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At least 703 records · Page 39Linked to original sources
PubMed1983

Physicochemical properties and stability of anthralin in model systems and human skin.

The physico-chemical properties and the stability of anthralin, a potent antipsoriatic agent, has been investigated in model systems by optical absorption and fluorescence spectroscopy and by gas chromatography coupled to mass spectrometry. Systematic studies were carried out on anthralin and its oxidation products (1,8-dihydroxyanthraquinone and 1,8-1',8'-tetrahydroxydianthron). Anthralin and 1,8-dihydroxyanthraquinone are shown to readily bind to human serum albumin and not to DNA. Anthralin bound to albumin readily oxidizes, yielding the 1,8-dihydroxyanthraquinone which is fairly stable. These results are correlated with those obtained with intact whole human epidermis and suction blister fluid showing that, in the former case, anthralin binds to protein as suggested by absorption and fluorescence spectroscopies. Gas chromatography-mass spectrometry analysis makes it easy to detect anthralin and 1,8-dihydroxyanthraquinone in suction blister fluid doped with anthralin but not in suction blister obtained after topical application on normal human skin.

Anthracenes↗
PubMed1983

The effects of fixation by combination of glutaraldehyde/dimethyl suberimidate. Use of collagen as a model system.

The fixative behavior of glutaraldehyde/dimethyl suberimidate in combination was studied using reconstituted fibrils of type I calf skin collagen as a model system and comparing electron-optical data and chemical data by a computer-aided correlation procedure. The results confirm that the structural preservation of collagen obtained using prefixation in glutaraldehyde followed by dimethyl suberimidate fixation is less than when using dimethyl suberimidate and postfixation in glutaraldehyde. Furthermore, glutaraldehyde preserves the structure of collagen to a lesser degree than dimethyl suberimidate. With the combination of the two fixatives, the preservation of fine structure of collagen obtained is less than that when using dimethyl suberimidate alone.

Aldehydes↗
PubMed1984

Synthesis and degradation of interconvertible enzymes. Kinetic equations of a model system.

Steady-state and kinetic equations have been developed which characterize the rates of formation, interconversion, and degradation of an enzyme protein subject to reversible phosphorylation. The theoretical model system incorporates separate fractional degradative rate constants for the phosphorylated and dephosphorylated protein species. The classical models for interconvertible enzymes, and for protein turnover, are special limiting situations of the general model presented here.

Enzymes↗
PubMed2005

A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis.

Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-alpha and interleukin-1alpha, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set.

Apoptosis↗
PubMed1985

Determination of metabolites of cytochrome P-450 model systems using high-performance liquid chromatography.

High-performance liquid chromatographic techniques were developed for the simultaneous detection of metabolites in a cytochrome P-450 model system composed of NADH, haemoglobin and methylene blue. Monohydroxylated metabolites were determined following aniline, acetanilide and phenol hydroxylations. 4-Aminoantipyrine, 7-hydroxycoumarin and p-nitrophenol were determined after dealkylation of 4-N,N-dimethylamino-antipyrine, 7-ethoxycoumarin and p-nitroanisole. These substrates are commonly used for measuring cytochrome P-450 activities. Treatment of the samples was minimal, consisting of a simple deproteinization, and did not involve any organic extraction. Separations were carried out on reversed-phase columns and the products were detected by UV adsorption. Separations were completed in less than 15 min and the detection limits were between 0.5 and 4 microM.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1991

Molecular dynamics of water in foods and related model systems: multinuclear spin relaxation studies and comparison with theoretical calculations.

A review of recent studies of molecular dynamics of water in foods and model systems is presented, and the theoretical results are compared with experimental data obtained by several techniques. Both theoretical and experimental approaches are discussed for electrolytes, carbohydrates, and food proteins in solution. Theoretical results from Monte Carlo simulations are compared with experimental NMR relaxation data for quadrupolar nuclei such as those of deuterium and oxygen-17. Hydration studies of wheat, soybean, corn, and myofibrillar proteins by multinuclear spin relaxation techniques are discussed, and several new approaches to the analysis of the experimental data are considered. Correlation times of water motions in hydrated food systems are determined from NMR and dielectric relaxation data. The values of the correlation times for dilute solutions of electrolytes and carbohydrates estimated by NMR are in good agreement with those calculated from dielectric relaxation data, but seem to differ significantly from those proposed from Monte Carlo simulations. Several new and important results concerning the hydration of potato and cereal starches are presented, showing the very different hydration behaviors of these two major groups of starches. The combination of molecular dynamics computations with NMR relaxation techniques will hopefully stimulate novel technological developments in food engineering based on such fundamental studies.

Carbohydrates↗
PubMed1989

Comparative mechanisms of vitamin B6-catalyzed beta-decarboxylation and beta-dephosphonylation in model systems.

Reaction pathways and mechanisms of vitamin B6-catalyzed beta-decarboxylation and beta-dephosphonylation of aminocarboxylic and aminophosphonic acids in model systems are compared. It was found that both reactions require prior transamination of an aldimine intermediate to a ketimine. For ketimines having carboxylate or phosphonate groups substituted on the beta-carbon atoms of the keto acid residue, there is a hydrogen ion or metal ion-activated covalent bond pathway which involves a shift of electron pairs toward the coordinated ketimine nitrogen, leading to beta-gamma, C-C or C-P bond fission and release of carbon dioxide or metaphosphate, respectively. Comparison of these reactions indicates that beta-decarboxylation is 10(6) faster than the corresponding dephosphonylation reaction. Since only a few studies of vitamin B6-catalyzed dephosphonylation have been carried out, suggestions are made for further studies with substrates designed to elucidate the reaction mechanisms involved.

Amino Acids↗
PubMed2001

Biological characteristics of carcinomatosa pleuritis in orthotopic model systems using immune-deficient rats.

We assessed the association of vascular endothelial growth factor (VEGF) on the formation of carcinomatosa pleuritis in orthotopic model systems. Immune-deficient rats were inoculated with PC-14 cells into i) a subpleural space of the parietal pleura after pneumonectomy or ii) into the thoracic cavity directly. The rats bearing tumor cells were randomly separated into two groups: non-treatment and treatment with anti-VEGF neutralizing antibody groups. At the time of the autopsy, all rats developed gross pleural dissemination with/without malignant effusions. In the first model, despite no significant difference in the mean volume of the subpleural tumors between the groups, the degree of dissemination was suppressed in the treatment group with less tumor vasculature and with reduced expression of autocrine motility factor receptor (AMFR) in tumor cells. In the second model, although the inhibitory effect on dissemination was not clear, the formation of pleural effusion was inhibited in the treatment group. In addition to the ability of vascular permeability, the results demonstrated here showed the possible association of VEGF with the development of pleural dissemination/metastasis in the context of blood/lymphatic routes and cancer cell motility affected by AMFR.

Adenocarcinoma↗
PubMed1993

The phylogenetic position of the zebrafish (Danio rerio), a model system in developmental biology: an invitation to the comparative method.

The zebrafish, Danio (Brachydanio) rerio, has become one of the most widely studied model systems in developmental biology. We present a DNA-based phylogeny of zebrafish and other species of the genus Danio, and the genera Rasbora, Puntius and Cyprinus. Homologous regions of the large (16S) mitochondrial ribosomal RNA gene were amplified by the polymerase chain reaction and directly sequenced. The phylogeny revealed: (i) the zebrafish, Danio (Brachydanio) rerio, is identical in its 16S sequence to its aquarium breeding morph, the leopard danio; (ii) the pearl danio (Danio albolineatus) is more closely related to the zebrafish than the giant danio (Danio aequipinnatus); and (iii) species of the genus Rasbora (hetermorpha, trilineata, elegans, pauciperforata, dorsiocellata) are more closely related to the danios than members of the genus Puntius (tetrazona, conchonius) and Cyprinus, the carp. All of these species are readily available in the aquarium trade, easily kept and bred in captivity, and amenable to developmental work. It is hoped that this molecular phylogeny will invite developmental biologists to use the comparative method to ask questions about function (e.g. cellular and genetic aspects) and evolution of zebrafish developmental biology in a phylogenetic context.

Animals↗
PubMedDate not supplied

Drosophila spermatogenesis as a model system.

Spermatogenesis is very similar throughout the animal kingdom and is probably based on very old evolutionarily principles. Drosophila can serve as a suitable model system to understand the underlying processes. The molecular and ultrastructural data obtained for Drosophila germ cell development can be applied to understanding spermatogenesis in other organisms, including humans. Various methods used in studies of Drosophila spermatogenesis are presented together with observations which exemplify this conclusion.

Animals↗
PubMedDate not supplied

Dictyostelium discoideum: a promising centrosome model system.

The centrosome of the slime mould Dictyostelium discoideum displays a morphology markedly different from centriolar centrosomes or yeast spindle pole bodies, while fulfilling the same conserved functions in the organization of the microtubule cytoskeleton. Recent advances suggest that the Dictyostelium centrosome may offer an interesting model system, usefully complementing other well-studied centrosome models. The establishment of an isolation procedure and the generation of a range of monoclonal antibodies have been achieved, which are important pre-requisites for biochemical investigation. Furthermore, the role of the centrosome in cell motility and centrosome duplication process have been investigated using cells with GFP-labelled centrosomes.

Animals↗
PubMed1984

Model system to study interaction of platelets with damaged arterial wall. I. Inhibition of platelet adhesion to subendothelium by aspirin and dipyridamole.

An experimental model system has been developed to study the interaction of platelets with a damaged vessel wall, in vivo, without deep surgical intervention. Endothelium of the central ear artery of an anesthetized rabbit is damaged by placing artery forceps on the ear directly over the vessel. Forceps are removed 30 min later and blood flow resumes. After 30 min, blood is washed out with Tyrode's solution and the vessel is perfused with 1% glutaraldehyde solution. Tissue containing the vessel is then removed and further prepared for scanning and transmission electron microscopy. Damage to the endothelium observed by scanning electron microscopy included separation of adjacent endothelial cells (EC); partial destruction and lifting up of some EC, exposing subendothelium; and denudation of larger areas of endothelium. Disc-shaped platelets were seen clinging to some damaged endothelial cells. Platelets adhered, formed pseudopods, and spread over the surface of some areas of exposed subendothelium. The extent of platelet adhesion to exposed subendothelium was estimated by eight "blind" evaluators and the average taken. Aspirin (8 mg/kg, ip) significantly inhibited adhesion (P less than 0.05) when compared to controls. No other agent tested gave significant inhibition after a single treatment. Dipyridamole (1.5 mg/kg, ip) given five times on 3 successive days, inhibited adhesion significantly (P less than 0.001). Heparin (800 U/kg, iv) or dipyridamole (0.7 mg/kg, ip) enhanced the inhibitory effect of aspirin (8 mg/kg, ip), with either combined treatment giving P less than 0.001.

Animals↗
PubMed2003

A novel model system for studying the double-edged roles of nitric oxide production in pancreatic cancer growth and metastasis.

In the present study, a model system for studying the role of nitric oxide (NO) in tumor growth and metastasis was reported. Incubation of Panc02 murine pancreatic adenocarcinoma cells in vitro with cytokines and interferon led to heterogeneous expression of NO synthase II (NOS II) protein. Clonal sublines expressing different levels of NOS II were then established using a limited dilution technique. After orthotopical implantation into the pancreas of syngeneic C57BL/6 mice, clones with a low level of NOS II expression produced tumors in pancreas, metastasized to the liver, and formed ascites, whereas those having a high level of NOS II expression did not. Liver-metastasis variants having low to high metastatic ability were also established using in vivo/in vitro passage. Compared with parental Panc02 cells exhibiting a high level of NOS II expression, these variants had a decreased level of NOS II expression. Furthermore, the heterogeneous Panc02 cells were injected intravenously into a large number of syngeneic mice. Variants that metastasized to the liver, lung, skin, peritoneum, ovary, and lymph nodes were established. All of the metastatic variants exhibited a lower level of NOS II expression than the parental Panc02 cell line did. However, the phenotypes of NOS II induction and metastatic ability were unstable. Multiple in vitro/in vivo selection led to stable low NOS II expression and high metastatic potential. Finally, to further confirm the role of NOS II expression derived from tumor cells in metastasis, poorly metastatic Panc02-H0 and highly metastatic Panc02-H7 cells were injected into the pancreas of syngeneic NOS II(-/-) mice, and groups of mice received i.p. injections of either phosphate-buffered saline or L-N(6)-(1-iminoethyl) lysine. Inhibition of NOS II activity in vivo significantly promoted distant liver metastasis. Collectively, these data show that NOS II expression is highly heterogeneous and dynamically regulated, which can directly influence tumor growth and metastasis.

Adenocarcinoma↗
PubMed1990

Comprehensive assessment of AIDS patients using the behavioural systems model for nursing practice instrument.

The major changes resulting from the AIDS diagnosis and illness were measured, described and classified in the Behavioural Systems Model's eight subsystems--achievement, affiliative, aggressiveness/protectiveness, dependence, ingestive, eliminative, restorative and sexual. Thirty male AIDS patients with Kaposi's Sarcoma were drawn as a convenience sample from a major medical centre's outpatient clinic. The subjects self-rated their perceived changes in the above eight major areas, using a 140-item instrument (DBSM) consisting of 24 categories of changes distributed in the above eight areas. Patients reported changes in all categories and described them in terms of direction, quality and relative importance. Ordinal ranks of changes existed among the eight major subsystems' frequency and importance of change scores, as shown by ANOVA and Tukey's studentized t-tests of rank.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The generation and characterization of a radiation-resistant model system to study radioresistance in human breast cancer cells.

To systematically study the selection of radioresistant cells in clinically advanced breast cancer, a model system was generated by treating MDA-MB231 breast cancer cells with fractionated gamma radiation. A clonogenic assay of the surviving cell populations showed that 2-6 Gy per fraction resulted in a rapid selection of radioresistant populations, within three to five fractions. Irradiation with additional fractions after this initial increase did not increase the radioresistance of the surviving population significantly. Doses of 0.5 and 8 Gy per fraction were not effective in selecting radioresistant cells. To further determine the cause of the changes in radiosensitivity, 15 clones were isolated from the cell populations treated with 40 or 60 Gy with 2 or 4 Gy per fraction, respectively, and were analyzed for radiosensitivity. The average D(10) for these clones was 6.75 +/- 0.36 Gy, which was higher than that for the parental cell population (D(10) = 6.0 +/- 0.2 Gy). The operation of cell cycle checkpoints and the doubling time were similar for both the nonirradiated parental population and the isolated radioresistant subclones. In contrast, a decrease in the apoptotic potential was correlated (r = 0.7, P < 0.01) with increased survival after irradiation, suggesting that apoptosis is an important factor in determining radioresistance under our experimental conditions. We also isolated several subclones from the nonirradiated parental cell population and analyzed them to determine their radiosensitivity after fractionated irradiation. Ten fractions of 4 Gy (40 Gy in total) did not result in a significant increase in the radioresistance of these subclones compared to the irradiated cell populations. The possible mechanisms of the increased radioresistance after fractionated irradiation are discussed.

Apoptosis↗
PubMedDate not supplied

[A systemic model of the reproductive death of mammalian cells. The effect of radiation dose rate and fractionation].

On the basis of the previously developed systemic model a study was made of the effect of dose rate on the survival of mammalian cells, RBE of small doses of heavy ions, and fractionation of radiation. There was a good agreement between theoretical and experimental results. The calculations showed that D10 (10% survival dose) is a function of dose rate P even for such ions as helium and boron which, however, exhibited an insignificant dependence of D10 on P (within the range from (10(-1) to 1 cGy/min). The influence of repair and the rate of cell division on RBE of radiation was determined.

Animals↗
PubMed2001

Model system for evaluation of alternative splicing: exon skipping.

Alternative splicing of the primary RNA transcript is a common mechanism for generating protein diversity. A model system was developed to study this process in vitro that is useful for evaluation of splicing of transcripts expressed in cells that do not grow well in culture. The system was used to analyze skipping of exon 4 of the amelogenin message, normally expressed in ameloblast cells for a short interval during tooth enamel development. Amelogenins are highly conserved proteins resulting from extensive alternative splicing, with domains involved in a range of functions, including mineral formation and intercellular signaling. In the bovine gene, the very short intron 4 was predicted to inhibit inclusion of exon 4, because in murine ameloblasts, exon 4 is detectably included in mRNA, and intron 4 is longer than the bovine counterpart. Bovine intron 4 was lengthened, and this size increase enhanced exon 4 inclusion sixfold to eightfold, although splice site selection was inaccurate. Intron length, therefore, is not the sole determinant controlling amelogenin exon 4 inclusion, and cis-acting inhibitory elements may also be involved in exon skipping. This vector system allows evaluation of splicing of a tissue-specific RNA by focusing on exons of interest through transfection of heterologous cultured cells without complications attributable to background transcription of the gene being evaluated.

Alternative Splicing↗