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Biomedical subjects

M Lohmeyer

Publications and source records attributed to M Lohmeyer.

12 recordsLinked to original sources
PubMed2005

Preventive measures to reduce bioaerosol exposure during refuse collection: results of field studies in the real-life situation.

The aim of the present research project was to investigate and evaluate technical and organisational measures targeted at bioaerosol reduction during the refuse collection and to determine the exposure of refuse collectors to dust, fungi and endotoxins in an on-the-job situation with different vehicle technologies and states of hygiene. The following technical factors were found to influence the bioaerosol concentration at the refuse collector's workplace: compaction method, lifting device control, rave rail height, hopper depth, design of intake area and dust interception. For instance, notably higher total fungal counts were recorded with rotating drum compaction than with packer plate compaction. A hinged lid closure at the lifting device in conjunction with a suction unit induced a positive effect. In addition, the automatic lifting system had a positive influence on rear-end loaders, as did loading operation control from the closed driver's cab on side loaders. Regular internal and external high-pressure cleaning of the lifting device at intervals of not more than 14 days is recommended as a basic rule for vehicle hygiene.

Aerosols↗
PubMed2005

A description of the standardized measurement procedures and recommended threshold limit values for biological hazards in Germany.

On the basis of EU directives 89/391/EEC (to encourage improvements in the safety and health of workers at work) and 2000/54/EC (on the protection of workers from risks related to exposure to biological agents at work), biological hazards at work have to be assessed and preventive measures have to be introduced in all member states of the EU. In Germany, national legislation (Biological Agents Ordinance - BioStoffV and Technical Rules on Biological Agents, TRBA) and recommendations of workers' compensation boards define standardized methods for the assessment of airborne mold, bacteria, and endotoxins. This article describes policies and practices in Germany for measurement of airborne bioaerosols and for interpretation of measurements relative to the standards. As an example, methods and results of measurements in agriculture are shown. The standardized measurement procedures proved suitable for use in livestock buildings. The results of the exploratory measurements in different livestock buildings confirmed the often high concentrations of airborne biological hazards in agriculture that are reported in the literature.

Agricultural Workers' Diseases↗
PubMed2002

Bioaerosol exposure during refuse collection: results of field studies in the real-life situation.

To determine the bioaerosol exposure of refuse collectors, field measurements were performed under real working conditions within the framework of a research project. Influencing variables such as different types of refuse, community structure, collection interval and season were taken into account. Overall, 1612 samples were taken in towns of Westfalia, Germany. With workplace levels on a scale of 10(3) to less than 10(4) CFU/m3 for the loader, the results show a surprisingly low total fungi concentration in comparison with earlier studies. Total bacteria concentrations, in contrast, were largely on a scale of 10(4) CFU/m3, with 10(5) CFU/m3 being registered sporadically, especially in apartment-block districts. Endotoxin levels were high especially in the summer months, occasionally reaching values of more than 50 EU/m3, whereas they were normally below 10 EU/m3 in autumn and winter. Inside the cab, the exposure level for the entire spectrum was at least one power of ten lower. The factors believed to account primarily for the low total fungi concentration were workplace hygiene, the prevailing 1-week collection interval, and the low in-process exposure time resulting from the effective deployment of automatic lifting devices. In contrast, the type of refuse was not found to have a significant influence.

Aerosols↗
PubMed1997

Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human cripto.

Cripto, also known as human teratocarcinoma-derived growth factor 1 (TDGF-1), contains a 40 amino acid region with some similarity to the epidermal growth factor (EGF) domain. However, sequence homology is largely restricted to the classical cysteine/glycine motif with only limited similarities in other regions. Significant differences to human EGF include the absence of all seven residues between the two N-terminal half-cystines and a five-residue shorter loop between the third and fourth half-cystines. We examine the hypothesis that, in spite of these differences, cripto can adopt the characteristic EGF-like 1-3, 2-4, 5-6 disulfide bond pattern. A comparative structural model of the growth factor cripto was constructed on the basis of its similarity to EGF, transforming growth factor alpha (TGF-alpha), and the EGF-like domain of human clotting factor IX. The predicted disulfide bridges and disulfide-bridged loops were analyzed and appear viable in the modeled structure. Moreover, to ascertain the importance of disulfide arrangement for cripto bioactivity, two 47-residue peptides were synthesized and then refolded using either a simple oxidative or a controlled sequential refolding protocol. The cripto peptides were tested for their ability to stimulate MAP-kinase activity, for inhibition of beta-casein induction, and for Shc phosphorylation in MDA-MB 453 human mammary carcinoma cells and HC-11 mouse mammary epithelial cells. Data suggest that cripto does adopt the 1-3, 2-4, 5-6 disulfide pattern and thus forms the classical EGF-like fold in spite of the significant deletions within the folding domain. The predicted structure of cripto shows some of the characteristics of both the ErbB1- and ErbB3/ErbB4-binding growth factors.

Amino Acid Sequence↗
PubMed1997

Cripto enhances the tyrosine phosphorylation of Shc and activates mitogen-activated protein kinase (MAPK) in mammary epithelial cells.

Cripto-1 (CR-1), a recently discovered protein of the epidermal growth factor (EGF) family, was found to interact with a high affinity, saturable binding site(s) on HC-11 mouse mammary epithelial cells and on several different human breast cancer cell lines. This receptor exhibits specificity for CR-1, since other EGF-related peptides including EGF, transforming growth factor alpha, heparin-binding EGF-like growth factor, amphiregulin, epiregulin, betacellulin, or heregulin beta1 that bind to either the EGF receptor or to other type 1 receptor tyrosine kinases such as erb B-3 or erb B-4 fail to compete for binding. Conversely, CR-1 was found not to directly bind to or to activate the tyrosine kinases associated with the EGFR, erb B-2, erb B-3, or erb B-4 either alone or in various pairwise combinations which have been ectopically expressed in Ba/F3 mouse pro-B lymphocyte cells. However, exogenous CR-1 could induce an increase in the tyrosine phosphorylation of 185- and 120-kDa proteins and a rapid (within 3-5 min) increase in the tyrosine phosphorylation of the SH2-containing adaptor proteins p66, p52, and p46 Shc in mouse mammary HC-11 epithelial cells and in human MDA-MB-453 and SKBr-3 breast cancer cells. CR-1 was also found to promote an increase in the association of the adaptor Grb2-guanine nucleotide exchange factor-mouse son of sevenless (mSOS) signaling complex with tyrosine-phosphorylated Shc in HC-11 cells. Finally, CR-1 was able to increase p42(erk-2) mitogen-activated protein kinase (MAPK) activity in HC-11 cells within 5-10 min of treatment. These data demonstrate that CR-1 can function through a receptor which activates intracellular components in the ras/raf/MEK/MAPK pathway.

Animals↗
PubMed1995

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids.

A panel of 25 different lipid agents was evaluated for in vitro activity against HT29 human colon carcinoma and HL60 promyelocytic leukaemia cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships seen with this series, including those for four sets of positional or stereoisomers, indicate that specific receptor proteins are unlikely as targets for anti-tumour lipid (ATL) action. Additional data confirm the lack of involvement of the platelet-activating factor receptor in particular and suggest that metabolic stability is a most important determinant of ATL activity. More detailed studies, with 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET18-OCH3) and (+/-)-2-(Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2- yl]methoxyphosphinyloxy)-N,N,N,-trimethylethaniminium hydroxide (SRI 62-834), suggest three different modes of activity, depending on drug concentration and exposure time. Low doses of up to 5 microM in standard serum-containing medium cause population growth arrest after prolonged exposure. Growth arrest was associated with a leaky G2/M block as determined by flow cytometry. These effects are reversible. Intermediate concentrations (5-40 microM) were cytotoxic, causing a net reduction in cell numbers after 2-3 days. At even higher concentrations, all lipids caused rapid, direct membrane lysis. When the clonogenic assay was used to assess the effects of ATLs, most agents reduced colony formation at concentrations above 5 microM. However, some compounds proved stimulatory at nanomolar concentrations, suggesting that they might possess mitogenic properties. These results, particularly those concerning the concentration and time dependence, may be relevant to current clinical trials with ether lipids.

Animals↗
PubMed1994

Stimulation of intracellular free calcium increases by platelet-activating factor in HT29 colon carcinoma cells. Spectrofluorimetric and preliminary spatio-temporal analysis using confocal laser scanning fluorescence imaging microscopy.

We examined the ability of platelet-activating factor (PAF) and its lyso derivative (lyso-PAF) to elicit increases in intracellular free calcium concentration ([Ca2+]i) in HT29 human colon carcinoma cells. Using spectrofluorimetric analysis with indo-1 as the [Ca2+]i reporter molecule, we found that 1-10 microM concentrations of both lipids stimulated substantial, reversible, monophasic [Ca2+]i elevations. Evidence was obtained that the two lipids may act via specific receptors to release Ca2+ from internal stores. Homologous desensitization was observed in both cases and PAF and lyso-PAF were also able to desensitize cells reciprocally (heterologous desensitization). The potent PAF receptor antagonist WEB 2086 (3-[4-(chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2, 4]triazolo-[4,3-a][1,4]-diazepin-2-yl]-1-(4-morpholinyl)-1-propano ne) successfully blocked PAF-induced [Ca2+]i elevations, but did not affect rises in response to lyso-PAF, suggesting that lyso-PAF may act through a different cellular receptor or mechanism. Higher concentrations (> 10 microM) of PAF resulted in non-reversible [Ca2+]i elevations which were caused by Ca2+ influx following membrane lysis. However, the WEB 2086 insensitivity of these effects and the resultant cellular toxicity clearly showed that such events were mechanistically distinct from the reversible [Ca2+]i elevations apparently operating via WEB 2086-sensitive receptors. Preliminary spatio-temporal observations, using confocal microscopy and fluo-3 as the [Ca2+]i reporter molecule, suggested that PAF can also induce [Ca2+]i elevations in the absence of cell lysis in monolayer HT29 cells. Visual impressions were obtained of cellular and subcellular heterogeneity and of [Ca2+]i oscillations in responding cells. However, these need to be interpreted with caution because of the intrinsic limitations of the methodology, particularly using non-ratiometric dyes. The significance of a receptor-mediated, reversible elevation of [Ca2+]i by sub-toxic concentrations of PAF in HT29 colon cancer cells remains to be elucidated, but it is tempting to speculate that PAF might function as a locally acting signalling mediator in these and possibly other tumour cells.

Calcium↗
PubMed1993

The role of intracellular free calcium mobilization in the mechanism of action of antitumour ether lipids SRI 62-834 and ET18-OMe.

Membrane-active antitumour ether lipids such as ET18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and SRI 62-834 ((+-)-2-(Hydroxy[tetrahydro-2-(octadecyloxy) methylfuran-2-yl] methoxyl phosphinyloxy)-N,N,N-trimethylethaniminium hydroxide) are selectively cytotoxic to tumour cells in vitro. Their precise mechanisms of action are unclear, but they are known to have effects on cell membranes and cell signalling. A previous report suggested that ether lipids cause a biphasic sustained rise in intracellular free calcium [Lazenby et al., Cancer Res 50: 3327-3330, 1990]. We show here that the second phase is an experimental artefact due to cell membrane permeabilization by ether lipids in serum-free buffers. In serum-free medium, the membrane toxicity of antitumour ether lipids was increased 50-60 fold, when compared to medium containing 10% serum. Membrane disruption was neither dependent on extracellular calcium, nor modulated by preloading cells with the calcium chelators bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or 2-[[2-[bis(carboxymethyl)amino]-5-methylphenoxy]methyl]-6- methoxy-8-[bis(carboxymethyl)amino]quinoline. This indicates that the mechanism of membrane damage by ether lipids does not involve changes in calcium homeostasis. Using indo-1 and fura-2 as calcium probes, we established that lower concentrations of antitumour ether lipids do elicit a genuine monophasic and transient rise in intracellular free calcium, predominantly mobilized from internal stores. This acute calcium agonist activity of ether lipids is distinct from the inhibitory effects on cell signalling reported previously after more prolonged exposure. It appears that the calcium elevation induced by antitumour ether lipids is unlikely to be instrumental in their selective and potent antitumour activity.

Antineoplastic Agents↗
PubMed1993

Long-Term Production of Ergot Peptides by Immobilized Claviceps purpurea in Semicontinuous and Continuous Culture.

The semicontinuous and continuous production of pharmaceutically useful ergot peptides with immobilized Claviceps purpurea could be demonstrated. A key aspect was the presence of high concentrations of CaCl(2) (96.9 mM) to give marked prolongation of the productive phase, and cultivation in a bubble column reactor became possible. Restriction of the phosphate supply avoided an otherwise problematic massive increase of outgrowing hyphae.

Journal Article↗
PubMed1992

Lack of enantio-selectivity in the in vitro antitumour cytotoxicity and membrane-damaging activity of ether lipid SRI 62-834: further evidence for a non-receptor-mediated mechanism of action.

SRI 62-834 ([tetrahydro-2-(octadecycloxy)methylfuran- 2-yl]methoxylphosphocholine; CRC 86-05; NSC 614383) is a cyclic antitumour ether lipid (AEL) with a novel, but ill-defined, mechanism of action. AELs are believed to act on membranes and cell signals, but the precise mechanisms of selectivity are unclear. Receptor-mediated mechanisms can often be identified by the differential activity of the individual stereoisomers of a drug. We have therefore compared the R- and S-enantiomers of SRI 62-834 for: (1) cytotoxicity against the human HT29 colon carcinoma cell line using a tetrazolium dye reduction assay and (2) membrane-damaging effects monitored by 51Cr radiolabel release. The tetrazolium assay revealed near-identical mean ID50 values around of 2-3 microM for the R- and S-isomers as well as for the racemic mixture. Moreover, pre- and co-incubation of the cells with the potent platelet-activating factor (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine;PAF) receptor antagonist WEB 2086BS (3-[4-(chorophenyl)-9-methyl-6H-thieno[3,2- f][1,2,4]triazolo-[4,3-a][1,4]-diazepin-2-yl]-1-(4- morpholinyl)-1-propanone) had no effect on the cytotoxicity of either isomer or the racemate. Short-term membrane damage was not evident at low micromolar concentrations and between 139 and 163 microM either lipid was required to release 50% of the incorporated 51Cr label. Again, there was no difference in potency between the enantiomers and the racemate. Coincubation with WEB 2086BS also failed to modulate the membrane-lytic potency of the AELs. These results indicate that the site(s) of cytotoxic action of SRI 62-834 is (are) not stereospecific and also appear to rule out the involvement of a conventional PAF receptor in the mechanism of action of SRI 62-834.

Antineoplastic Agents↗