Biomedical subjects

M Comber

Publications and source records attributed to M Comber.

8 recordsLinked to original sources

PubMed2005

European union system for the evaluation of substances: the second version.

This publication presents major changes in the assessment of the risks of chemicals to human health and the environment as implemented in the second version of the European Union System for the Evaluation of Substances, EUSES 2.0. EUSES is a harmonised quantitative risk assessment tool for chemicals. It is the PC-implementation of the technical guidelines developed within the framework of EU chemical legislation for industrial chemicals and biocides. As such, it is designed to support decision making by risk managers in government and industry and to assist scientific institutions in the risk assessment for these substances. The development of EUSES 2.0 is a co-ordinated project of the European Chemicals Bureau, EU Member States and the European chemical industry. Several model concepts, the technical background and the user interface of EUSES have been improved considerably. Major changes in the environmental assessment such as the implementation of emission scenario documents for industrial chemicals and biocides, the addition of the marine risk assessment, the enhancement of the regional model to include global scales, and improvements in the secondary poisoning and environmental effects modelling will be discussed. The update of the human risk assessment module in EUSES focuses on the risk characterisation for both threshold and non-threshold substances with, among others, the introduction of assessment factors. The performance of EUSES is illustrated in an example showing the human and environmental risk assessment of a sanitation disinfectant for private use.

Animals↗

PubMed2005

Base-line model for identifying the bioaccumulation potential of chemicals.

The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important mitigating factor was found to be metabolism. Accordingly, a simulator for fish liver was used in the model, which has been trained to reproduce fish metabolism based on related mammalian metabolic pathways. Other significant mitigating factors, depending on the chemical structure, e.g. molecular size and ionization were also taken into account in the model. The results (r(2)=0.84) obtained for a training set of 511 chemicals demonstrate the usefulness of the BCF base line concept. The predictability of the model was evaluated on the basis of 176 chemicals not used in the model building. The correctness of predictions (abs(logBSF(Obs)-logBCF(Calc))=0.75)) for 59 chemicals included within the model applicability domain was 80%.

Animals↗

PubMed2003

Experiences in robotically enhanced IMA-preparation as initial step towards totally endoscopic coronary artery bypass grafting.

AIM: To evaluate the feasibility of robotically enhanced preparation of internal mammary arteries (IMA). METHOD: Via three trocars in left thoracic wall the left, right or both IMA were skeletonized under CO(2) insufflation and single lung ventilation using electrocautery. RESULTS: In 12 months, 26 LIMA, five BIMA and one RIMA were dissected. In five patients, the procedure had to be determined (IMA injury (two), respiratory insufficiency (two), and heart penetration (one)). Mean intrathoracic pressure was 9.7+/-1.5 mmHg. Mean time for LIMA and RIMA dissection was 66.7+/-21.1 and 99.2+/-8.7 min, respectively. In 10 patients, pericardium was incised and course of LAD assessed. However, in two patients, this coronary did not correlate with LAD. Time for instrument change depended on type of tool (cautery blade: 24.9+/-13.1 s, clip applier 72.8+/-28.4 s). CONCLUSION: Robotic dissection of IMA is reasonable. However, life-threatening complications can barely be managed due to inadequate tools and excessive time for instrument change. Incorrect determination of coronaries can result in misplaced anastomoses.

Aged↗

PubMed2003

Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling.

Education↗

PubMed1988

Structural characterization of the 9-10S estradiol receptor from calf uterus.

An affinity chromatography-based method has been developed for estrogen receptor isolation which requires the inclusion of sodium molybdate in purification buffers for maintaining the large 9-10S form of the receptor. The protein products obtained from affinity chromatography of calf uterine receptor extracts or from extracts presaturated with estradiol have been analyzed by gel electrophoresis under denaturing conditions. Major estrogen sensitive proteins were peptides with Mr approximately 90,000, 65,000 and 50,000. Two additional proteins (60,000 and 53,000) of lower abundance and with demonstrated estrogen sensitivity were also observed. Affinity labeling with [3H]tamoxifen aziridine identified the Mr 65,000 protein as the estrogen receptor and suggested that the Mr 60,000, 53,000 and 50,000 peptide components were derived proteolytically from this parent unit. The 90,000 mol. wt component was readily dissociated from heparin-sepharose immobilized estrogen receptor by elution with low salt buffers without molybdate. Peptide mapping experiments indicated that the 90,000 mol. wt component was not related to the Mr 65,000 and 50,000 estrogen receptors, but confirmed the smaller binding unit to be a proteolytic fragment of the 65,000 mol. wt receptor. The results suggest that the 90K protein associates non-covalently with the Mr 65,000 estrogen binding unit as a nonhormone binding component of the 9-10S receptor.

Animals↗

PubMed1987

The amino-terminal sequence of the 85-90K nonhormone binding component of the molybdate-stabilized estradiol receptor from calf uterus.

The first six N-terminal amino acid residues of the 85-90K non-estrogen binding component of the calf uterine, molybdate-stabilized estradiol receptor have been determined by Edman degradation. After affinity chromatography of the stabilized receptor oligomer, the 85-90K unit was purified to homogeneity by preparative gel electrophoresis using electroelution for protein recovery. Inverse-gradient high performance liquid chromatography provided the 85-90K protein suitable for amino-terminal sequence analysis.

Amino Acid Sequence↗

PubMed1983

Differentiation of malicious and non-malicious fire-alarm calls using multidimensional scaling.

A pilot study was carried out to determine whether malicious and non-malicious fire alarm calls could be distinguished on the basis of their psycholinguistic attributes. Eight malicious and eight non-malicious calls were compared in terms of the number of speech errors of various kinds in the call. Using multi-dimensional scalogram analysis (MSA-I), it was possible to differentiate the two types of call on the basis of the over-all configuration of speech behaviour within the call.

Crime↗

PubMedDate not supplied

A comparison of 11 beta-chloromethylestradiol and tamoxifen aziridine as affinity labeling reagents for estrogen receptors.

The tritium-labeled from of 11 beta-chloromethylestradiol was prepared by metal hydride reduction of the 17-keto derivative. Affinity labeling experiments were carried out using [3H] 11 beta-chloromethylestradiol and [3H]tamoxifen aziridine with estrogen receptor from crude, calf uterine cytosol and partially purified (heparin-sepharose chromatography) preparations. Both compounds formed highly stable receptor complexes. Estrogen specific, covalent binding, however, was indicated only for [3H]tamoxifen aziridine. An equilibrium dissociation constant of 2.8 x 10(-10) M was determined for the receptor-[3H] 11 beta-chloromethylestradiol interaction. Measurement of hormone dissociation kinetics at 30 degrees C revealed a slow, single phase dissociation of 11 beta-chloromethylestradiol from the receptor (dissociation rate constant, 1.3 x 10(-3) min-1). This contrasted with the normal biphasic dissociation pattern of estradiol in which the dissociation rate constant for the slower component was 16.7 x 10(-3) min-1. The results indicate that 11 beta-chloromethylestradiol readily converts the estrogen receptor to a high affinity binding form and suggest that the radiolabeled hormone may prove useful for studies of estrogen action.

Affinity Labels↗