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PubMed2002

High pressure-induced changes of biological membrane. Study on the membrane-bound Na(+)/K(+)-ATPase as a model system.

In order to study the pressure-induced changes of biological membrane, hydrostatic pressures of from 0.1 to 400 MPa were applied to membrane-bound Na(+)/K(+)-ATPase from pig kidney as a model system of protein and lipid membrane. The activity showed at least a three-step change induced by pressures of 0.1-100 MPa, 100-220 MPa, and 220 MPa or higher. At pressures of 100 MPa or lower a decrease in the fluidity of lipid bilayer and a reversible conformational change in transmembrane protein is induced, leading to the functional disorder of membrane-associated ATPase activity. A pressure of 100-220 MPa causes a reversible phase transition in parts of the lipid bilayer from the liquid crystalline to the gel phase and the dissociation of and/or conformational changes in the protein subunits. These changes could cause a separation of the interface between alpha and beta subunits and between protein and the lipid bilayer to create transmembrane tunnels at the interface. Tunnels would be filled with water from the aqueous environment and take up tritiated water. A pressure of 220 MPa or higher irreversibly destroys and fragments the gross membrane structure, due to protein unfolding and interface separation, which is amplified by the increased pressure. These findings provide an explanation for the high pressure-induced membrane-damage to subcellular organelles.

Adenosine Triphosphatases↗

PubMed1968

Food-borne virus:detection in a model system.

The purpose of this study was to develop methods for detection and quantitation of food-borne virus. Samples (25 g) of cottage cheese, contaminated with various quantities of coxsackievirus type A9, comprised the model system. Two of the methods presented have at least a 50% probability of detecting virus at levels below 5 plaque-forming units/25-g sample. Noteworthy aspects of these methods include use of a glycine-NaOH buffer (pH 8.8) containing approximately 1 m MgCl(2) as the diluent in which the sample is slurried, treatment of the slurry with Freon TF and bentonite to facilitate centrifuge clarification, and concentration of the clarified sample extract by a two-stage process employing polyethylene glycol followed by ultracentrifugation. Virus in the final 0.5-ml sample concentrate was detected and quantitated by the plaque technique in rhesus monkey kidney cell cultures. Processing of the sample requires approximately 2 days, and the inoculated cultures may have to be observed for as long as 7 days thereafter. If these levels of sensitivity are desired, and if 12 samples per day are tested on a routine basis, the cost savings achieved by employing these methods rather than testing sample extracts without concentration may range from 75 to 90%.

Buffers↗

PubMed1997

Amyotrophic lateral sclerosis and Alzheimer disease. Lessons from model systems.

The human neurodegenerative diseases, including motor neuron disease and Alzheimer's disease (AD), are characterized by a selective involvement of certain regions of the brain/spinal cord and selected populations of neurons. Sporadic amyotrophic lateral sclerosis (ALS) is an age-associated disease with cytoskeletal abnormalities and death of motor neurons; familial ALS (FALS), an autosomal dominant disease linked to mutations in superoxide dismutase 1 (SOD1), is manifested by inclusions and degeneration of motor neurons. Autosomal dominant familial AD (FAD), linked to mutations in presenilin (PS1 and PS2) genes or the amyloid precursor protein (APP) gene, shows brain abnormalities (e.g., neurofibrillary tangles, deposits of .-amyloid A., and death of subsets of neurons) similar to those that occur in sporadic AD, the risk of which is enhanced by the presence of one or two copies of apolipoprotein E4 (apoE4) alleles. To examine the mechanisms of these diseases, investigators have used a variety of animal models, including experimentally produced, spontaneously occurring, or genetically engineered models of disease. Studies of models of degeneration of motor neurons (axotomy) and cytoskeletal abnormalities seen in motor neuron disease (i.e., axonopathy induced by .,.'-iminodipropionitrile (IDPN), hereditary canine spinal muscular atrophy (HCSMA), and neurofilament NF transgenic Tg mice) have demonstrated that NF-filled swellings of axons are related to alterations in the biology of NF transport. Tg mice with SOD1 mutations, which develop the clinical features of FALS, show selective degeneration of motor neurons, which is attributed to the acquisition of toxic properties by mutant SOD1. Models of AD include: aged monkeys that show both cognitive/memory deficits and cellular abnormalities (amyloid deposition/cytoskeletal abnormalities of neurons) in cortex and hippocampus; and Tg mice that express mutant human FAD-linked genes (i.e., APP and PS1) and show increased levels of A.42, amyloid deposits, dystrophic neurites, and local responses of astrocytes and microglia. This review discusses the behavioral/neuropathological features of AD, the results of investigations of mechanisms of disease in model systems, and potential utility of some of these models for testing new therapies.

Alzheimer Disease↗

PubMed1998

HIV type 1 infection in lymphoid tissue: natural history and model systems.

The pathogenesis of human immunodeficiency virus (HIV) in the lymphoid compartment has a dramatic effect on disease progression and important implications for therapeutic and vaccine strategies. Here we discuss current understanding of the pathogenesis of HIV in the lymphoid tissue. Various model systems that allow examination of the effect of retroviral infection in primary lymphoid organs are discussed, as well as current progress made with the use of these systems, with particular emphasis on the SCID-hu mouse.

Animals↗

PubMed1994

The leg of Drosophila as a model system for the analysis of neuronal diversity.

The neurons innervating insect sense organs vary in number, shape, dendritic morphology, axonal projections and connectivity, providing abundant material for the genetic analysis of neuronal diversity. Here we describe the leg of Drosophila as a potential model system for this analysis. The leg of Drosophila comprises a variety of sense organs arranged in a precise and reproducible pattern. The cell bodies of the sensory neurons are located near the organ they innervate, which greatly facilitates their identification and accessibility. The development of the leg from its progenitor structure, the imaginal disc, is known in good detail. In particular, the time of appearance and of divisions of the sense organ precursors is known. The origin and mode of formation of the leg nerve (through which all sensory axons project into the central nervous system) has been described. The central projections of some of the sensory neurons have been examined by horseradish peroxidase backfill or DiI labelling. Finally, the expression of several genes that control the differentiation of various types of sensory neurons can be manipulated at will. We illustrate these different aspects, and discuss the potentials and shortcomings of this system.

Animals↗

PubMed1999

Pattern formation and cell differentiation: trichomes in Arabidopsis as a genetic model system.

Arabidopsis trichomes are single-celled hairs that originate from epidermal cells and are distributed regularly on most aerial body parts. During the last decade, trichome formation in Arabidopsis has been established as a genetic and molecular model system to study various general developmental and cellular mechanisms. This review summarizes progress in the investigation of several aspects of trichome development: the spatial regulation of cell fate determination, the regulation of cell differentiation in response to exogenous signals and plant hormones, and the regulation of endoreplication, cell growth, and cell morphogenesis.

Arabidopsis↗

PubMed2000

Flavor release of diacetyl and 2-heptanone from cream style dressings in three mouth model systems.

The release of volatile compounds from a cream style dressing, which consisted of a thickening agent dispersed in the water phase of an oil in water (o/w) type of emulsion, was studied by the purge-and-trap (PT), dynamic head space mastication (DHM) and dynamic headspace (DH) model systems for diacetyl and 2-heptanone as two volatile compounds. Big differences were detected in the quantity of volatiles released by the three models for both diacetyl and 2-heptanone: PT released the most, followed by DHM and DH. Nitrogen gas bubbling in PT and plunger up-and-down motion in DHM mimic mouth movements and promoted volatile release more than DH. The quantity of volatiles released depended on the nitrogen gas flow rate and isolation period with both the PT and the DHM model. Static headspace measurements indicated that no interaction occurred between the volatiles and the dispersion thickening agent, nor between the volatiles and protein of saliva.

Diacetyl↗

PubMed1972

Spontaneous atherosclerosis in pigeons. A model system for studying metabolic parameters associated with atherogenesis.

The interpretation of metabolic studies related to early changes in spontaneous atherosclerosis has been hampered by the focal nature of the disease and by the lack of a well-defined model system of the disease process. Gross, histologic and ultrastructural observations of lesion development at the celiac bifurcation of the aorta in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons are compared and discussed in terms of hemodynamics, muscular aggregation and altered metabolism of smooth muscle cells. Detailed knowledge of the morphologic sequence of events in lesion localization makes the celiac bifurcation in White Carneau and Show Racer pigeons a useful model for genetic comparisons of arterial wall metabolism and for investigating metabolic alterations occurring with atherogenesis.

Animals↗

PubMed1996

Simulation of the cellular oxygen effect with an SV40 DNA model system using DNA strand breaks as an end point.

Most in vitro studies of the modification of radiation damage to DNA by oxygen and reduced thiol compounds have excluded non-thiol .OH scavengers. However, the non-thiol .OH scavengers are known to be very effective radiation protectors and are present in cells in near molar concentrations. To better relate data obtained from an in vitro system to data at the intracellular level, we have carried out simultaneous measurements of single and double-strand breaks (SSBs and DSBs) in a model system using closed-circular supercoiled SV40 DNA (25 micrograms/ml) in aqueous solution. Observations were made in the presence and absence of oxygen and over wide concentration ranges encompassing intracellular conditions of both glutathione (GSH), the dominant soluble intracellular reduced thiol compound, and glycerol, a widely used poly-alcohol non-thiol .OH scavenger. The dose-response curves for both SSBs and DSBs in either air or nitrogen are predominantly linear when 75 or 750 mM glycerol is combined with 0-20 mM GSH. Glutathione together with glycerol shows a concentration-dependent preferential protection in nitrogen compared to air against radiation-induced SSBs and DSBs, qualitatively similar to our prior observations at comparable concentrations of GSH alone (Ayene et al., Radiat. Res. 144, 1-8, 1995). With GSH alone, we observed peak oxygen enhancement ratios (OERs) of 6.5 and 8.0 for SSBs and DSBs, respectively, at 5 mM GSH. In contrast, we observed previously that glycerol alone showed a preferential protection against radiation-induced SSBs and DSBs in air compared to nitrogen (Ayene et al., Radiat. Res. 142, 133-143, 1995). In the presence of 750 mM glycerol, approximately equivalent to the total effective concentration of non-thiol .OH scavengers in the cell, we now observe that the OER for radiation-induced DSBs increases from 1.2 at 0.5 mM GSH to 3.3 at 5.0 mM. This roughly parallels the dependence of the OER on [GSH] reported for cell survival. A possible mechanism for the lower OER at higher .OH scavenging efficiency is discussed.

DNA Damage↗

PubMed1991

Chemiluminescent nucleic acid detection with digoxigenin-labeled probes: a model system with probes for angiotensin converting enzyme which detect less than one attomole of target DNA.

Digoxigenin-labeled nucleic acid probes for angiotensin-converting enzyme were prepared by the polymerase chain reaction. In a model system, these probes were used to optimize conditions for target detection by direct chemiluminescence after dot-blot, Southern, or Northern hybridizations. Digoxigenin-labeled probes detected 23 fg (1.6 X 10(-19) mol or 9 X 10(4) copies) of target consistently.

Animals↗

PubMed1992

Promoting action of cashew nut shell oil in DMBA-initiated mouse skin tumour model system.

The commercially available oil derived from the shell of cashew nut (Anacardium occidentale) was tested for its potency in promoting the DMBA-initiated cells into papillomas in a murine two-stage skin tumorigenesis model system. Male Swiss albino mice (9-10-weeks-old) were assorted into different groups and treated topically with single sub-carcinogenic doses of DMBA (50 micrograms in 0.1 ml acetone) followed by application of 1% and 2% shell oil in acetone three times a week. Animals were sacrificed after 20 weeks from the commencement of the experiment. The results imply a weak tumour promoting effect of cashew nut shell oil as the mean tumour incidences were found to be 1.1 and 2.5 in 1% and 2% oil treatment groups, respectively, while the corresponding figure vas 6.6 in the positive control group (DMBA and 1% croton oil in acetone). Few speculative mechanisms for the observed effect of cashew nut shell oil on initiated skin are discussed.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Brain injury as a result of violence: preliminary findings from the traumatic brain injury model systems.

OBJECTIVES: To identify possible risk factors that may predispose individuals to violent traumatic brain injury (TBI) and to determine the effect of etiology of injury on outcomes. STUDY DESIGN: Prospective, longitudinal multicenter study. SETTING: TBI Model Systems (TBIMS) located at Wayne State University/Rehabilitation Institute of Michigan, Detroit, MI; The Institute for Rehabilitation and Research, Houston, TX; Medical College of Virginia, Richmond, VA; and Santa Clara Valley Medical Center, San Jose, CA. SUBJECTS: Individuals treated in the four TBIMS programs between 3/89 and 9/96 who met the criteria for inclusion in the TBIMS National Database and for whom the etiology was known (n=812). MAIN OUTCOME MEASURES: Functional Independence Measure, Alcohol Quantity Frequency Variability Index, Community Integration Questionnaire. RESULTS: Individuals who incur violence-related TBI tend to be male, nonwhite, unmarried, living alone, less educated, and unemployed at time of injury. They tend to have less severe brain injuries and better motor function at the time of admission to inpatient rehabilitation. At 1 year postinjury, they score lower on community integration measures; however, no difference exists in functional status. Etiology of injury was found to only play a minor role in the prediction of social and productive integration at 1 year postinjury. CONCLUSIONS: Survivors of violent and nonviolent TBI have similar functional outcomes; however, they differ in preinjury and postinjury socio-economic characteristics, injury severity, and postinjury community integration. Socio-economic factors appear to play a large role in the risk for violent injury and in community integration following injury.

Activities of Daily Living↗

PubMed1999

Diffusion distances of known iron complexes in model systems.

Diffusion distances (abbreviated d's), the distances between the sites of generation of presumed hydroxyl radicals (*OH) by low molecular weight forms of Fe and the site of their reaction with substrate, were measured for three model systems for cellular DNA of varying degrees of complexity. Two d's for Fe complexed with each of ethylene diamminetetraaccetic acid (FeEDTA) and nitrilotriacetic acid (FeNTA) were measured for generation of malondialdehyde-type products (MDA) from deoxyribose and of single-strand breaks (SSBs) in the plasmid pBR322. The closer d's for pBR322 SSB generation (5-6 nm) were considerably greater than the d's for MDA generation in the deoxyribose assay (2-3 nm). This is consistent with charge-charge interactions playing an important role in defining d. The d's for FeNTA, FeEDTA, and other Fe species generating SSBs in isolated Ehrlich ascites tumor cell nuclei ranged from 2.1 to 14 nm. Charge-charge interactions, Fe-ligand-specific interactions, and binding to nuclear components were concluded to be important factors affecting d in isolated nuclei. Other factors related to nuclear structure may also play a role.

Animals↗

PubMed1980

Model system for the study of inital damage to arterial endothelial cells in situ by scanning electron microscopy.

The central artery of the rabbit ear was injected with either 1 ml of control or test solutions in a model system which allowed for the study of effluent fractions coming from a segment of the artery and for the examination of the vessel by electron microscopy. The procedure allowed for either mixing of blood with the test solution ("flow by") or injection of the solutions in the absence of blood ("no flow by"). Effluent fractions were collected and assayed for 6-keto-PGF1 alpha, and indicator of PGI2 production. After the collection of effluent fractions, the artery was perfused with 1% glutaraldehyde to begin fixation. Ultrastructural damage to endothelial cells was seen, by SEM, in a graded response to sodium arachidonate solutions at concentrations between 6.6 and 3.3 mM ("flow by"); and between 3.3 and 0.83 mM ("no flow by"). Lower concentrations of arachidonate did not cause damage. Damage included enucleation, separation or denudation of endothelial cells. Sodium linoleate produced similar damage. A burst of PGI2 production appeared to be associated with arachidonate-damaged endothelium. Injection of sodium arachidonate at lower concentrations (0.33 mM and 0.165 mM) resulted in continuous production of PGI2 over a period of 1 to 5 minutes.

Animals↗

PubMed2003

An in vitro model system to predict the bioaccessibility of heterocyclic amines from a cooked meat matrix.

To understand the impact of variation in digestion parameters on the release of heterocyclic amines naturally formed during cooking, we developed and characterized a model system to assess the effect of amylase, pepsin, and pancreatin on digestion of well-done chicken. The amounts of MeIQx, DiMeIQx, IFP, and PhIP in the liquid portion of the digestate were compared to levels in the undigested meat to determine the percentage released (accessible fraction). Incubating the meat with amylase and pepsin did not change the accessibility of HAs when compared to incubation with water alone. In contrast, increasing amounts of pancreatin increased the accessibility up to 6.4-fold. Comparing the amounts of the HAs in the liquid to the solid fraction showed that there was more MeIQx, DiMeIQx, and IFP in the liquid fraction. In contrast, PhIP was equally divided between the solid and liquid fractions. For all four compounds, increasing the doneness of the meat decreased the amount of the compound accessible from the meat matrix. Our data suggest that bioaccessability of HAs may vary according to the polarity of the individual HAs and also may depend upon the doneness of the meat. These results may have important ramifications for human feeding studies, which assume that the total amount of each HA in the meat matrix is equally bioavailable.

Animals↗

PubMed2004

Intestinal tissue engineering: from regenerative medicine to model systems.

BACKGROUND: Tissue engineering is a rapidly emerging field that combines the established disciplines of engineering, biology, and medicine with the goal of fabricating viable tissues and organs. Although initially targeted for applications in regenerative medicine, a novel application of this technology has been to generate experimental model systems for studying biological mechanisms and testing the efficacy of potential therapies. METHODS: Review and analysis of the literature. RESULTS AND CONCLUSION: We present the limitations of existing models and provide examples of how tissue engineering has allowed for the generation of new models that may overcome these limitations.

Animals↗

PubMed1993

The SCID mouse: relevance as an animal model system for studying human disease.

The simultaneous description some 5 years ago of two methods for the partial reconstitution of a human immune system in severe combined immune-deficient (SCID) mice (collectively, human:SCID mice) was met with great enthusiasm. At the time, it was hoped that human:SCID mice would provide experimental animal model systems for studying human disease and the human immune system. Many of these hopes have been borne out. Importantly, the experimental results obtained from these chimeric human/animal studies appear to be relevant to human disease and immune function. In spite of these glowing achievements, the SCID mouse may not represent the optimal experimental system with which to address these questions. The incomplete penetrance ("leakiness") of the scid mutation and the recent discovery that the mutation is not lymphoid specific, but rather affects a general DNA repair pathway, will only serve to complicate the interpretation of already complex biological interactions. Recently other immune-deficient mice have been described that appear to overcome one or both of these problems and thus these mice could represent improved hosts for the adaptive transfer of a human immune system. The current status of the SCID mouse in light of these new findings is discussed.

Animals↗

PubMed1975

A model system for investigating the biliary excretion of an anion in the rat.

1. The biliary excretion of phenolphthalein di[35S]sulphate was studied in rats. 2. The conjugate was administered by continuous infusion at rates of 3, 4.5, 6, 9 and 12 mug/min, and kinetic analysis of the rate of biliary excretion was consistent with a two-compartment open-model system. 3. The results obtained after single injections of the ester were also consistent with the model. 4. An essential feature of the model is the presence of a compartment into which the ester may pass as an alternative to direct excretion via the bile. 5. It is suggested that such a compartment may be located within the liver.

Animals↗