatography (HPLC) separation or Edman sequencing. Due to the high sensitivity and high mass accuracy of the instrument employed, this technique proved to be a powerful tool for the identification of proteins from femtomole amounts of materials. We applied the technique for the investigation of Burkitt lymphoma BL60 cell proteins. This cell line has been used as a model to assign apoptosis-associated proteins by subtractive analysis of normal and apoptotic cells. From the nuclear fraction of these cells, 36 protein spots were examined, from only one micropreparative Coomassie Brilliant Blue R-250 stained gel, after proteolytic digestion by matrix assisted laser desorption ionization (MALDI) and nanospray mass spectrometry (MS). In combination with database searches, of 33 proteins were successfully identified by nanospray-MS/MS-sequencing of up to eight peptides per protein. Three proteins were new proteins not listed in any of the available databases. Some of the identified proteins are known to be involved in apoptosis processes, the others were common proteins in the eukaryotic cell. The given technique and the protein data are the basis for construction of a database to compare normal and apoptosis-induced cells and, further, to enable fast screening of drug impact in apoptosis-associated processes.

Amino Acid Sequence↗
PubMed1999

[Human biomonitoring of polychlorinated biphenyls in 130 exposed elementary school children].

In the classroom air on a primary school polychlorinated biphenyls were present in a wide range extending to 10.220 ng/cbm; in a side room even 19.550 ng/cbm were measured. The school was closed down, a flame retardant paint was detected to be the main source of this contamination. 130 differently exposed persons gave blood specimens for measurement of PCB concentrations. Compared with a comparative reference collective of equal age reported by the analysing laboratory, the PCB blood concentrations of 92 actual pupils were even lower. A comparison with five near-representative child collectives of South Germany did not show any obvious difference. The reference values of the German Human Biomonitoring Commission were exceeded by 4 of 92 pupils for PCB 138, by 6 pupils for PCB 153 and by 6 pupils for PCB 180. In a group of 9 teachers and 1 cleaning person the median values of reference collectives of equal age reported by the analysing laboratory were exceeded by 8 persons for PCB 138, 7 persons for PCB 153 and 8 persons for PCB 180. The 95. Percentiles of these reference collectives and the reference values of the German Human Biomonitoring Commission were not exceeded. In bivariate and multiple regression analyses the data of 92 actual pupils showed positive associations between blood levels of PCB and age as well as nursing period, a negative association between PCB blood concentrations and body-mass index and a weak influence by gender (boys had lower blood concentrations). In addition, the results of multiple regression analyses showed (with the exception of the analyses of PCB 180 without controlling for gender) a significant influence of PCB concentrations in indoor air on PCB blood concentrations. This association could not be detected in bivariate analyses, and in comparison to the mentioned main influence variables it was obviously weaker. But basing on the results of the multiple regression analyses one can calculate an increase of PCB blood concentration by 3% multiplicatively if PCB indoor concentrations increase by 1000 ng/cbm.

Air Pollutants↗
PubMed1999

[Uncertainty analysis of quantitative risk assessment in temporally variable exposures: model observations based on biological and epidemiological risk models].

Unit risks used for quantitative cancer risk assessment are defined for constant lifetime exposures. The condition of temporal stability, however, usually is not fulfilled in environmental health applications. In practice, cancer risks for time-dependent exposures are often estimated by calculating lifetime average exposure, assuming a mean life expectancy of 70 years. In the present paper we discuss the question whether this is an appropriate procedure considering various variants of multi stage and epidemiological relative risk models. For this purpose, lifetime risks for time dependent exposures as calculated according to the respective model assumptions, were compared with lifetime risks estimated by the lifetime average exposure approach. As typical exposure histories in environmental health applications we studied exposures either limited to the first 5 years of life (children scenario) or limited to duration of employment (30th to 65th year of age; occupational scenario). The consideration of multistage models (Armitage-Doll- and Moolgavkar-Venzon-Knudson model) in general would not induce serious bias in risk estimation when exposures are limited to middle ages (occupational scenario). On the other hand, when exposures occur only in very young ages or only in very old ages the risk estimated by using lifetime average exposure is not comparable with the predictions of multistage models. Whereas the degree of possible underestimation is bounded by factors well below 10, the amount of possible overestimation is unbounded and may become arbitrarily high, when exposures concentrate in extreme ages. In a second part of the study we investigated different relative risk models, taking lung cancer as an example. The models differed with respect to assumptions on latent periods and moderating effects of age at exposure and age at risk. The simulations showed that the unit risk concept is appropriate for the occupational scenario. For the children scenario results strongly depend on the assumptions made. Whereas the degree of possible underestimation is acceptable, in some models the degree of possible overestimation may become arbitrarily high. Both parts of the study showed that bias induced by using lifetime average exposure is acceptable when exposures are limited to middle ages. On the other hand, the unit risk concept should not uncritically be applied to exposures limited to early childhood (e.g., in kindergartens or due to mouthing activities). Depending on the assumptions made, lifetime risk may either be moderately underestimated or grossly overestimated. Without additional knowledge on mechanisms or latency period risk estimations are of questionable value. With respect to exposures in childhood regulation should concentrate on initiating substances or substances known to have long latent periods, respectively. With respect to cancers which occur relatively frequent already in childhood specific considerations are recommended.

Adult↗
PubMed1998

PCDD/PCDF indoor exposure in day-care centers and PCDD/PCDF blood concentrations of female employees.

We determined blood concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in 41 female employees with previous exposure to pentachlorophenol-based wood preservatives from 10 day-care centers in the Hamburg, Germany, area. We compared the blood concentrations with estimated age-dependent reference values and analyzed the correlation between PCDD/PCDF indoor air exposure and blood concentrations. The analyses based on the PCDD congeners 1,2,3,4,7,8-, 1,2,3,6,7,8-, and 1,2,3,7,8,9-hexaCDD (hexaCDD), 1,2,3,4,6,7,8-heptaCDD (heptaCDD), octaCDD, and the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalents calculated according to the international NATO-CCMS model (I-TEQ). In comparison to the estimated reference values, the blood concentrations of hexaCDD and I-TEQ spread around the mean estimate. Data for octaCDD scattered in some cases distinctly above the upper confidence limit. Reference values for heptaCDD could not be estimated. The correlation between PCDD/PCDF indoor air exposure and PCDD/PCDF blood concentrations was examined by linear multiple regression analysis considering different exposure variables and taking confounders into account. Analyses were carried out with the total study group and with a restricted subgroup. Associations were shown between the PCDD/PCDF indoor air concentrations and blood concentrations for heptaCDD and for the I-TEQ, whereas hexaCDD showed no association. OctaCDD showed a negative association in the total study group and no association in the subgroup analysis. In summary, the analyses showed no clear association between PCDD/PCDF indoor air exposure in day-care centers and PCDD/PCDF blood levels of female employees previously exposed to wood preservatives. By contrast, the results consistently indicated a positive association between PCDD/PCDF blood concentrations and exposure to wood preservatives in private homes.

Adult↗
PubMed1997

The tendency of magainin to associate upon binding to phospholipid bilayers.

Fluorescence energy transfer (FET) from [Trp16]-magainin-2-amide (Trp-Mag) and [D-Ala15,D-Trp16]magainin-2-amide (DD-Trp-Mag) to N(alpha)-dansyl-magainin-2-amide (DNS-Mag) was used to study the association of magainin 2 analogs bound to phosphatidylglycerol vesicles. As shown by circular dichroism and fluorescence spectroscopy, the all-L-analogs exist in a helical conformation and are completely bound to the lipid membrane. The observed FET between Trp-Mag and DNS-Mag is rather small and increases with the DNS-Mag surface concentration. The experimentally determined transfer efficiency is lower than predicted for monomeric magainin analogs randomly distributed exclusively at the outer leaflet of lipid vesicles. These observations can be explained by two different models of spatial distribution for the monomeric magainin analogs. The first model takes into account translocation of magainin which might result in a uniform distribution of magainin at the inner and outer vesicle leaflets. The second model assumes that at least one shell of lipids exists between two magainin molecules, thus reducing the probability of direct contact. Both models explain the measured FET without any contribution of stable associates of magainin analogs. Furthermore, for Trp-Mag and DD-Trp-Mag, an identical energy transfer efficiency was observed, although the nonhelical double-D substituted analog should have a significantly reduced association tendency resulting in decreased FET. Our conclusion that the observed FET is not the result of magainin association is confirmed by the equivalence of the measured energy transfer efficiencies.

Anti-Infective Agents↗
PubMed1996

Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes.

An amphipathic model peptide, KLALKLALKALKAAKLA-NH2, and its complete double D-amino acid replacement set was used to analyze the process of peptide binding at lipid vesicles of different surface charge and to determine the structure of the lipid-bound peptides using CD spectroscopy. The relationship between peptide helicity, model membrane permeability, and biological activity has been studied by dye release from liposomes and investigation of antibacterial and hemolytic activity. The accumulation of cationic KLAL peptides at and the membrane-disturbing effect on bilayers of high negative surface charge were found to be dominated by charge interactions. Independent of any structural propensity, the cationic peptide side chains bind to the anionic phosphatidylglycerol moieties. The charge interactions hold the peptides at the bilayer surface, where they may disturb preferentially lipid headgroup organization by formation of peptide-lipid clusters. In contrast, KLAL peptide interaction with bilayers of low negative surface charge is highly dependent on peptide helicity. With decreasing amounts of anionic phosphatidylglycerol in the bilayer the membrane-disturbing effect of KLAL and other helical analogs substantially increases despite drastically reduced binding affinity. Less helical peptides exhibit reduced bilayer-disturbing activity, showing that the hydrophobic helix domain is decisive for binding at and inducing permeability in membranes of low negative surface charge. It is suggested that hydrophobic interactions drive the penetration of the amphipathic peptide structure into the inner membrane region, thus disturbing the arrangement of the lipid acyl chains and causing local disruption. On the basis of the proposed model for membrane disturbance, interactions modulating antibacterial and hemolytic activity are discussed.

Amino Acid Sequence↗
PubMed1996

Conformational and functional study of magainin 2 in model membrane environments using the new approach of systematic double-D-amino acid replacement.

Systematic double-D-amino acid replacement of adjacent amino acids has been used to study the secondary structure of the amphiphilic, antibiotic peptide magainin 2 amide (M2a) by circular dichroism spectroscopy. Bound to liposomes, the secondary structure of the peptide is characterized by a weak alpha-helix in the N-terminus and a stable alpha-helix between residues 9 and 21. The lack of conformational differences in the peptide when bound to vesicles of varying negative charge density indicates marked independence of the structure from electrostatic forces. The similarity of the helicity profiles observed for double D-isomers bound to vesicles and in the presence of sodium dodecyl sulfate micelles (SDS) clearly shows that SDS can mimic magainin-lipid interactions. In contrast, in 1:1 trifluoroethanol/buffer (v/v), the peptide exhibits a weak alpha-helix extended from the N- to the C-terminus. Dye release experiments from vesicles of phosphatidylglycerol showed that double-D-amino acid substitution only in the region of the stable helix results in a reduction of the membrane-permeabilizing ability. On vesicles with a reduced amount of acidic phospholipids, double-D-amino acid substitution in any position leads to a drastic reduction of peptide-induced membrane permeabilization. Whereas the activity of M2a on phosphatidylglycerol was found to be mainly electrostatically determined, hydrophobic interactions play a decisive role in the interaction with vesicles of reduced negative charge density. Fluorescence investigations of tryptophan-containing analogs of high and low helicity showed that differences in the location of the chromophores of the membrane-bound peptides do not exist.

Amides↗
PubMed1996

Conformational differences of ovine and human corticotropin releasing hormone. A CD, IR, NMR and dynamic light scattering study.

The differences in the conformational properties of ovine (o) and human (h) CRH in aqueous solution, structure-inducing TFE and in the presence of detergent micelles and lipid vesicles have been investigated by circular dichroism, Fourier transform infrared spectroscopy, NMR and dynamic light scattering. o-CRH was found to exist as a monomer with little regular structure in dilute aqueous solution. Association at concentrations higher than 10-3 mol/L results predominantly in dimers. The induction of a substantial amount of intermolecular beta-structure seems to be the result of interactions of the C-terminal hexapeptide and the N-terminal region 6-12 of o-CRH chains in antiparallel orientation. In contrast, h-CRH exhibits a high tendency of association which is highly sensitive to the pH. The formation of tetramers at millimolar peptide concentration is related to a helical content of ca. 50%. The potentially helical, highly hydrophobic region 6-20 enlarged by more hydrophobic residues in position 23 and 25 is proposed to stabilize the h-CRH associates. In the presence of structure inducing TFE (> 40% v) both CRH peptides exist as monomers. o-CRH reveals about 72% helicity, in h-CRH the formation of about 85% helix is observed. The differences in helicity of the two CRH molecules are located in the C-terminal heptapeptide, as concluded on the basis of NMR studies. Both peptides bind to detergent micelles at pH 4 as well as 7.4 associated with an increase in the alpha-helical content. Interaction of the two peptides with DMPC vesicles was found exclusively at pH 4. Above the phase transition temperature of DMPC the alpha-helical content in h-CRH increases slightly; however, o-CRH reveals a substantial amount of beta-type structure. The intramolecular type of beta-structure is associated with a deeper insertion of the o-CRH region 6-12 into the hydrophobic region of the lipid bilayer, whereas the corresponding region of h-CRH is kept in the bilayer surface. The higher helicity of h-CRH might explain to some extent its higher affinity to the CRH receptor, CRH antibodies and the CRH binding protein.

Animals↗
PubMed1989

Limitations of epidemiology in assessing cancer risk from environmental sources.

There is much discussion on how to define an "acceptable risk" for a population typically exposed to low doses of environmental carcinogens. One proposal claims that all risks which are not "observable" should be considered acceptable (e.g. BYRD/LAVE 1987). It is demonstrated for example in cancer deaths due to environmental carcinogens that, for methodological reasons the acceptance of this criterion means the toleration of considerable health risks for society. From a preventive point of view methods of extrapolation seem to be more appropriate to handle "living with the uncertainty".

Carcinogens, Environmental↗
PubMed1989

Regional population risk evaluation for multiple inhalation hazards.

An approximative cartographic estimation method for individual and population risk values has been developed and tested. The absolute and relative weights of multiple inhalation hazards were computed in a regionally differentiated way for the city of Hamburg (FRG).

Administration, Inhalation↗