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PubMed1989

[The role of the cytoskeletal components in cell culture in collagen gel as a model system of vitreous contraction].

We previously reported a cell culture system in artificial collagen gel as a model system of vitreous contraction. In this report, the epithelium cultured in the collagen gel elongated and induced gel contraction. The motile cytoskeletal components were thought to be important for morphological changes of the cells and the gel contraction. In order to examine the relationship between the cytoskeletal components and morphological changes of the cells and gel contraction, colchicine and cytochalasin B, known to be inhibitors for microtubules and microfilaments respectively, were added to the gels and the culture media. Bovine lens epithelia were cultured in the gels and the media containing 0-1000 nM colchicine or 0-10 microM cytochalasin B. Both inhibitors arrested the elongation of the cells and the contraction of the gels. These results suggested that the cell movement caused by the functions of microtubules and microfilaments were related to the vitreous contraction.

Animals↗

PubMed2000

God's organism? The chick as a model system for memory studies.

The young chick is a powerful model system in which to study the biochemical and morphological processes underlying memory formation. Training chicks on a one trial passive avoidance task results in a molecular cascade in a specific brain region, the intermediate medial hyperstriatum ventrale. This cascade is initiated by glutamate release and engages a series of synaptic transients including increased calcium flux, up-regulation of NMDA-glutamate receptors, membrane protein phosphorylations, and the retrograde messenger NO. Expression of immediate early genes c-fos and c-jun precedes the synthesis, glycosylation, and redistribution, >4 hr downstream, of a number of synaptic membrane proteins, notably NCAM and L1. Other membrane proteins required in the early phase of memory formation include the amyloid precursor protein (APP) and apolipoprotein E. There are concomitant increases in dendritic spine number and changes in synaptic structure. Nonsynaptic factors, including corticosterone and BDNF, can modulate retention of the avoidance response, enhancing the salience of otherwise weakly retained memory. These results are discussed in relation to general concepts of memory formation and the spatio-temporal distribution of the putative memory trace.

Animals↗

PubMed2006

Using the Neuman systems model for best practices.

Human beings with unmet needs related to their health and illnesses are the central focus of the domain of nursing. It is proposed in this column that nurses who conduct their practice from a nursing theory base, while assisting individuals and families to meet their health needs, are more likely to provide comprehensive, individualized care that exemplifies best practices. The Neuman systems model has been widely acclaimed to guide practice, yet specific examples are few in the published literature. The purpose of this column is to present two case studies based upon Neuman systems model; one case is directed toward family care, and the other demonstrates care with an individual. Theory-based exemplars serve as teaching tools for students and practicing nurses. These case studies illustrate how nurses' actions, directed by Neuman's wholistic principles, integrate evidence-based practice and generate high quality care.

Adult↗

PubMed2002

Reactive intermediate formation from the 2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A)-derived cysteine S-conjugate S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine in pyridoxal model systems.

2-(Fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (compound A) is a degradation product of the anesthetic sevoflurane and undergoes cysteine conjugate beta-lyase-dependent bioactivation to nephrotoxic metabolites in rats. The present experiments were designed to identify reactive intermediates formed from S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine, a compound A-derived cysteine S-conjugate, in two pyridoxal model systems, namely Cu2+/pyridoxal and N-dodecylpyridoxal in cetyltrimethylammonium micelles. S-[2-(Fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-L-cysteine was incubated in the model systems with benzyl bromide, pentafluorobenzyl bromide, aniline, and o-phenylenediamine as trapping agents. The products were purified by TLC and identified by 19F and 1H NMR spectroscopy and by GC/MS. In the absence of trapping agents, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid, which have been identified previously in biotransformation studies, were formed. With the chemical models, 2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropanethiolate, the expected first intermediate, was not trapped with benzyl bromide. Rather, the dehydrofluorination product 2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenylthiolate was trapped with benzyl bromide to give benzyl 2-(fluoromethoxy)-3,3,3-trifluoropropanethioate, which was formed in both chemical models. When pentafluorobenzyl bromide was used as a trapping agent, GC/MS analysis showed that the expected thiolate was trapped to give pentafluorobenzyl 2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl sulfide in the N-dodecylpyridoxal model. In both chemical models, 2-(fluoromethoxy)-3,3,3-trifluorothioacyl fluoride was trapped with aniline to give N-phenyl 2-(fluoromethoxyl)-3,3,3-trifluoropropanethioamide, which cyclized to give 3-phenyl-4-thiono-5-(trifluoromethyl)-1,3-oxazolane. The results demonstrate that most of the reactive intermediates and products formed by the beta-lyase-catalyzed biotransformation of compound A-derived cysteine S-conjugates are also formed in the two chemical systems studied. Some products were, however, formed in chemical systems that have not been observed in previous in vivo and in vitro studies; it is not known whether these products are formed in biological systems and whether they contribute to the observed nephrotoxicity of cysteine S-conjugates.

Anesthetics, Inhalation↗

PubMed1983

Influence of hypoxia on the metabolism and excretion of misonidazole by the isolated perfused rat liver--a model system.

The isolated perfused rat liver was evaluated as a model system for the characterization of misonidazole metabolism under hypoxic conditions. Misonidazole metabolism by livers perfused under aerobic conditions was also examined. The clearance of misonidazole was more than three times greater under anaerobic compared to aerobic conditions (4.94 +/- 1.56 vs 1.27 +/- 0.22 ml/min; means +/- S.D., N = 3). Misonidazole metabolites were detected only in the bile. Analysis of these metabolites by reverse-phase high performance liquid chromatography (HPLC) demonstrated that misonidazole metabolism was also qualitatively changed when anaerobic conditions were employed. Misonidazole beta-glucuronide was the major metabolite detected under aerobic conditions, but it was a minor metabolite in anaerobically perfused livers. The three major metabolites produced under anaerobic conditions were not characterized, but desmethyl misonidazole (RO-07-9963) and the 2-amino-imidazole derivative of misonidazole (1-[2-aminoimidazol-1-yl]-3-methoxy-2-propanol) were excluded as possible structures.

Animals↗

PubMed1985

Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones: a model system for study of higher order structure.

We describe a model system for study of chromatin structure at levels above that of the nucleosome. A series of fragments with lengths ranging from 172 to 207 bp tandemly repeated three to greater than 50 times was prepared; each repeat contains the region important in forming a positioned core particle on a sea urchin 5S rRNA gene upon in vitro association with histones. The tandemly repeated sequences can be studied as linear DNA fragments or as relaxed or supercoiled circular molecules. A number of criteria indicate that nucleosomes position correctly on all the tandemly repeated elements. Measurement of the change in linking number per core particle led to a value of -1.0. Both length and repeat number dependent changes in conformation of the nucleoproteins are observed. We discuss the possibility that some ordered higher level chromatin structure can form with DNA and core histones alone.

Animals↗

PubMed2005

A dynamical system model of neurofilament transport in axons.

We develop a dynamical system model for the transport of neurofilaments in axons, inspired by Brown's "stop-and-go" model for slow axonal transport. We use fast/slow time-scale arguments to lower the number of relevant parameters in our model. Then, we use experimental data of Wang and Brown to estimate all but one parameter. We show that we can choose this last remaining parameter such that the results of our model agree with pulse-labeling experiments from three different nerve cell types, and also agree with stochastic simulation results.

Animals↗

PubMed2004

Flavor release measurement from gum model system.

Flavor release from a mint-flavored chewing gum model system was measured by atmospheric pressure chemical ionization mass spectroscopy (APCI-MS) and sensory time-intensity (TI). A data analysis method for handling the individual curves from both methods is presented. The APCI-MS data are ratio-scaled using the signal from acetone in the breath of subjects. Next, APCI-MS and sensory TI curves are smoothed by low-pass filtering. Principal component analysis of the individual curves is used to display graphically the product differentiation by APCI-MS or TI signals. It is shown that differences in gum composition can be measured by both instrumental and sensory techniques, providing comparable information. The peppermint oil level (0.5-2% w/w) in the gum influenced both the retronasal concentration and the perceived peppermint flavor. The sweeteners' (sorbitol or xylitol) effect is less apparent. Sensory adaptation and sensitivity differences of human perception versus APCI-MS detection might explain the divergence between the two dynamic measurement methods.

Chewing Gum↗

PubMed2004

A Bohmian total potential view to quantum effects. I. Methodology and simple model systems.

The coherent-state wave packet dynamics of several model systems is analyzed in terms of Bohm's total potential. The quantum dynamics has been obtained by solving the time-dependent Schrodinger equation, and a method for obtaining the total potential from it, involving just matrix algebra, has been proposed. Contrary to what one may expect, it is shown that the time- and state-dependent features of the total potential admit a rationale, classical-like description of quantum effects, leading to a unified picture of them, which is not critically dependent, as for the key features, on the classical potential. An outstanding feature is found to be the relation of the state system's density amplitude and sharpness (in its dependence with position) with quantum effects. Sharp density profiles and low densities cause the total potential to strongly depart from the classical value, in both time regimes and position ranges, which provide a clearer, more deterministic view to quantum dynamics. Free motion as well as scattering processes by square and Eckart barriers have been analyzed by means of careful inspection of several time dependent snapshots. The result is an insightful picture of processes involving tunneling and antitunneling, including their dynamical variants, as well as resonances and quantization.

Journal Article↗

PubMed1985

Noradrenergic modulation of sensorimotor processes in intact rats: the masseteric reflex as a model system.

The masseteric jaw closure reflex was utilized as a model system with which to gauge the functional activity of central noradrenergic neurons. This system was chosen because it is a simple monosynaptic reflex the neuronal substrate of which receives a dense noradrenergic input. The modulatory effects of norepinephrine (NE) on this response in the intact, chloral hydrate-anesthetized rat were studied with a variety of pharmacological strategies. Initially, a reflex facilitation was obtained with the catecholamine precursor L-DOPA. Manipulations with greater specificity of action on the noradrenergic system were then employed. First, we used the presynaptic alpha-2 noradrenergic agonist clonidine, which acts to decrease noradrenergic transmission. Clonidine attenuated the amplitude of the reflex, and this suppression was blocked by pretreatment with the alpha-2 antagonist yohimbine. The effects of yohimbine itself were then examined, and a biphasic effect was obtained. At low doses, at which it preferentially acts as an antagonist at presynaptic alpha-2 receptors and increases noradrenergic transmission, yohimbine enhanced the reflex. At higher doses, at which it also displays postsynaptic alpha-1 antagonist activity, yohimbine depressed the reflex. This reflex modulation by yohimbine was blocked by pretreatment with the alpha-1 antagonist prazosin. The anatomical site of the observed effect was then localized to the direct noradrenergic innervation of the reflex circuitry by locally destroying, with 6-hydroxydopamine, the noradrenergic terminals in the trigeminal motor nucleus mediating the response. This significantly attenuated the reflex modulation by yohimbine, without affecting elicitation of the reflex itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Development of laboratory and animal model systems for HIV-1 encephalitis and its associated dementia.

The neuropathogenesis of HIV-1 encephalitis and its associated dementia revolves around sustained viral replication in cells of mononuclear phagocyte origin (brain macrophages, multinucleated giant cells, and microglia). Macrophage secretory factors play important roles in facilitating monocyte trafficking into the brain, in regulating productive viral replication, and in producing neurotoxic responses. To study these events, we constructed an artificial blood-brain barrier (BBB) to assay monocyte transendothelial migration and developed an animal model system for HIV-1 encephalitis to ascertain the role that virus-infected mononuclear phagocytes play in disease pathogenesis. The BBB model was composed of brain microvascular endothelial cells and astrocytes placed on opposite sides of a porous membrane. Monocyte activation, not HIV-1 infection per se, was the central event affecting monocyte BBB migration. Many of the pathological features of HIV-1 encephalitis were reproduced in SCID mice stereotactically inoculated with virus-infected monocytes. These included widespread astrogliosis, apoptosis of neurons, dendritic damage, and macrophage/microglial activation. Such laboratory and animal model systems are being used to ascertain the pathogenic potential of virus-infected macrophages in brain and ways to curb such injurious effects.

AIDS Dementia Complex↗

PubMed2006

An in vitro model system to study the damaging effects of prolonged mechanical loading of the epidermis.

Pressure ulcers are areas of soft tissue breakdown that result from sustained mechanical loading of the skin and underlying tissues. Today, little is known with respect to the aetiology of these ulcers. This study introduces an in vitro model system to study the effects of clinically relevant loading regimes on damage progression in the epidermis, the uppermost skin layer. Engineered epidermal equivalents (EpiDerm) were subjected to 6.7 and 13.3 kPa for either 2 or 20 h using a custom-built loading device. Tissue damage was assessed by (1) histological examination, (2) tissue viability evaluation, and (3) by the release of a pro-inflammatory mediator, interleukin-1alpha (IL-1alpha). Loading the EpiDerm samples for 2 h increased the IL-1alpha release, although no visible tissue damage was observed. However, in the 20 h loading experiments visible tissue damage and a small decrease in tissue viability were observed. Furthermore, in these experiments the IL-1alpha release increased with magnitude of loading. It is concluded that this in vitro model system can be applied to improve insight in the epidermal damage process due to prolonged mechanical loading and can serve as a sound basis for effective clinical identification and prevention of pressure ulcers.

Epidermis↗

PubMed1986

Effect of induced field inhomogeneity on transverse proton NMR relaxation in tissue water and model systems.

The effect of induced field inhomogeneity (IFI) on transverse NMR relaxation of water protons in tissue has been investigated by examining the field dependence of the effective transverse relaxation rates (1/T2 eff) for in vitro canine brain tissue samples. At fields of 0.47, 2.35, 7.05 T (corresponding to 20, 100, and 300 MHz, respectively) the transverse relaxation rates for both white and gray matter samples follow a field dependence of the form 1/T2 eff = C0 + C1 B0, where B0 is the applied field. The linearly dependent term, C1 B0, which reflects the IFI contribution, does not contribute much (i.e., less than 20%) at fields less than 2.0 T. However, at greater field strengths the contribution is appreciable, e.g., greater than 60% at 7.0 T. Results from model systems of glass beads are also reported to illustrate IFI effects. For both the model systems and canine brain tissue samples, the effects of restricted diffusion are qualitatively evident in Hahn spin-echo experiments.

Animals↗

PubMed2005

Drosophila: a "model" model system to study neurodegeneration.

The fruit fly, Drosophila melanogaster, is a powerful model genetic organism that has been used since the turn of the previous century in the study of complex biological problems. In the last decade, numerous researchers have focused their attention on understanding neurodegenerative diseases by utilizing this model system. Numerous Drosophila mutants have been isolated that profoundly affect neural viability and integrity of the nervous system with age. Additionally, many transgenic strains have been developed as models of human disease conditions. We review the existing Drosophila neurodegenerative mutants and transgenic disease models, and discuss the role of the fruit fly in therapeutic development for neurodegenerative diseases.

Animals↗

PubMed1997

P19 embryonal carcinoma cells: a model system for studying neural tube induction of skeletal myogenesis.

A model experimental system for investigating myogenic induction signals has been devised with mouse P19 embryonal carcinoma cells. When cocultured with pieces of chick neural tube, aggregated P19 cells are induced to become skeletal muscle. The most potent inducing activity is localized to the dorsal neural tube. Less activity was found in the ventral neural tube, notochord, ectoderm, and lateral plate mesoderm, and none was detected in the neural retina. These results suggest that P19 cells may be a useful model system for investigating the mechanisms underlying induction of somite myogenesis.

Animals↗

PubMed2003

[In vitro model system of transepithelial migration of neutrophil by Helicobacter pylori].

BACKGROUND/AIMS: Migration of neutrophil across the intestinal epithelium is a structural hallmark of active intestinal diseases. One of the characteristic histologic features of Helicobacter pylori (H. pylori) infection is neutrophil infiltration of the gastric mucosa. This study was aimed to establish an in vitro model system of transepithelial migration of neutrophil by H. pylori. METHODS: Caco-2 cells were grown on polycarbonate membrane. Confluence and integrity were assessed by measuring the transepithelial electrical resistance (TER) and paracellular permeability of macromolecular marker. IL-8 mRNA expression was assessed after H. pylori infection by quantitative RT-PCR. Isolated neutrophils and H. pylori were applied to the basolateral and apical compartment in separate. Also neutrophil transmigration was assessed by light and electron microscopy. RESULTS: Paracellular leakage of 3[H]-mannitol was negligible over TER 166 Omega x cm2. IL-8 mRNA expression increased after H. pylori infection. Neutrophil transmigration was increased by adding of N-formyl-methionyl-leucyl-phenylalanine or H. pylori. CONCLUSIONS: This in vitro model system could be applied to the study of pathogenesis of H. pylori infection. A further study of quantification of transmigrated neutrophils is demanded to reach a confirmation.

Caco-2 Cells↗

PubMed2004

Optical characteristics of thiamine in model systems and in holoenzyme.

The optical properties of thiamine diphosphate-dependent enzymes change significantly on their interaction with cofactors (thiamine, bivalent metal ions) and substrates. These changes are connected with structural alterations of the active site and the mechanism of its functioning, and in some cases they reflect changes in the optical properties of the coenzyme itself within the protein. The use of optical characteristics, especially together with model systems, appeared to be a rather promising approach for investigation of the active site of thiamine diphosphate-dependent enzymes and the mechanism of its functioning. So, it seemed to be useful to summarize the literature data concerning the optical characteristics of thiamine (thiamine diphosphate) in model systems and the efficiency of their application for study of thiamine diphosphate-dependent enzymes.

Circular Dichroism↗

PubMed1995

Melanoma formation in Xiphophorus: a model system for the role of receptor tyrosine kinases in tumorigenesis.

Cancer is one of the most frequent fatal human diseases. It is a genetic disease, and molecular analysis of the genes involved revealed that they belong to several distinct classes of molecules, one of which is the receptor tyrosine kinases. Neoplastic transformation is regarded as the result of a multistep process and, in most cases, it is hard to evaluate what the initial events in tumor formation are. What makes it difficult to approach this question is the paucity of animals models for tumorigenesis allowing investigation of the mechanisms leading to uncontrolled cell proliferation. Melanoma formation in Xiphophorus is one of these model systems. Here, overexpression and activation of a receptor tyrosine kinase causes neoplastic transformation of pigment cells. Xiphophorus provides all the advantages of a well-characterized genetic system. In addition, some crucial components of the transformation pathway have been identified at the molecular level. As a vertebrate, Xiphophorus might serve as a model system to aid understanding, in more general terms, of the mechanisms of tumorigenesis in human diseases.

Animals↗