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Interaction of the peptide hormone adrenocorticotropin, ACTH(1-24), with a membrane model system: a fluorescence study.

The peptide hormone adrenocorticotropin and a related peptide were studied in solution and in interaction with a model system of membranes (small unilamellar vesicles of dipalmitoylphosphatidylcholine and 17% dimyristoylphosphatidylglycerol) via fluorescence spectroscopy. In aqueous solution, intramolecular distances between the fluorescent residues R(Tyr2-Trp9) = 9.2 A and R(Trp9-Tyr23) > or = 18 A were obtained, in agreement with molecular models. Interaction of the peptide with the negatively charged membrane is evident from the alteration of the Trp photophysical parameters (quantum yield, fluorescence spectra and anisotropy), with a partition constant between the lipidic and aqueous phase of Kp = 1-2 x 10(3). The existence of two populations of Trp in the membrane, which are distinctly accessed by acrylamide, was concluded from the tryptophan fluorescence quenching study; the two fractions are located near the membrane interface as inferred from its fluorescence quenching by the 5-doxylstearate and 16-doxylstearate lipophilic quenchers. This result is further supported by energy transfer experiments to the 3-(9-anthroyloxyl)stearic acid and 12-(9-anthroyloxyl)stearic acid probes.

1,2-Dipalmitoylphosphatidylcholine↗

A model system for testing gene vectors using murine tumor cells on the chorioallantoic membrane of the chick embryo.

We developed a model system for testing gene vectors, based on the growth of murine tumors on the chorioallantoic membrane (CAM) of embryonic chickens. The ability of selected murine cells to grow on the CAM was rated according to the following criteria: i) formation of tumor masses; ii) metastasis formation; iii) reproducibility; iv) yield, indicated as the number of embryos surviving to assessment time with visible tumors on the CAM; v) maintainability of the cell, both in the original host and the embryonic chick, or 'shuttle maintainability'; vi) detection by the naked eye, and vii) cost/benefit relation. The murine melanoma cell lineage, B16F10, which efficiently forms distinct, pigmented tumor masses and metastases on the CAM, performed better in this model than the murine B61 cell line. In vitro transduction of B16F10 cells with a recombinant adenovirus carrying a construct of the E. coli LacZ gene followed by inoculation onto the CAM resulted in beta-galactosidase expression in the tumor mass growing on the CAM. This model is potentially applicable to preclinical evaluation of gene vectors, especially for gene therapy of cancer.

Adenoviridae↗

The role of aminochromes in ultraweak luminescence accompanying oxidative metabolism of catecholamines in model systems in vitro.

Ultraweak luminescence (UWL) accompanying oxidative transformations of catecholamines (CA) into melanins, particularly adrenaline and noradrenaline in the model system CA + Fe(CN)6(3-) + OH(-) + H2O2 in vitro was investigated by spectroscopic methods. Separate steps of the oxidative transformations from CA to melanins were analyzed with respect to their energetic/spectroscopic properties in order to evaluate the possibility of chemiexcitation and light emission. Results of experiments with pure adrenochrome + H2O2 + OH- provided evidence pointing to the key role of the interaction between aminochromes and active oxygen species.

Adrenochrome↗

Model systems for flavoenzyme activity: site-isolated redox behavior in flavin-functionalized random polystyrene copolymers.

[reaction: see text] A model system has been developed to study the redox behaviors of flavin derivatives appended onto random polystyrene copolymers through "click" chemistry strategies. The results demonstrate that flavin units attached onto polymers exhibit site-isolated redox behaviors, yielding new materials with electrochemically tunable associations (K(a)(ox) = 450 M(-)(1), K(a)(red) = 18,200 M(-)(1)) to complementary diamidopyridine (DAP) functionality.

Electrochemistry↗

Lactic acid bacteria: model systems for in vivo studies of sugar transport and metabolism in gram-positive organisms.

Lactic acid bacteria provide a model system for the in vivo study of mechanisms pertaining to the regulation of sugar transport and metabolism by microorganisms. Recent studies with resting and growing cells of the homofermentative Streptococci and Lactobacilli have yielded evidence for hitherto unsuspected regulatory mechanisms in this group of industrial and medically important bacteria. These regulatory mechanisms mediate the exclusion and expulsion of sugars, the preferential transport of sugar from sugar mixtures, resistance to non-metabolizable sugar analogs and participate in the establishment of energy-dissipating futile cycles. Transport experiments conducted with novel sugar analogs, data from enzymatic analyses and 31P-NMR spectroscopy studies with wild type and mutant strains of Streptococci, have provided new insight into the fine- and coarse-controls responsible for the modulation of activity of the sugar transport: glycolysis cycle. The purpose of this review is to summarize our current knowledge of these regulatory mechanisms and to suggest avenues for future investigation. Although specifically addressed to the lactic acid bacteria, it seems likely that some of the mechanisms described will be found in other Gram-positive species.

Biological Transport↗

Model systems for cardiotoxic effects of anthracyclines.

The use of anthracycline antibiotics in cancer chemotherapy is limited by their cardiotoxic qualities. For the evaluation of new derivatives animal model systems are required. Cardiomyopathy can be induced in rabbits and monkeys, but these models are too expensive for screening purposes. In rats, anthracycline antibiotics cause morphologic lesions of the heart muscle, but these are more difficult to demonstrate than in larger animals. However, significant changes of the heart function (electrocardiogram (ECG), cardiac output), the function of heart mitochondria (inhibition of electron transfer, uncoupling of oxidative phosphorylation and inhibition of Ca translocation) occur in a dose-related manner. Intraventricular conduction defect demonstrated in the ECG is one of the earliest and most consistent expressions of the cardiotoxic properties of anthracyclines. It was therefore used as primary screening parameter. The results of the screening of over 50 new anthracyclines has shown that the cardiotoxic properties vary considerably and that they are not closely related to the chemotherapeutic and the hematotoxic properties. Interesting structure-activity relationships were observed in a series of rubidazone derivatives substituted at the benzhydrazone part of the molecule.

Animals↗

Model systems in neurooncology.

Cell- and molecular biological techniques have had a major impact on experimental neurooncology in recent years; yet we are lacking suitable model systems. Monolayer cell cultures are rapid, reproducible and reliable systems, however, their validity is of major concern. Three dimensional culture systems, especially derived from primary biopsies, match better with the in vivo situation albeit being more tricky to handle. Animal models for glioma have to be orthotopic in order to draw any conclusions; most cell lines implanted into rodents still do not show the typical invasive phenotype. In addition, immunological phenomena have to be taken into account as well as changes of the biological features once cells have undergone the process of any transfection.

Animals↗

The rabbit retina: a long-term model system for aluminum-induced neurofibrillary degeneration.

Aluminum (Al) was injected into the rabbit eye as a potential long-term model system for Al-induced neurofibrillary degeneration (NFD). Neurofibrillary tangles made up of 10 nm phosphorylated neurofilaments were observed in a subpopulation of retinal ganglion cells, located primarily in the peripheral retina. The distribution of affected cells suggested a differential susceptibility of ganglion cells to Al intoxication. Importantly, none of the animals demonstrated any of the central neurological dysfunctions characteristic of previous Al intoxication models. The retinal model should allow for long-term studies of Al intoxication and its potential relationship to neurofibrillary degenerative disorders such as Alzheimer's disease.

Aluminum↗

A physical characterization of biological information and communication system model of ecosystems.

What is information for living organisms? An answer to this question is given on a physical basis and a contrast between genetic information and sensory information is stressed with a relation to information theory. A simple model of an environment of living organisms is investigated on the basis of communication systems model proposed by the author and a cost of information transmission is taken into consideration through capacity cost theory. It is shown that channel capacity of information theory can be interpreted as an environment, and furthermore that a large diversity of genetic messages needs a large capacity of the environment. In addition, a definition of life in terms of information is proposed and a unified view on life processes is suggested.

Animals↗

Formation of the mutagen IFP in model systems and detection in restaurant meats.

Mixtures of the free amino acids, creatine and glucose, were dry-heated to model the potential formation of heterocyclic amines in meats. The formation of the mutagenic amine IFP (determined to be 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine) was investigated by varying heating time, heating temperature, and precursors. With an optimized mixture of glutamine, creatine, and glucose, heated at 200 degrees C for 60 min, 2 mg of IFP was purified for studies to define its structure. Trideuteriomethyl-IFP was made from trideuteriomethylcreatinine in the model system for use in LC-MS detection of IFP in foods. Analysis of well-done meats purchased from restaurants showed about half to contain IFP at levels from 1.4 to 46 ng/g of cooked meat, demonstrating human exposure to this mutagen.

Cooking↗

Neuman systems model used as a guide for the nursing care of an 8-year-old child with leukemia.

The Neuman Systems Model (NSM) provides a framework for holistic pediatric oncology nursing practice. In this article, an overview of NSM is given. This model is applied to an 8-year-old child with leukemia for the comprehensive assessment, planning, and evaluation of nursing care. A comprehensive list of nursing diagnoses is categorized by primary and secondary prevention.

Antineoplastic Combined Chemotherapy Protocols↗

A rabbit bone marrow model system for evaluation of cytotoxicity: characterization of normal bone marrow cell cycle parameters by flow cytometry.

Characterization of a rabbit model system for the study of cell cycle effects of myelotoxic agents in normal bone marrow is described. Cell cycle phase distributions are obtained by computer analysis of flow cytometric single cell DNA histograms. Comparison of marrow aspirates with marrow samples from sacrificed animals indicates that dilution of aspirates with peripheral blood is not significant. Aspiration of marrow from one bone does not affect the cell cycle distribution of unsampled bones. Hence, sequential aspirates of different bones in a single animal may be used as representative samples for further study of effects of myelotoxins on marrow proliferation and differentiation.

Animals↗

The Torpedo electrocyte: a model system for the study of receptor-cytoskeleton interactions.

We have used the electrocyte of Torpedo electric organ as a model system for the study of AchR stabilization in the postsynaptic membrane. Attention was focused on membrane cytoskeleton interactions in particular on a peripheral protein of 43 KD that is believed to participate in AchR immobilization. Using immunocytochemical methods, we have shown that the cortical skeleton in Torpedo electrocyte displays a local differentiation proper for each specialized domain of the plasma membrane. In the postsynaptic membrane, characterized by an accumulation and a geometrical organization of the receptors in the plane of the membrane, the 43 KD protein participates in a submembraneous coating or "postsynaptic densities" that strictly codistribute with the AchR. The 43 KD protein might also account for the anchoring of intermediate-sized filaments. The organization of the postsynaptic domain appears readily different from that of the non-innervated one where the membrane folds are maintained by a cortical meshwork of cytoskeletal proteins such as ankyrin, spectrin and oligomeric actin. In conclusion, the asymmetrical organization of the cortical skeleton in the electrocyte offers a unique opportunity for the study of the specific aspects of membrane-skeleton interactions that take place in the postsynaptic domain.

Acetylcholine↗

Fetal alcohol syndrome: early olfactory learning as a model system to study neurobehavioral deficits.

The goal of basic research examining the deficits underlying fetal alcohol syndrome is to develop an animal model which allows investigation and assessment of the neural and cognitive impairments resulting from prenatal alcohol exposure. The following review focuses on animal models and their relationship to human deficits following prenatal alcohol exposure. In addition, this review examines a unique, well-established model system which may permit an increased understanding of the role of alcohol on the developing brain and cognitive behavior. Specifically, large metabolic, neurochemical, neuropharmacological, morphological and neurophysiological changes in young rats have been reported as a consequence of early olfactory preference conditioning, a form of learning that normally occurs during both human and rat development. This olfactory odor preference training paradigm can be used to assess changes in learning as well as the neural substrates underlying this learning. Olfactory preference training has been used to examine: 1) learning, as demonstrated by a behavioral preference for an odor previously paired with stimulation which mimics maternal care; 2) metabolism, by measuring 2-deoxyglucose uptake and distribution in response to the trained odor; 3) neurotransmitter levels, by using in vivo microdialysis, to examine changes in neurotransmitter levels in the olfactory bulb in response to a trained odor. Using in vivo microdialysis enables measurement of both baseline responsiveness of alcohol-exposed pups as well as learned responses at several different developmental ages. The established neural features of this olfactory model include an increase in behavioral preference for a trained odor, increases in 2-DG uptake in specific foci within the olfactory bulb in response to the odor, and increases in dopamine in response to olfactory preference training stimuli, as well as conditioned increases in norepinephrine following olfactory preference training. Using these known behavioral, metabolic and neurochemical indices in control pups allows identification of some of the neurotransmitter systems involved in deficits and the neurobiological basis for impairments induced by prenatal alcohol exposure.

Animals↗

Attempt to disturb receptor memory in a unicellular (Tetrahymena) model system.

The effect of a hormone-like substance first reaching a receptor is of decisive importance in the unicellular (Tetrahymena) model system. The effect of the similar or dissimilar molecule after the first or second pretreatment depends to a great extent on pretreatment if it was carried out by a similar substance, but it does not depend on it if the agent used for pretreatment was different chemically. Receptor memory developing after hormonal imprinting can thus be disturbed by molecules of similar nature, but the effect of a different molecule--if it acts immediately after the imprinting--cannot be neglected, either.

Alkaloids↗

Does quantitative tRNA adaptation to codon content in mRNA optimize the ribosomal translation efficiency? Proposal for a translation system model.

Neither a dynamic nor an energetic approach of the translation process has taken into account that intracellular levels of iso-tRNA species are adapted or adjusted to the codon frequency of mRNA being decoded (Bombyx mori silk gland, rabbit reticulocyte). A critical study of available experimental data suggests that the average elongation rate of a protein is maximized in the presence of an adapted tRNA population, usually an homologous tRNA. In addition, the amount of synthesized protein parallels that of corresponding mRNA. Other evidences--including in vitro and in vivo elongation assays with fibroin mRNA--show that individual elongation rates are not uniform. Pauses occur at certain sites of the mRNA chain. The relative lifetime of these pauses depends on the tRNA pool used. Finally, it appears that translation accuracy also depends on the balanced tRNA population. We propose to explain these different effects by using a codon-anticodon recognition model, called "trial and error system" based on a stochastic processing of the ribosome. Accordingly, various acylated tRNA species which surround a ribosome randomly encounter the receptor A site. Every trapped tRNA species is tested for a proper pairing with the codon to be recognized at the level of a comparator or discriminator function. If the pairing is correct, transpeptidation becomes irreversible. If not, the aminoacyl-tRNA is rejected and another randomly trapped tRNA is processed in turn. Mathematical analysis of this model shows that the mean number of trials used for translating the whole sequence of a mRNA is minimized when the proportion of different iso-tRNA species is correlated with the square root of codon frequency. Quantitations of reticulocyte tRNA support such a parabolic relation. Our translation system model brings some light into the role of tRNA adaptation for optimizing translation efficiency, i.e. maximizing both speed and accuracy. Some consequences of the model are discussed.

Codon↗

Immunomagnetic colloids for the enrichment of tumor cells from peripheral blood and bone marrow: a model system.

The characterization of tumor cells in bone marrow harvested for autologous bone marrow rescue remains a problem due to the limited sensitivities of the techniques available for their analysis. This complicates the use of purging techniques as their usefulness is debated, specifically because it is not known if they can remove all residual tumor cells from either peripheral blood stem cell harvests or bone marrow. Apart from developing more sensitive techniques for tumor detection, one way of increasing our efficiency at identifying rare malignant cells in normal hematopoietic cells is to develop approaches to enrich the population of interest prior to analysis. Here, we describe a laboratory-based system for tumour enrichment employing panels of monoclonal antibodies (MAbs) and an immunomagnetic colloid. In model systems, tumor cells could be enriched approximately 100-fold with high yield and purity. The adaptations of this technology to permit further cell enrichment and the choice of either an immunological technique or a molecular approach to tumor identification are discussed in detail.

Bone Marrow↗

A systemic model of the youth mentoring intervention.

Conceptual and empirical work on youth mentoring naturally tends to focus on the relationship between mentor and child. However, the parent/guardian and agency caseworker also may contribute to the success or failure of the mentoring intervention, and program effects may be partially mediated by the child's interactions with these individuals. This article presents a systemic model of mentoring depicting the interdependent network of relationships established between mentor, child, parent/guardian, and caseworker against the backdrop of agency policies and procedures. Numerous examples illustrate pathways of influence and patterns of communication in the context of this more holistic model of mentoring. Editors' Strategic Implications: Drawing upon ecological and systems theories, the author provides a promising conceptual model that focuses on patterns of interpersonal exchange among several key individuals (but not the only possible ones). This model reminds researchers and practitioners that mentoring resides within a mutually reinforcing (or inhibiting) network of other relationships. This systemic thinking has implications for child welfare agency policies and practices.

Adolescent↗