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PubMed2005

Model system for testing the efficacy of antioxidants in muscle foods.

The objective of this research was to study the effect of the antioxidants, delta-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ), and propyl gallate in a model system of lean muscle and canola oil and to compare the effects with those in minced herring. Two carrier solvents with different dielectric constants (epsilon), ethanol (epsilon = 24) and oil (epsilon= 2), were used. Oxidation was measured using thiobarbituric acid reactive substances (TBARS) and sensory analysis. In both the lean muscle-canola oil model system and in herring muscle, the hydrophilic antioxidants, propyl gallate and TBHQ, were more effective in providing oxidative stability than the lipophilic antioxidants, delta-tocopherol and BHT. The oxidative stability of a cod muscle-canola oil system in the presence of propyl gallate, and delta-tocopherol was not affected by the dielectric constant of the carrier solvent, while BHA was more effective as an antioxidant when added in the polar solvent ethanol.

Animals↗
PubMed1995

Hospital information systems modeling and simulation: the right method for the right objective.

The aim of this paper is to present an "instruction for use" on the information systems modeling and simulation methods in the case of a Hospital Information System. Firstly, a right modeling is defined as the right modeling method for the right objective and secondly, it exposes a short state of the art on these methods, the objectives of modeling and simulation for the Information System of a hospital and the application of the right method for the right objective. Finally it insists on the concrete aspects of how to realize modeling and simulation and the advantages of such an approach.

Computer Simulation↗
PubMed1987

The guinea-pig isolated atrium as a model system for the central actions of selected CNS stimulant and depressant drugs. Part 1: 3,3-Diakylglutarimide homologues and related drugs.

The 3H-noradrenaline pretreated, spontaneously beating, guinea-pig atrial preparation has been used as a model system to study the presynaptic and postsynaptic actions of selected drugs with stimulant (bemegride, pentylenetetrazol, picrotoxin, strychnine and 4-methyl-4-n-propylpiperidine hydrochloride), depressant (pentobarbitone, hydroxydione, trimethadione, 3-methyl-3-n-alkylglutarimide where alkyl = butyl, amyl or hexyl, 4-methyl-4-n-propylpiperidone-2 hydrochloride, chlordiazepoxide and chlorpromazine) or dual stimulant-depressant (3-methyl-3-n-propylglutarimide and 5-ethyl-5-(1,3-dimethylbutyl) barbiturate and its (+) and (-) enantiomers) actions in the central nervous system of the mouse. 3H-Noradrenaline efflux and force and rate of atrial contraction were used as parameters of atrial function. With the exception of strychnine, picrotoxin and 4-methyl-4-n-propylpiperidine hydrochloride, which appear to act by different central mechanisms, there is good correspondence between the actions of the test drugs on the force of atrial contraction and in the CNS of the mouse. Thus, stimulant drugs increase and depressant drugs decrease the force of atrial contraction, while dual stimulant-depressant drugs in low concentrations increase, and in higher concentrations, decrease the inotropic response. A similarly good correspondence generally exists between mouse and atrium with respect to the relative stimulant and depressant potencies of the test drugs, additive stimulation or depression for pairs of like-acting drugs and 'analepsis' and 'anticonvulsant activity' for drugs with opposed central actions. No such relationships were found using tritium efflux or the chronotropic response as parameters of atrial function. Thus, the guinea-pig atrial preparation appears to be a good model system in which to demonstrate the acute CNS actions and interactions of the majority of the test drugs. Their positive and negative inotropic effects on the atrium have been explained in terms of a membrane phase distribution hypothesis of drug action, and their ability to facilitate or impede, respectively, the movement of Ca2/ across the atrial sarcolemmal membrane. It is proposed that these drugs may act by similar mechanisms at responsive sites in the brainstem reticular formation and related areas in the mouse. These may be primarily excitatory noradrenergic synapses integrated functionally with presynaptic or independent inhibitory GABAergic terminals.

Animals↗
PubMed1988

Molecular mechanisms of exocytosis: the adrenal chromaffin cell as a model system.

1. The release of neurotransmitters, hormones, and enzymes involves exquisitely regulated events which ultimately result in the fusion of the secretory vesicle with the cell's plasma membrane, releasing the vesicle contents into the extracellular space. 2. The biochemical and cellular mechanisms mediating exocytosis have been extensively studied in a model system of primary cultured adrenal chromaffin cells. 3. This paper briefly reviews current understanding, and directions of future studies in exocytosis using this model system.

Adrenal Medulla↗
PubMed1998

Interaction of the major epitope region of HIV protein gp41 with membrane model systems. A fluorescence spectroscopy study.

Fluorescence spectroscopy (both steady-state and time-resolved) was used to study the fragment 579-601 of gp41 ectodomain (HIV-1), a highly conserved sequence and major epitope, regarding (1) structural information, (2) interaction with membrane model systems, and (3) location in the phospholipid bilayer. The peptide was characterized both in its monomeric (after reduction of the disulfide bond between cysteine residues) and in the dimeric forms. The change of the fluorescence anisotropy between monomer and dimer was rationalized on the basis of energy migration, and a distance between the two tryptophan (Trp) residues of approximately 6 A was obtained. Using different fluorescence spectroscopy approaches, it was demonstrated that, despite the fact that monomeric gp41 fragment incorporates in the membrane model systems studied, the dimeric form does not interact with these vesicles. A methodology based on the increase of the mean fluorescence lifetime averaged by the preexponentials was derived, to obtain the partition coefficient of the peptide in the different lipid systems. Fluorescence quenching using lipophilic probes and red edge excitation shift (REES) were used to study the location of the gp41 fragment in the membrane. It was concluded that the Trp residue is located in a shallow position, near the interface. The REES results show an uncommonly large wavelength shift (18 nm) for the gp41 fragment incorporated in the membrane. Our results are consistent with a "two steps" model for the gp41 fusion mechanism similar to the one proposed for influenza virus hemagglutinin.

Amino Acid Sequence↗
PubMed2002

Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

Alleles↗
PubMed1983

Isolated rat hepatocytes as a model system for screening chelators for use in cadmium intoxication.

The utility of isolated rat hepatocytes as a model system for screening potential chelators in treatment of Cd intoxication was studied. The ability of the chelators diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), 2,3-dimercaptosuccinic acid (DMSA), diethyldithiocarbamic acid (DDC), d,1-penicillamine (PEN), nitrilotriacetic acid (NTA), and 2,3-dimercaptopropanol (BAL) to decrease the cellular concentration of Cd was correlated with the previously reported effectiveness of these agents in the treatment of Cd intoxication in vivo. The results of cellular studies with either control or metallothionein-induced hepatocytes were compared to the in vivo effect of the chelators administered before or after the induction of metallothionein, respectively. The effects of DTPA, EDTA, DDC, and BAL in the hepatocyte model screening system correlated well with their reported in vivo effects. The results with NTA, PEN, and DMSA were not correlated as well but were explained by the relative differences between in vivo doses versus in vitro concentrations of the respective chelators. Therefore, the proposed model for screening potential chelators for use in cadmium intoxication appears to be a system which may prove to be an economical and rapid method to facilitate the search for efficacious chelators.

Animals↗
PubMed2002

Studies toward the synthesis of (-)-zampanolide: preparation of N-acyl hemiaminal model systems.

[structure: see text] Synthesis of N-acyl hemiaminal model systems related to the side chain of the antitumor natural product zampanolide is reported. Key steps involve oxidative decarboxylation of N-acyl-alpha-amino acid intermediates, followed by ytterbium triflate mediated solvolysis. Evidence for stabilization of the N-acyl hemiaminal moiety in model compounds by an intramolecular hydrogen-bonding network is described.

Antineoplastic Agents↗
PubMed1997

[Approaches for a systemic modelling of health programs].

The aim of this paper is to achieve a systemic model to describe a health programme taking into account the influence of the actors. The data were collected via interviews with 15 people collaborating on two programmes: screening of colorectal cancer using the Hémoccult II test in France, and restructuring health services in a district in Guinea. The results stress that a public and community health programme can be described as a self-organizing, dynamic, observing and observed system. With a systemic approach, a programme can be modelled according to three steps. First, preliminaries: although initially motivated by the wish to improve the system, the intervention on it meets with resistance to any change. This stage proposes to open an "intervention space" including the definition of an appropriate framework, and the modelling of the problematic situation. Second, change: this stage brings new standards in the system. The more useful, the more suited to the mind of the collaborators and the more integrated into the existing social networks, the more easily the changes are welcomed. Finally, autonomization: the regulations of the system contribute to maintain the new standards, and thus to strengthen the changes. In conclusion, in the initial purpose to improve its operational capabilities, an intervention on a local part of the social and health system may, on the contrary, cause troubles. The systemic approach proposes a scenario in order to deal with this complexity. It also gives new insights for planning, implementing, and assessing health programmes.

Colorectal Neoplasms↗
PubMed1996

The drosophila neuromuscular junction: a model system for studying synaptic development and function.

The Drosophila neuromuscular junction has attracted widespread attention as an excellent model system for studying the cellular and molecular mechanisms of synaptic development and neurotransmission. In Drosophila the advantages of invertebrate small systems, where individual cells can be examined with single-cell resolution, are combined with the powerful techniques of patch-clamp analysis and molecular genetics. In this review we examine myogenesis and motoneuron development, the problems of axon outgrowth and target selection, the differentiation of the synapse, and the mechanisms of both synaptic function and plasticity in this model genetic system.

Animals↗
PubMed2002

Embryonic stem cells provide a powerful and versatile model system.

Embryonic stem (ES) cells are pluripotent stem cells that differentiate both in vitro and in vivo into cell types derived from each of the three embryonic germ layers. ES cells and their close relatives, embryonal carcinoma (EC) cells and embryonic germ (EG) cells, have been used extensively as model systems for studying early mammalian development. This work has led to important insights into the mechanisms that control embryogenesis at the molecular and cellular levels. This chapter focuses on the use of ES cells as an in vitro model system for studying cellular differentiation and reviews several areas where important progress has been made. Impressive progress has been made in the isolation and characterization of ES cells from many species, including humans. Significant progress has also been made in the development of culture conditions that help direct the differentiation of ES cells to specific cell types that form during myogenesis, angiogenesis, hematopoiesis, neurogenesis, and cardiogenesis. The ability to inactivate virtually any gene in ES cells by gene targeting has vastly improved our understanding of the roles played by specific genes at the cellular and organismic levels. Moreover, ES cells and EC cells have been used widely to investigate how specific genes are turned on and turned off in the course of differentiation. In this connection, DNA array technology has been used to identify genes regulated when ES cells differentiate. The final section of this chapter discusses how work with ES cells is shaping our understanding of stem cells, mammalian development, and cell replacement therapy.

Animals↗
PubMed1978

Stereological model system for free cells and base-line data for human peripheral blood-derived small T-lymphocytes.

T-lymphocytes derived from human peripheral blood and passed through a nylon-wool column, were employed to develop and test a new stereological model system for free spherical cells, allowing a quantitative characterization of the cell and its components at the ultrastructural level. Electron micrographs were recorded in a hierarchical manner at three different levels of magnification and subjected to point counting procedures. The resulting parameters were expressed in relation to various reference compartments, both absolute and relative. Results indicated that the average volume of a small, non-activated T-lymphocyte was 103.8 micron3, the nuclear volume 47.5 micron3 and the cytoplasmic volume 55.9 micron3. On the average, the cytoplasm contained 30 mitochondria, 0.7 micron3 RER-cisternae, 0.2 micron3 cisternae and vesicles of the Golgi apparatus and about 231,000 free ribosomes (most of them single). The ratio of eu- to heterochromatin volume was 0.5. The design and application of the stereological model system are discussed with regard to dynamic studies of a variety of free cells, such as macrophages, neutrophilic granulocytes and various lymphocytes.

Adult↗
PubMed1998

Primmorphs generated from dissociated cells of the sponge Suberites domuncula: a model system for studies of cell proliferation and cell death.

Sponges (Porifera) represent the lowest metazoan phylum; they have been shown to be provided with the characteristic metazoan structural and functional molecules. One autapomorphic character of sponges is the presence of high levels of telomerase activity in all cells (or almost all cells, including somatic cells). In spite of this fact previous attempts to cultivate sponge cells remained unsuccessful. It was found that dissociated sponge cells do not replicate DNA and lose their telomerase activity. In addition, no nutrients or metabolites have been detected that would stimulate sponge cells to divide. In the present study we report the culture conditions required for the formation of multicellular aggregates from dissociated single cells of Suberites domuncula, termed primmorphs. These primmorphs are formed in seawater without addition of further supplements, and have an organised tissue-like structure; they have been cultured for more than 5 months. Cross-sections revealed a distinct external layer covered by a continuous pinacoderm, and a central zone composed primarily of spherulous cells. After their association into primmorphs, the cells turn from the telomerase-negative state into the telomerase-positive state; a telomerase level of 4.7 total product generated (TPG) units/5 x 10(3) cell equivalents has been determined. Moreover, a major fraction of the cells in the primmorphs undergoes DNA synthesis and hence has the capacity to grow. Applying the BrdU-labelling and detection assay it is demonstrated that up to 33.8% of the cells in the primmorphs are labelled with BrdU after an incubation period of 12 h. It is proposed that the primmorph system described here is a powerful novel model system to study basic mechanisms of cell proliferation and cell interaction, as well as of morphogenesis, ageing and apoptosis.

Animals↗
PubMed1989

Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability.

Caco-2 cells develop morphologic characteristics of normal enterocytes when grown on plastic dishes or nitrocellulose filters. The purpose of this study was to determine whether Caco-2 cells undergo similar differentiation when grown on Transwell polycarbonate membranes, and to study the suitability of Caco-2 monolayers as an intestinal epithelial transport model system. Transepithelial electrical resistance values after confluence were 173.5 omega.cm2 and remained unchanged through day 17. Permeabilities to the water-soluble fluid-phase markers that do not permeate the membrane, Lucifer yellow CH, [14C]inulin, [14C]polyethylene glycol, and [3H] dextran were less than 0.25% of the administered amount per hour after day 10. Qualitative evaluation of uptake and permeability to horseradish peroxidase confirmed the similarity in uptake and barrier properties between this cell system and the small intestinal epithelial layer. We conclude that Caco-2 cells grown on collagen-coated polycarbonate membranes should represent a valuable transport model system for the small intestinal epithelium.

Adenocarcinoma↗
PubMed2006

Simulating transient ventricular interaction using a minimal cardiovascular system model.

A minimal closed-loop cardiovascular system (CVS) model has been developed that can simulate ventricular interaction due to both direct interaction through the septum and series interaction through the circulation system. The model is used to simulate canine experiments carried out to study the transient response of the left ventricle due to changes in right ventricle pressures and volumes. The model-simulated trends in left and right ventricle pressures and volumes, septum deflection and arterial flow rates are compared with the experimental results. In spite of the limited physiological data available describing the animals, the model is shown to capture all the transient trends in the experimental data. This is the first known example of a physiological model that can capture all these trends. The model is then used to illustrate the separate effects of direct and series interactions independently. This study proves the value of this modelling method to be used in conjunction with experimental data for delineating and understanding the factors that contribute to ventricular dynamics.

Animals↗
PubMed2004

Evaluation of a new model system for studying the formation of heterocyclic amines.

Heterocyclic amines (HAs) are an important class of food mutagens and carcinogens, which can be found in cooked meat and fish. Increasing heating temperatures and times usually increase mutagenic activity in meat and meat extracts during cooking. We developed a model system, which allows to examine the effects of precursor composition and heating conditions (time and temperature) on the formation of HAs in meat. Homogenized and freeze dried meat samples (beef, pork chops, chicken breast and turkey breast) are heated with diethylene glycol in closed vials under stirring in a thermostated heating block. After an appropriate sample preparation (extraction and clean-up) ten different HAs were measured by HPLC analyses with gradient elution and mass selective detection. The time courses of HA-formation in the different kinds of meat at varying heating temperatures were determined up to heating times of 30 min. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was the most abundant HA in these experiments and reached the highest concentrations in the beef meat samples, as did the other HAs (MeIQ, AalphaC) at 220 degrees C in the heating block under stirred conditions. Additionally the influence of the antioxidant TBHQ (t-butylhydroquinone) on the formation of HAs in the model system was tested. However TBHQ effected only slight reductions of HA formation in all kinds of meat.

Amines↗
PubMed2006

An extensible spatial and temporal epidemiological modelling system.

BACKGROUND: This paper describes the Spatiotemporal Epidemiological Modeller (STEM) which is an extensible software system and framework for modelling the spatial and temporal progression of multiple diseases affecting multiple populations in geographically distributed locations. STEM is an experiment in developing a software system that can model complex epidemiological scenarios while also being extensible by the research community. The ultimate goal of STEM is to provide a common modelling platform powerful enough to be sufficient for all modelling scenarios and extensible in a way that allows different researchers to combine their efforts in developing exceptionally good models. RESULTS: STEM is a powerful modelling system that allows researchers to model scenarios with unmixed populations that are not uniformly distributed and in which multiple populations exist that are being infected with multiple diseases. It's underlying representational framework, a graph, and its software architecture allow the system to be extended by incorporating software components developed by different researchers. CONCLUSION: This approach taken in the design of STEM creates a powerful platform for epidemiological research collaboration. Future versions of the system will make such collaborative efforts easy and common.

Animals↗
PubMed2002

NADH model systems functionalized with Zn(II)-cyclen as flavin binding site-structure dependence of the redox reaction within reversible aggregates.

The relative positions and conformations of the prosthetic group FAD and the cofactor NADH have been remarkably conserved within the structurally diverse group of flavin enzymes. To provide a chemical rational for such an obviously optimal relative disposition of the redox partners for efficient reaction we have synthesized NADH models with Zn(II)-cyclen substituents for reversible flavin binding in water. Altogether, four of these model systems with systematically varying spacer length between the recognition site and the redox active dihydronicotinamide were prepared. The binding of these model systems to riboflavin tetraacetate was confirmed by potentiometric pH titration in water and their reaction with flavin was followed by UV-vis spectroscopy in aqueous media under physiological conditions. The measurements reveal a significant rate enhancement of up to 175 times that of an intermolecular reaction. Moreover, a strong dependence of the reaction rate on the spacer length was observed, which clearly shows that within the dynamic reversible assembly only the optimal relative disposition of the redox partners ensures an efficient redox reaction.

Binding Sites↗