Crystal structure of bovine Cu,Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands.
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An electron density map at 3 angstrom resolution has been calculated for Cu2+, Zn2+ superoxide dismutase from bovine erythrocytes, and the course of the main chain has been traced. The dominant structural feature is an 8-stranded barrel of antiparallel beta-pleated sheet. There is one very short helical section and two long loops of non-repetitive structure. The Cu and Zn are bound between the loops and one side of the beta barrel and are about 6 Angstrom apart, with a common histidine ligand. The Cu has four histidine ligands in a somewhat distorted square plane, and the Zn has three histidines and an aspartate in approximately tetrahedral arrangement. The two coppers of a dimer are about 34 Angstrom apart. The two subunits have essentially the same conformation and have an extensive contact area that mainly involves hydrophobic side chain interactions. The overall folding pattern of the polypeptide chain is very similar to that of an immunoglobulin domain. (+info)
Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma.
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Orthotopic liver transplantation (OLT) alone for unresectable cholangiocarcinoma is often associated with early disease relapse and limited survival. Because of these discouraging results, most programs have abandoned OLT for cholangiocarcinoma. However, a small percentage of patients have achieved prolonged survival after OLT, suggesting that adjuvant approaches could perhaps improve the survival outcome. Based on these concepts, a protocol was developed at the Mayo Clinic using preoperative irradiation and chemotherapy for patients with cholangiocarcinoma. We report our initial results with this pilot experience. Patients with unresectable cholangiocarcinoma above the cystic duct without intrahepatic or extrahepatic metastases were eligible. Patients initially received external-beam irradiation plus bolus fluorouracil (5-FU), followed by brachytherapy with iridium and concomitant protracted venous infusion of 5-FU. 5-FU was then administered continuously through an ambulatory infusion pump until OLT. After irradiation, patients underwent an exploratory laparotomy to exclude metastatic disease. To date, 19 patients have been enrolled onto the study and have been treated with irradiation. Eight patients did not go on to OLT because of the presence of metastasis at the time of exploratory laparotomy (n = 6), subsequent development of malignant ascites (n = 1), or death from intrahepatic biliary sepsis (n = 1). Eleven patients completed the protocol with successful OLT. Except for 1 patient, all had early-stage disease (stages I and II) in the explanted liver. All patients who underwent OLT are alive, 3 patients are at risk at 12 months or less, and the remaining 8 patients have a median follow-up of 44 months (range, 17 to 83 months; 7 of 9 patients > 36 months). Only 1 patient developed tumor relapse. OLT in combination with preoperative irradiation and chemotherapy is associated with prolonged disease-free and overall survival in highly selected patients with early-stage cholangiocarcinoma. (+info)
Effects of cis-Dichlorudiammineplatinum (II) and related transition metal complexes on Escherichia Coli.
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A number of transition metal complexes, including the cis and trans isomers of dichlorodiammineplatinum (II), six complexes of rhodium (I), two of iridium (I), and one of ruthenium (II) have been tested for their ability to induce lambda prophage, to produce filamentous growth of Escherichia coli, and to be selectively toxic for strains with defects in the deoxyribonucleic acid repair system. Dichlorotetrakis(dimethylsulfoxide)ruthenium II [RuCl(2) (DMSO)(4)] was strictly similar to cis-dichlorodiammineplatinum II [cis PtCl(2) (NH(3))(2)] in the test for lambda induction, filamentous growth production, and selective toxicity for a recA(-) strain. [Rh COD 1,10-phenanthroline](+) Cl(-), though more toxic for recA(-) than for rec(+)E. coli, was scarcely effective in the test for filamentous growth and did not induce prophage. None of the other tested compounds showed any similarity with cis-PtCl(2)(NH(3))(2). Due to the interesting results obtained with cis-PtCl(2)(NH(3))(2) as an antitumor agent, it seems reasonable to propose RuCl(2)(DMSO)(4) as a potential antitumor substance. (+info)
Comparing cardiac action potentials recorded with metal and glass microelectrodes.
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Machine-pulled high-impedance glass capillary microelectrode is standard for transmembrane potential (TMP) recordings. However, it is fragile and difficult to impale, especially in beating myocardial tissues. We hypothesize that a high-impedance pure iridium metal electrode can be used as an alternative to the glass microelectrode for TMP recording. The TMPs were simultaneously recorded from isolated perfused swine right ventricles with a metal microelectrode and a standard glass microelectrode during pacing and during ventricular fibrillation. The basic morphology of TMP recorded with these electrodes was comparable. The action potential duration (APD) at 90% repolarization was 241 +/- 29 ms for the metal microelectrode and 236 +/- 31 ms for the glass microelectrode with a good correlation (r = 0.99, P < 0.0001). The maximum slope value of the APD restitution curves during pacing was also significantly correlated. One metal microelectrode and >20 glass microelectrodes were needed per study. We conclude that, in isolated perfused swine right ventricles, the TMP recorded by the metal microelectrode is comparable with that recorded by the glass microelectrode. Because the metal microelectrode is more durable than the glass microelectrode, it can serve as an alternative for APD recording and for restitution analyses. (+info)
Effect of intracoronary gamma-radiation therapy on in-stent restenosis: An intravascular ultrasound analysis from the gamma-1 study.
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BACKGROUND: The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis. METHODS AND RESULTS: After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients. CONCLUSIONS: gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients. (+info)
Accretion rates of meteorites and cosmic dust in the Early Ordovician.
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Abundant fossil meteorites in marine, condensed Lower Ordovician limestones from Kinnekulle, Sweden, indicate that accretion rates of meteorites were one to two orders of magnitude higher during an interval of the Early Ordovician than at present. Osmium isotope and iridium analyses of whole-rock limestone indicate a coeval enhancement of one order of magnitude in the influx rate of cosmic dust. Enhanced accretion of cosmic matter may be related to the disruption of the L chondrite parent body around 500 million years ago. (+info)
Feasibility studies in rats fed heavy metals as multiple nutrient markers.
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The nitrates of five metals (cerium, terbium, ytterbium, lutetium, and iridium) were fed to rats to determine the feasibility of their use as nonabsorbed, multiple markers for recovery, passage, and indirect apparant digestibility studies. Fecal recovery of a single oral dose was completed within 72 hours. When the salts were mixed into the diet, 48-96 hours was required to establish a steady-state concentration of markers in feces. The diurnal variation of cerium in feces was found to be considerable when it was fed twice daily as a single dose prior to each feeding. When incorporated into the diet, negligible diurnal variation in fecal concentration was noted with lutetium, and small variation was seen with other metals. In nutrient apparent digestibility studies, good agreement was generally found between direct and indirect multiple marker methods. Experiments with a daily intake marker suggest that cerium was not satisfactory as a multiple marker in which neutron activation analysis was the method of determination. (+info)
Remarkably selective iridium catalysts for the elaboration of aromatic C-H bonds.
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Arylboron compounds have intriguing properties and are important building blocks for chemical synthesis. A family of Ir catalysts now enables the direct synthesis of arylboron compounds from aromatic hydrocarbons and boranes under "solventless" conditions. The Ir catalysts are highly selective for C-H activation and do not interfere with subsequent in situ transformations, including Pd-mediated cross-couplings with aryl halides. By virtue of their favorable activities and exceptional selectivities, these Ir catalysts impart the synthetic versatility of arylboron reagents to C-H bonds in aromatic and heteroaromatic hydrocarbons. (+info)