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At least 865 records · Page 48Linked to original sources
PubMed2005

Reduced serotonin and 3-hydroxyanthranilic acid levels in serum of cystatin B-deficient mice, a model system for progressive myoclonus epilepsy.

PURPOSE: To evaluate the levels of tryptophan and its metabolites along serotonin (5-HT) and kynurenine (KYN) pathways in serum of progressive myoclonus epilepsy (EPM1) patients and cystatin B (CSTB)-deficient mice, a model system for EPM1. METHODS: Tryptophan and its metabolites along serotonin (5-HT) and KYN pathways were determined in serum of EPM1 patients and CSTB-deficient mice by reverse-phase high-pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS: Reduced levels of 5-HT and KYN intermediate metabolite 3-hydroxyanthranilic acid were found in serum of CSTB-deficient mice. A similar trend was found in EPM1 patients. Although tryptophan concentration was reduced in serum of EPM1 patients, no such decrease was observed in CSTB-deficient mice. CONCLUSIONS: The present study demonstrates that tryptophan metabolism along 5-HT and KYN pathways are disrupted in EPM1. Further studies are needed to elucidate the role of KYN pathway in pathogenesis of EPM1.

3-Hydroxyanthranilic Acid↗
PubMed1993

A new generation of model systems to study the blood brain barrier: the in vitro approach.

After an era of studying the unique permeability properties of cerebral endothelial cells with endogenous or exogenous tracers in vivo, the next generation of blood-brain barrier model systems was introduced, when the conditions for isolating the microvessels from brain tissue and culturing the endothelial cells were established. Recent advances in our knowledge of the blood-brain barrier have in part been made by studying the properties and function of cerebral endothelial cells with this in vitro approach. This review summarizes in brief the results obtained mainly from this rapidly growing field.

Animals↗
PubMed1994

Genetic analysis of an in vitro model system for human papillomavirus type 16-associated tumorigenesis.

We have investigated the genetic basis for malignant progression of an human papillomavirus type 16 immortalized human keratinocyte cell line (HPKIA) by somatic cell fusion. In this cell culture model system for human papillomavirus type 16-associated tumorigenesis, early passage cells (HPKIA-nt) are nontumorigenic, whereas gamma-irradiated late passage cells (HPKIA-t) are tumorigenic when tested in nude mice. Fusion of HPKIA-t cells with normal human keratinocytes or with HPKIA-nt gave rise to hybrid clones in which the tumorigenic phenotype is suppressed. This observation is in line with complementation studies conducted for other tumor cell systems and indicates that, also in the case of HPKIA-t cells, the tumorigenic phenotype is recessive. Hybrid clones derived by fusion of HPKIA-t with cells of the cervical carcinoma cell lines C4-I, HeLa, or C33A were also nontumorigenic. However, the tumorigenic phenotype was retained in all of the HPKIA-t x SiHa and HPKIA-t x MS751 hybrids tested. The cervical carcinoma cell lines SiHa and MS751, therefore, cannot complement the gene defect(s) related to tumor growth of HPKIA-t cells. This may suggest that HPKIA-t, SiHa, and MS751 cells share the same defect(s) in regulatory pathway(s) involved in tumor suppression. Differences in the steady state levels of viral E6-E7 transcripts were noted for most of the hybrid cells. The observations of this study underline the potential use of nontumorigenic and tumorigenic HPKIA cells to define genetic differences that may also correlate with tumor progression in vivo.

Animals↗
PubMed2001

Comparison of gas-phase free-radical populations in tobacco smoke and model systems by HPLC.

We used an improved method for trapping carbon-centered radicals (.R) from the gas-phase to compare radical suites trapped from various tobacco smoke and model smoke systems. Using a nitroxide trap, 3-amino-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (3AP), on solid support, we trapped radicals directly from the gas phase, washed them off the support, and analyzed them with HPLC. Separation of the trapped radicals showed that each tobacco type produced a unique radical suite of 4-10 distinct peaks. Gas mixtures used to model tobacco smoke consisted of nitric oxide, air, isoprene, and methanol. The model systems produced radical suites of four major and several minor peaks, two of which matched peaks in tobacco smoke chromatograms. Quantities of radicals trapped from tobacco smoke were: 54 +/- 2 nmol .R per Marlboro cigarette, 66 +/- 9 nmol .R per Djarum clove cigarette, and 185 +/- 9 nmol .R per Swisher Sweet cigar. In these experiments oxygen competes with the nitroxide trap for gas-phase radicals. A kinetic analysis of the O2 competition shows that actual radical concentrations in the smoke were approximately 100-fold higher than measured.

Butadienes↗
PubMed2006

Biological systems modeling and analysis: a biomolecular technique of the twenty-first century.

It is proposed that computational systems biology should be considered a biomolecular technique of the twenty-first century, because it complements experimental biology and bioinformatics in unique ways that will eventually lead to insights and a depth of understanding not achievable without systems approaches. This article begins with a summary of traditional and novel modeling techniques. In the second part, it proposes concept map modeling as a useful link between experimental biology and biological systems modeling and analysis. Concept map modeling requires the collaboration between biologist and modeler. The biologist designs a regulated connectivity diagram of processes comprising a biological system and also provides semi-quantitative information on stimuli and measured or expected responses of the system. The modeler converts this information through methods of forward and inverse modeling into a mathematical construct that can be used for simulations and to generate and test new hypotheses. The biologist and the modeler collaboratively interpret the results and devise improved concept maps. The third part of the article describes software, BST-Box, supporting the various modeling activities.

Computational Biology↗
PubMedDate not supplied

Cholesteryl ester efflux from extracellular and cellular elements of the arterial wall. Model systems in culture with cholesteryl linoleyl ether.

Cholesteryl ester (CE) accretion in human atheroma is a slow process during which lipoproteins infiltrate the arterial extracellular space and then gain entry into the cellular components. The present aim was to simulate this process in model systems in culture to learn whether cholesteryl ester transfer protein (CETP) may promote CE efflux at different stages of atheroma formation. To simulate CE efflux from arterial interstitium, cationized LDL labeled with 3H-cholesteryl linoleyl ether (3H-CLE) was added to fixed aortic smooth muscle cells (SMC) or to extracellular matrix. To study efflux of 3H-CLE taken up by cells via receptor-mediated endocytosis of LDL, the SMC cultures were fixed and permeabilized prior to the determination of CE efflux. The cellular model included macrophages, which had ingested acetylated LDL labeled with 3H-CLE. Efflux of 3H-CLE and 14C-CE was studied during postincubation of the labeled cultures with human lipoprotein deficient serum (LPDS) or partially purified CETP. As controls, we used SMC cultures incubated with albumin. In all systems, a 3- to 12-fold increase of 3H-CLE or 14C-CE efflux was found in the postincubation medium containing human LPDS or partially purified CETP when compared to controls. Permeabilization of the cells with saponin enhanced cellular 3H-CLE and 14C-CE efflux in the presence of human LPDS. The findings indicate that CETP may promote CE efflux from aortic interstitium or disintegrating cells. We propose that CETP may play an important role in aortic CE homeostasis under physiological and pathological conditions.

Animals↗
PubMed1999

Health promoting organizations: a systems model for advanced practice.

Nursing and other health care providers are challenged to create the future of health care. Health is synonymous with well-being framed holistically, mind, body, and spirit. Disparities are growing in health status for vulnerable population groups and the percentage of people who are uninsured is rising. New approaches to health care are needed in the current age of uncertainty. A comprehensive health promoting organization (HPO) model within an ecological systems framework is described. An operational example is delineated, Welcome Home Ministries HPO.

Health Maintenance Organizations↗
PubMed1995

[Establishment of an in vitro model system for the differentiation of synaptically coupled neurons from mouse embryonic stem cells]

The investigation of fundamental differentiation processes and toxic effects during the neurogenesis in the embryo is still difficult, since there are only a few suitable cellular model systems available so far. The isolation of neurons from early embryonic origin results in a very small amount of cells and a high number of laboratory animals is required for this purpose. Permanent tumor cell lines, able to differentiate into neuron-like cell types, are only a limited alternative for the use of primary cultures. None of the known permanent cell lines is capable to form terminally differentiated, synaptically coupled neurons in vitro. Embryonic stem (ES) cells can generate cell types of all 3 germ layers and provide a new possibility to study developmental processes on a cellular level. Nevertheless the successful differentiation of neurons from ES cells has not been shown. By using the ES cell line BLC 6 and cultivation of the cells in embryo-like aggregates (embryoid bodies), we were able to differentiate efficiently neuronal cells in vitro. The electrophysiological characterization of the BLC 6-derived neurons shows that these cells carry the complex electrical properties of postmitotic neurons and are coupled by inhibitory and excitatory synapses. The BLC 6 model probably represents the only developmental cell model suitable for studies from pluripotent stem cells to terminal differentiated neurons.

Journal Article↗
PubMed2000

Photochemical oxygen consumption sensitized by a porphyrin phosphorescent probe in two model systems.

Phosphorescence quenching of certain metalloporphyrins is used to measure tissue and microvascular pO(2). Oxygen quenching of metalloporphyrin triplet states creates singlet oxygen, which is highly reactive in biological systems, and these oxygen-consuming reactions are capable of perturbing tissue oxygenation. Kinetics of photochemical oxygen consumption were measured for a Pd-porphyrin in two model systems in vitro over a range of irradiances (1.34-134 mW cm(-2)). For a given irradiance, and, after correction for differing porphyrin concentrations, rates of oxygen consumption were similar when the Pd-porphyrin was bound to bovine serum albumin and when it was taken up by tumor cells in spheroids. At irradiances comparable to those used in imaging superficial anatomy, rates of oxygen consumption were sufficiently low (2.5 microM s(-1)) that tissue oxygenation would be reduced by a maximum of 6%. An irradiance of 20 mW cm(-2), however, initiated a rate of oxygen consumption capable of reducing tissue pO(2) by at least 20-40%. These measured rates of consumption impose limitations on the use of phosphorescence quenching in thick tissues. The irreversible photobleaching of the Pd-porphyrin was also measured indirectly. The bleaching branching ratio, 23 M(-1), is significantly lower than that of porphyrin photodynamic agents.

Animals↗
PubMed1997

Strategies for rapid deconvolution of combinational libraries: comparative evaluation using a model system.

Synthesis and testing of complex mixtures maximize the number of compounds that can be prepared and tested in a combinatorial library. When mixtures of compounds are screened, however, the identity of the compound(s) selected may depend on the deconvolution procedure employed. Previously, we developed a model system for evaluation of deconvolution procedures and used it to compare pooling strategies for iterative and noniterative deconvolution [Freier et al. J. Med. Chem. 1995, 38, 344-352]. We have now extended the model studies to include simulations of procedures with overlapping subsets such as subtractive pooling [Carell et al. Angew, Chem., Int. Ed. Engl. 1994, 33, 2061-2064], bogus coin pooling [Blake and Litzi-Davis. Bioconjugate Chem. 1992, 3, 510-513], and orthogonal pooling [D'Prez et al. J. Am. Chem. Soc. 1995, 117, 5405-5406]. These strategies required synthesis and testing of fewer subsets than did the more traditional nonoverlapping iterative strategies. The compounds identified using simulations of these strategies, however, were not the most active compounds in the library and were substantially less active than those identified by simulations of more traditional strategies.

Computer Simulation↗
PubMed2003

Myristyl dimethylamine oxide surfactant solutions: model systems for rheological research.

Aqueous surfactant solutions of entangled, rod-shaped micelles are often characterized by monoexponential stress-relaxation processes. This special phenomenon leads to relatively simple theoretical descriptions, and viscoelastic surfactant solutions can, therefore, also be used as simple model systems for studying fundamental principles of flow. Herein, we present a detailed study of the nonlinear rheological properties of aqueous myristyl dimethylamine oxide surfactant solutions. In the regime of small deformations, shear stresses, or shear rates, the dynamic features of the viscoelastic solutions are characterized by the simple equations of a Maxwell material. At elevated values of shear stresses or deformations, however, this simple model fails and nonlinear features, such as normal stresses, stress overshoots, or shear-thinning properties occur. All these phenomena can be described by a Maxwell-type differential constitutive equation, which was first proposed by Giesekus. It turns out that the experimental results are in fairly good agreement with the theoretical predictions, if the anisotropy factor alpha is equal to 0.5. Besides transient data and nonlinear steady-state measurements, many semiempirical laws, such as the Cox-Merz rule, the Yamamoto relation, the Laun equation, and the Gleissble mirror relationships are approximately satisfied. The dynamic properties discussed in this paper are of general importance and they are equally observed in different materials such as polymer, dye, or protein solutions.

Journal Article↗
PubMed2004

Distribution of exogenous delta-tocopherol between the membrane lipids and triacylglycerols of a cod muscle-triacylglycerol model system.

Membranes of muscle foods are more susceptible to oxidation than triacylglycerols. Hence, directing a lipid-soluble antioxidant into the membranes may reduce the oxidative deterioration of muscle tissue. The objective of this research was to use a model system of cod muscle and triacylglycerol to study the distribution of exogenous delta-tocopherol between the membranes and triacylglycerol fractions of muscle. When ethanol was the carrier solvent, more tocopherol was incorporated into the membranes than when oil was the carrier. Addition of tocopherol to the muscle before the triacylglycerol was added allowed more antioxidant to be incorporated into the membranes than for the case when the oil was added before the antioxidant. When the triacylglycerol was solid, the amount of tocopherol incorporated into the membranes was higher than if the triacylglycerol was liquid and the amount of tocopherol incorporated into the membranes was less dependent on the order of tocopherol and triacylglycerol addition. There was a competition between the membrane lipids and triacylglycerol for uptake of the delta-tocopherol. In some circumstances, some of the tocopherol did not enter either the membrane lipid or triacylglycerol phase.

Animals↗
PubMed1999

Medical complications during acute rehabilitation following spinal cord injury--current experience of the Model Systems.

OBJECTIVES: To examine the frequency of common secondary medical complications during acute rehabilitation in persons with new spinal cord injury (SCI). DESIGN: Survey and analysis of data in the National SCI Statistical Center (NSCISC) database. SETTING: Eighteen Model System SCI Centers located in urban, public medical centers around the United States. SUBJECTS: A total of 1,649 persons with new SCI entered into the NSCISC database between 1996 and mid-1998. RESULTS: Since 1992, the number of days from injury to admission to rehabilitation has steadily decreased, resulting in the increased potential to develop common secondary medical complications during rehabilitation hospitalization. Pressure ulcers occur with high frequency and were found to have developed in 23.7% of patients during rehabilitation. In addition, autonomic dysreflexia and atelectasis/pneumonia also occur with relative frequency during rehabilitation. Conversely, deep vein thrombosis and pulmonary embolism have decreased, most likely because of greater awareness of their potential to develop, as well as improved methods of prophylaxis. Cardiopulmonary arrest and gastrointestinal hemorrhage occur with relatively small frequency. The frequency of renal complications is difficult to gauge because of the decreasing number of patients who have any renal testing performed during rehabilitation hospitalization. CONCLUSION: The continued declining lengths of acute care hospitalization after SCI have resulted in the occurrence in the rehabilitation setting of medical complications that were previously seen in acute care. Greater awareness and attention to these conditions are necessary to reduce their occurrence, so that obstacles to recovery and functional improvement after SCI are minimized.

Autonomic Dysreflexia↗
PubMed2006

Model system for phenotypic characterization of sequence variations in the LDL receptor gene.

BACKGROUND: Sequence variations in the LDL receptor (LDLR) gene cause defects of LDLR protein production and function through different molecular mechanisms. Here we describe a cell model system for the phenotypic characterization of sequence variations in the LDLR gene. Well-known sequence variations belonging to LDLR classes 2 to 5 (p.G565V, p.I161D, p.Y828C, and p.V429M) were studied in CHO and HepG2 cells. METHODS: Expression of LDLR protein on the cell surface was detected by use of fluorescence-conjugated antibodies against the LDLR and the LDLR activity was measured by incubating the cells with fluorescently labeled and radiolabeled LDL. The intracellular locations of the LDLR mutants and wild-type were also investigated. RESULTS: The class 2A p.G565V sequence variant exhibited an intracellular distribution of LDLR with no active receptors on the cell surface. Both the class 3 p.I161D and class 4 p.Y828C sequence variants gave surface staining but had a reduced ability to bind or internalize LDL, respectively. By determining the intracellular locations of the receptors we were able to visualize the accumulation of the class 5 p.V429M sequence variant in endosomes by means of a specific marker, as well as confirming that the class 4 p.Y828C variant was not localized in clathrin-coated pits. Flow cytometry allowed us quantitatively to determine the amount and activity of receptors. To confirm the results of binding and cell association of fluorescently labeled LDL analyzed by flow cytometry, assays using 125I-labeled LDL were performed. In addition to a useful and valid alternative to radiolabeled LDL, the unique properties of fluorescently labeled LDL allowed a variety of detection technologies to be used. CONCLUSIONS: This new approach enables phenotypic characterization of sequence variations in the LDLR gene. The assays developed may be valuable for confirming the pathogenicity of novel missense sequence variations found throughout the LDLR gene.

Animals↗
PubMed1989

DNA replication of plasmids from gram-positive bacteria in Bacillus subtilis. Plasmid pUB110 as a model system.

The small high copy plasmids from gram-positive bacteria like pUB110 replicate via an asymmetric rolling circle mechanism. On the based of several criteria those plasmids could be subdivided in four different families. By analysing pUB110 replication in B. subtilis as a model system we have obtained information on the way by which initiation, elongation and termination in replication is accomplished in B. subtilis.

Bacillus subtilis↗
PubMed2001

Selective fortification of lysinoalanine, fructoselysine and N epsilon-carboxymethyllysine in casein model systems.

In the present study, a promising strategy to study nutritional effects of selected chemical reaction products formed in heat treated protein containing foods is addressed. In due course, a selective fortification of different marker compounds for lysine damage in casein-sugar mixtures was performed to provide model systems being applicable to investigate biological effects of the cross-link lysinoalanine (LAL), the MRPs fructoselysine (FL) and N epsilon-carboxymethyllysine (CML) in a casein-linked preparation. The three different model proteins, casein-LAL, casein-FL and casein-CML were prepared by heating casein either in strong alkaline conditions at 105 degrees C for 1 h, in the presence of glucose at 65 degrees C for 68 h, or in the presence of glyoxylic acid at 37 degrees C for 19 h. Finally, the degree of lysine modification achieved was 39%, 75% and 55% for the casein-LAL, casein-FL and casein-CML, respectively. The calculation of lysine recovery and the respective analysis of each single modified casein (LAL-, FL- and CML-MP) for the selected fortified compound and each other compound vice versa proved that the individual procedure provides a specific fortification for LAL, FL and CML, respectively. The modified proteins are suitable as reference model proteins to be investigated for specific biological and toxicological effects of casein-linked LAL, FL and CML.

Caseins↗
PubMed2004

Antioxidant activities of flavidin in different in vitro model systems.

Flavidin was isolated from Orchidaceae species and purified by silica gel column chromatography. The structure was identified using physical and spectral ((1)H, (13)C NMR, and mass) data. Antioxidant potency of flavidin was investigated employing various established in vitro model systems viz., beta-carotene-linoleate, 1,1-diphenyl-2-picryl hydrazyl (DPPH), phosphomolybdenum method, and scavenging of hydrogen peroxide methods. Flavidin showed very good antioxidant activity (90.2%) and almost equivalent to that of BHA at 50ppm level by beta-carotene-linoleate method. Radical scavenging activity of flavidin was compared with BHA at 5, 10, 20, and 40ppm concentration and flavidin showed more radical scavenging activity than BHA at all the tested concentrations. Furthermore, flavidin showed very good antioxidant capacity by the formation of phosphomolybdenum complex method. Besides this, flavidin showed effective hydrogen peroxide scavenging activity. The data obtained in the in vitro models clearly establish the antioxidant potency of flavidin. However, comprehensive studies need to be conducted to ascertain the in vivo safety of flavidin in experimental animal models. This is the first report on antioxidant activity of 9,10-dihydro-5H-phenanthro-(4,5 bcd)-pyrans/flavidin type of compounds.

Antioxidants↗
PubMed1986

In vitro human tumour model systems for investigating drug resistance.

Studies aimed at elucidating mechanisms responsible for the expression of drug resistance, which in the past have centred largely on the use of experimental animal model tumour systems, have more recently employed human tumour material. The advantages and limitations of the two main approaches adopted for in vitro studies, which have involved either direct use of biopsy specimens or work with human tumours established as continuous cell lines, are reviewed here. Reference is made to the need for strict characterization of the tumour cell populations under investigation, and their potential instability and heterogeneity, particularly in terms of drug responses, are discussed. Studies using human tumour cell lines have been more extensive than those employing biopsy material directly. Examples of investigations analysing drug resistance using lines derived from gliomas and from carcinomas of the lung, ovary or colon are reviewed. The question of whether these human tumour model systems accurately reflect the types of resistance encountered clinically is considered. Finally, several potential areas for further study are proposed centering on current investigations that address the issues of whether different mechanisms of resistance might be involved depending not only on the order of resistance expressed but also on the way in which such resistance was developed or induced.

Antineoplastic Combined Chemotherapy Protocols↗