Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.
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PMID:Arenavirus chemotherapy--retrospect and prospect. 108 27

The nuclear magnetic spin-lattice relaxation rates of water protons are reported for solutions of manganese(II), copper(II), and chromium(III) cage complexes of the sarcophagine type. As simple aqueous solutions, the complexes are only modest magnetic relaxation agents, presumably because they lack protons on atoms in the first-coordination-sphere protons that are sufficiently labile to mix the large relaxation rate at the metal complex with that of the bulk solvent. The relaxation is approximately modeled using spectral density functions derived for translational diffusion of the interacting dipole moments with the modification that the electron spin relaxation rate is directly included as a contribution to the correlation time. In all cases studied, the electron spin relaxation rate is sufficiently large that it contributes directly to the water-proton spin relaxation process. The poor relaxation efficiency of the cage compound may, however, be improved dramatically by binding the complex to a protein. The efficiency is improved even further if the rotational motion of the protein is reduced drastically by an intermolecular cross-linking reaction. The relaxation efficiency of the cross-linked protein-cage complexes rivals that of the best first-coordination-sphere relaxation agents like [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]-.
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PMID:Nuclear magnetic spin-lattice relaxation of water protons caused by metal cage compounds. 131 46

Tetrathiomolybdate (TTM) has been examined for its effect on copper metabolism in mouse hepatocytes in primary culture and human fibroblasts. It decreased the amount of copper inside hepatocytes, decreased the rate of copper uptake by hepatocytes in a concentration dependent manner, and increased the copper efflux from the cells. TTM appeared to remove copper preferentially from the labile pool, but with a lower affinity than cage chelators. In fibroblasts, TTM only had a marginal effect on copper levels below a concentration of 100 microM and had no clear effect on the rate of copper uptake. TTM was not toxic to human fibroblasts, but in some preparations, a concentration of more than 50 microM was toxic to hepatocytes.
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PMID:The effect of tetrathiomolybdate on the metabolism of copper by hepatocytes and fibroblasts. 248 38

Disorders of copper storage are usually treated by chelation therapy. It is generally thought that the chelators act by mobilizing copper from the liver, hence allowing excretion in the urine. This paper has examined the effect of chelators on copper uptake and storage in mouse hepatocytes. Penicillamine, a clinically important chelator, does not block the uptake of copper or remove copper from hepatocytes. Two other copper chelators, sar and diamsar, which form very stable and kinetically inert Cu2+ complexes by encapsulating the metal ion in an organic cage, were shown to block copper accumulation by the cells and to remove up to 80% of cell-associated copper. They also removed most (approximately 80%) of the 64Cu accumulated by the cells in 30 min, but released only a small percentage (less than 20%) of that accumulated over 18 h. The results show that copper in the hepatocyte can be divided into at least two pools, an easily accessible one, and another, not removable even after long-term incubation with any of the chelators. Most of the copper normally found in the cell appeared to be associated with the former pool.
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PMID:Effect of chelators on copper metabolism and copper pools in mouse hepatocytes. 270 27

One hundred forty pubertal Swiss-Webster female mice (Mus musculus) were assigned randomly to a purified diet modified to contain 1, 2, 3, 4, 5 and 6 ppm copper as copper carbonate (Diets 1 thru 6, respectively). Diet 7 was a commercial rodent laboratory diet containing 11 ppm copper. Following 60 days of prefeeding, the breeding regimen was initiated by introducing a proven breeder male into each cage of 10 females in the afternoon and removing them the next morning. The breeding regimen was conducted for 28 days and females were either sacrificed at 24 or 96 hours following detection of a vaginal plug. Body weight, hematocrit, heart weight, hemoglobin concentration, ova recovery rate and fertilization rate were recorded for each female. All morphologically normal embryos collected 24 hours after detection of the vaginal plug were cultured and development in vitro evaluated. Body weight, hemoglobin concentration and hematocrit were lower (P less than .05), and heart weight and percent body weight occupied by the heart (%BWOH) were higher (P less than .05) in mice fed Diet 1. Heart weight and %BWOH were not different among mice fed Diets 2 thru 6 (P greater than .05). Ova recovery rate and fertilization rate were significantly reduced in mice maintained on Diet 1. The incidence of in vitro blastocyst formation was lower in embryos collected from females fed Diets 1 and 3 (P less than .05). Blastocyst hatching in vitro was not observed in embryos from females maintained on Diet 1, and was greater in embryos from females fed Diets 4, 5, and 7 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of dietary copper on reproduction, growth and the cardiovascular system in Swiss-Webster female mice. 293 89

Two systems for exposing mice to 2,450-MHz electromagnetic fields are described. In a waveguide system, four mice were placed in a Styrofoam cage and exposed dorsally to circularly polarized electromagnetic fields. The temperature and humidity in the mouse holder were kept constant by forced-air ventilation. For 1-W input power to the waveguide, the average specific absorption rate (SAR) was determined by twin-well calorimetry to be 3.60 +/- 0.11 (SE) W/kg in 27-g mice. The maximum SAR at the skin surface determined thermographically was 8.36 W/kg in the head of the mouse. The second system was a miniature anechoic chamber. Six mice were irradiated dorsally to far field plane waves. Copper shielding and high-temperature absorbing material were lined inside the chamber to accommodate the high input power. The air ventilation at the location of the mice was separately controlled so that any heating in the absorber would not affect the animals. For 1-W input power, the average SAR was 0.17 +/- 0.01 W/kg and the maximum SAR at the skin surface was 0.41 W/kg in the animal when irradiated with body axis parallel to the E field; the SARs were 0.11 +/- 0.01 W/kg and 0.64 W/kg, respectively, when irradiated perpendicular to the E field.
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PMID:Systems for exposing mice to 2,450-MHz electromagnetic fields. 718 63

The diaphragmatic electromyogram has been measured as an index of the level of diaphragmatic activation. The diaphragmatic electromyogram, however, even when measured by intramuscular electrodes, can be artifactually altered by a change in lung volume (A. Brancatisano, S. M. Kelly, A. Tully, S. H. Loring, and L. A. Engel. J. Appl. Physiol. 66: 1699-1705, 1989) or by a change in body position. The parasternal intercostal muscle may be less subject to the mechanisms that are believed to produce this artifactual change. We asked whether the parasternal intercostal electromyographic activity could be reliable when lung volume changes. Six supine rabbits were anesthetized with ketamine and xylazine. Fine bipolar copper wires, with their tips exposed, were inserted into the left parasternal intercostal muscle in the third interspace. A stimulus that was three times maximal was applied to the corresponding intercostal nerve, and the resulting action potential (AP) was photographed. Parasternal intercostal muscle length was measured by sonomicrometry over the vital capacity range. There were small nonsignificant changes in the AP from functional residual capacity (FRC) to total lung capacity. From FRC to residual volume there was variation in the AP. The AP was also quite stable when regional conductivity was altered but showed variation when the parasternal intercostal muscle length change was accentuated by traction on the rib cage. We conclude that the parasternal intercostal electromyographic activity can be reliably used to measure inspiratory motoneuron output to it over the range of lung volumes from FRC to total lung capacity.
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PMID:Stability of evoked parasternal intercostal muscle electromyogram at increased end-expiratory lung volume. 761 59

An experimental study on photodynamic effect of newly developed photosensitizer CPD4 with pulsed copper-vapor laser and pumped dye laser to mouse transplanted tumor (CT26) was carried out. The results showed that: (1) Ten days after treatment by CPD4 with 630nm laser, the mean tumor volume of control group (n = 9) was 1.0 +/- 0.68cm3, while that of treatment group (n = 18) was 0.45 +/- 0.5cm3 (P < 0.01), with an inhibitory rate of 55%. In the treatment group, 8 mice that were treated with a dose > or = 50mg/kg(iv) of CPD4, 280mW/cm2 of laser power density and 10 minutes of irradiation, were all cured with survival time over 6 months, while that of mice in the control group was 28.2 days (2) Under certain condition (light energy 120 J/cm2), with CPD4 as a sensitizer, the mean depths of tumor necrosis were 4.9 +/- 1.0mm (n = 5), 2.8 +/- 1.1mm(n = 11), 1.8 +/- 0.5mm(n = 9) for wavelength of 670nm, 630nm and 510nm, respectively (P < 0.01). When a conventional photosensitizer hematoporphyrin derivative was used, the depths of tumor necrosis were 0 (n = 6) 2.3 +/- 0.3 (n = 5) and 2.8 +/- 1.2 (n = 5)mm for 670, 630 and 510nm, respectively. Based on the above mentioned results, a rational treatment condition in clinical application of CPD4 with copper-vapor laser and pumped dye laser was suggested.
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PMID:[Photodynamic effect of chlorophyll derivative (CPD4) with pulsed copper-vapor laser on mouse transplanted tumor]. 792 58

Large cavities and portals are present in the nanoscale molecular architectures formed from dithiocarbamate-functionalized resorcarene ligands and zinc(II) or copper(III) ions. With Zn(II) a molecular loop based on a triangle of resorcarene cups is prepared-the cavity is circular (shown on the left). A molecular cage based on a distorted tetrahedron of four resorcarene ligands assembled by eight Cu(III) ions contains triangular-shaped portals suitable for guest passage (shown on the right).
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PMID:Resorcarene-Based Nanoarchitectures: Metal-Directed Assembly of a Molecular Loop and Tetrahedron. 1064 53

Oxidative modification of low-density lipoprotein (LDL) plays a pivotal role in the pathogenesis of atherosclerosis. Increasing the resistance of LDL to oxidation may therefore mitigate, or even prevent, atherosclerosis. A new water-soluble C60 derivative, hexasulfobutyl[60]fullerene [C60 - (CH2CH2CH2CH2-SO3Na)6; FC4S], consisting of 6 sulfobutyl moieties covalently bound onto the C60 cage is a potent free radical scavenger. This study explored the antioxidative effect of sulfobutylated fullerene derivatives (FC4S) on LDL oxidation. FC4S was found to be effective in protecting LDL against oxidation induced by either Cu2+ or azo peroxyl radicals generated initially in the aqueous or lipophilic phase, respectively. Levels of the oxidative products, conjugated diene and thiobarbituric acid-reactive substances, and the relative electrophoresis mobility of the LDL were decreased. The addition of 20 microM FC4S at the early stage of oxidation increased the kinetic lag time from 69 +/- 11 to 14 +/- 10 min (P < 0.05) and decreased the propagation rate from 17.1 +/- 2.6 to 6.3 +/- 1.0 mOD/min (P < 0. 005). Persistent suppression of peroxidation reaction was observed upon further addition of FC4S after full consumption of all endogenous antioxidants during the propagation period. Intravenous injection of hypercholesterolemic rabbits with FC4S (1 mg/kg/day) efficiently decreased atheroma formation. Data substantiate the use of FC4S as an excellent hydrophilic antioxidant in protecting atheroma formation, via removing free radicals, in either aqueous or lipophilic phase.
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PMID:Water-soluble Hexasulfobutyl[60]fullerene inhibit low-density lipoprotein oxidation in aqueous and lipophilic phases. 1080 13


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