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A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer.

OBJECTIVE: The detection rate of sentinel lymph nodes in patients with non-small cell lung cancer using isosulfan blue dye is too low for clinical use. Although exposure to radioactivity is reportedly minimal, special procedures are nonetheless required when a radioactive isotope is used as a tracer. Therefore, to eliminate the need for a radioactive tracer and to obtain a better detection rate than is obtained with isosulfan blue dye, we have developed a novel method that employs magnetite as the tracer. The aim of the present study was to test the feasibility of this technique. METHODS: The tracer employed was ferumoxides, a colloidal superparamagnetic iron oxide of nonstoichiometric magnetite. Thirty-eight non-small cell lung cancer patients participated in the study; each received 5 mL of ferumoxides, injected around the tumor intraoperatively. Fifteen minutes after injection, lung resection and lymph node dissection were carried out. The magnetic force within the lymph nodes was measured using a highly sensitive handheld magnetometer ex vivo. All lymph nodes were also subjected to conventional histological analysis. RESULTS: The rate of detection of sentinel lymph nodes was 81.6% (31/38). The accuracy, sensitivity, and false-negative rates were 96.8% (30/31), 85.7% (6/7), and 14.3% (1/7), respectively. CONCLUSION: Intraoperative sentinel lymph node mapping using ferumoxides and a highly sensitive magnetometer is a safe, accurate, and sensitive way to detect sentinel lymph nodes in non-small cell lung cancer patients.

Adult↗

Decay characteristics of the induced radioactivity in the target cave of a medical cyclotron.

After the transfer of the thick copper target plate irradiated with 30 MeV protons from a medical cyclotron, the gamma dose rate in the target cave was monitored every minute for 25 hours using wall-mounted gamma area monitors. The dose rate decay curve was fitted with four exponential functions. By analysing the slope of the exponentials the traces of radioactive 28Al, 56Mn 24Na and 59Fe were identified. The results were used to minimise personnel radiation exposure during maintenance work on the cyclotron.

Aluminum↗

Zinc ions inhibit the QP center of bovine heart mitochondrial bc1 complex by blocking a protonatable group.

Bovine heart bc1 complex is reversibly inhibited by zinc ions with an inhibition constant KI of 10(-7) M at pH > or = 7.0. Binding of zinc is at least a factor of 10 tighter than binding of any other metal ion tested. Essentially complete inhibition of ubihydroquinone:cytochrome c oxidoreductase activity is observed at concentrations of [Zn2+] > 5 microM. Zinc does not affect the Km for the substrates, ubihydroquinone or cytochrome c, but zinc inhibits reduction of the cytochromes by ubihydroquinone through the QP center. A radioactive binding assay using 65Zn revealed one high affinity binding site per bc1 complex with KD < or = 10(-7) M at pH = 7.0 and 3-4 additional low affinity binding sites (KD > 2 x 10(-6) M). Zinc binding does not depend on the redox state of the high potential chain (iron-sulfur protein and cytochrome c1). Zinc binds 3 times tighter to Fe-S-depleted bc1 complex indicating that the zinc binding site is not on the "Rieske" iron-sulfur protein in contrast to a recent report by Lorusso et al. (Lorusso, M., Cocco, T., Sardanella, A.M., Minuto, M., Bonomi, F., and Papa, S. (1991) Eur. J. Biochem. 197, 555-561). Zinc binds to a site which has the same affinity for zinc as for protons. We conclude that the zinc binding site is close to a protonatable group of the bc1 complex with pKa = 7.2 which has not been identified previously. We propose that this group is part of the proton channel at the hydroquinone oxidation center of the bc1 complex.

Animals↗

[Skeletal mineralization in cattle in 1960 and 1990 based on trephine biopsy data].

Skeleton of cows living in the zone of Kiev Polesye (Woodlands), a comparatively safe area of radioactive pollution, as compared with 1960, was found to have practically the same content of calcium, phosphorus, sodium, copper; the content of potassium decreased, that of zinc was greater; the increased content of magnesium, manganese, strontium and lead was statistically valid. An increased incorporation of magnesium, zinc and manganese and a decreased fixation of iron and potassium were mainly due to changed conditions of feeding and maintenance of the animals, while the increased content of strontium and lead was a result of the increased pollution of the environment.

Animals↗

Domain-structured N1,N2-derivatized hydrazines as inhibitors of ribonucleoside diphosphate reductase: redox-cycling considerations.

Eight analogues of 1-[5-halogenosalicylidene]-2-[2'-pyridinoyl]hydrazine and -[2'-pyridyl]hydrazine, four of 1-[pyridoxylidene]-2-[2'-pyridinoyl]hydrazine, seven of 1-[pyridoxylidene]-2-[2'-pyridyl]hydrazine, and one each of 1, 2-bis[pyridoxylidene]diaminoethane and bis[pyridoxylidenehydrazino]phthalazine were synthesized. Their solutions in DMF were assayed for activity against the metalloenzyme ribonucleoside diphosphate reductase (RdR), prepared from a subcutaneously growing murine tumor (sarcoma 180) implanted in B6D2F3 male mice. The 14C-labeled CDP reductase was assayed by the modified method of Takeda and Weber, in which [14C]cytidine was separated from deoxycytidine by thin-layer chromatography (TLC) on cellulose foil. Distribution of radioactivity was assessed with an automatic TLC linear analyzer. Of the 31 compounds tested, 13 were essentially inactive, 7 were highly active against RdR, and the remaining 20 were slightly more active than hydroxyurea (used as a reference compound). The mechanism of inhibition is discussed in terms of three alternative pathways, initiated by sequestration of iron embedded in the R1 subunit of the metalloenzyme to form a C-centered chelate radical (via redox cycling). Alternatively, the latter could either reduce the tyrosyl radical or intercept radicals generated in the reduction process.

Animals↗

Endothelial mediation is necessary for subsequent hepatocyte uptake of transferrin.

The authors previously have reported on the presence of transferrin (TF) receptors on liver endothelial cells and have shown that hepatic uptake of transferrin-iron (TF-Fe) complexes in the liver is mediated by the endothelium. We now provide evidence that this endothelial cell mediation may be necessary for hepatocyte uptake of TF-Fe complexes. Transport of TF-Fe from endothelial cell to hepatocyte was studied in mixed cell suspensions in which radiolabeled TF-Fe complexes were incubated at 37 degrees C with the two cell populations purified and then mixed in equal ratios. The mixtures were then refractionated at various times after incubation and cell-associated radioactivities measured. Radiolabeled TF was rapidly taken up by the endothelial cell fraction, but radioactivity began to decline in this fraction as it increased in the hepatocyte fraction. In double labeling experiments with 125I-TF-59Fe, both radiolabels moved across the endothelium in parallel fashion, indicating that Fe remains associated with TF during transcytosis. However, in hepatocytes the two radiolabels became dissociated, with Fe remaining cell-associated and TF being recycled. Hepatocyte uptake of processed TF was partially inhibitable by galactan and asialofetuin, indicating that hepatocyte uptake may occur via asialoglycoprotein receptors of hepatocyte.

Animals↗

Lead and iron absorption from rat small intestine: the effect of dietary Fe deficiency.

1. When lead is administered in drinking-water iron-deficient rats retain more Pb than Fe-replete rats (Six & Goyer, 1972; Klauder & Petering, 1975). In the present study the relationship between the absorption of Pb and Fe was investigated. 2. Adult male rats were transfered to a milk-based diet fed with or without supplementary Fe (180 mg Fe/kg as ferrous sulphate). After 7--9 d the absorption of duodenally-administered 203Pb and 59Fe was measured as uptake of radioactivity from the gastrointestinal tract after 90 min. 59Fe absorption was increased in rats given the unsupplemented diet for 7 d and was further increased in rats kept on the diet for up to 7 weeks. 203Pb absorption was not consistently increased by either short- or long-term Fe deprivation. 3. Much of the 203Pb in homogenates of the upper small intestine was bound to soluble protein of which up to 85% was dialysable. In contrast little 59Fe was dialysable. Only a small proportion of the soluble musosal Pb was associated with ferritin during gel-filtration chromatography although 203Pb precipitated together with carrier rat-liver ferritin with an antibody to rat-liver ferritin. 4. There appeared to be no direct relationship between the transfer of Fe and Pb across the small intestine of the adult rat.

Animals↗

Binding of manganese in human and rat plasma.

Albumin, transferrin and 'transmanganin' have all been proposed as the major Mn-binding ligand in plasma. The present investigations were initiated in order to resolve these discrepancies. Compared to other metals tested (109 Cd2+, 65Zn2+, 59Fe3+), 54Mn2+ bound poorly to purified albumin. The addition of exogenous albumin to plasma did not result in an increased 54Mn radioactivity associated with this protein. Also, incubation of 65Zn-albumin in the presence of excess Mn2+ (1 mM) did not result in the displacement of Zn from albumin or Mn binding. In contrast to these results, 54Mn was bound to purified transferrin, not as readily as Fe3+, but better than Zn2+ or Cd2+. Saturation of transferrin with Fe3+ (1.6 micrograms Fe/mg) prevented the binding of 54Mn indicating that Mn probably binds to Fe-binding sites on the protein. Polyacrylamide gel electrophoresis further demonstrated the association of 54Mn with transferrin rather than with albumin in both human and rat plasma. The amount of 54Mn radioactivity recovered with transferrin increased as incubation time was increased, probably due to oxidation of Mn2+ to Mn3+. Mn binding to transferrin reached a maximum within 5 and 12 h of incubation. About 50% of 54Mn migrated with transferrin, whereas only 5% was associated with albumin. A significant portion (20-55%) of the 54Mn radioactivity migrated with electrophoretically slow plasma components whose identity was not determined. Possibilities include alpha 2-macroglobulin, heavy gamma-globulins and/or heavy lipoproteins.

Animals↗

Effect of redox potential on fixation of 137Cs in lake sediment.

Fixation of 137Cs was determined in lake sediment suspensions under controlled redox potentials in the laboratory. The activity of previously added 137Cs on various clay sites was determined by time-series selective extractions. Monovalent cations, particularly NH+4, were much more effective at displacing 137Cs than divalent cations or Na+. Ammonium ion (NH+4) and Na+ were used to extract 137Cs from selective and non-selective 137Cs-binding sites, respectively. The activity of water-soluble 137Cs and Na-extractable 137Cs was significantly higher under anaerobic redox conditions (-200 mV), when soluble NH+4 concentrations in the anaerobic suspensions were 1000 microM or higher. Activities of 137Cs were highest (initially 40-50% of the 137Cs added) on the NH+4-extractable site. Over the long term, activities of NH+4-extractable 137Cs decreased linearly to below 10% as 137Cs was fixed on inter-lattice sites. Water-soluble 137Cs was significantly correlated with Na-extractable 137Cs in short-term experiments, suggesting the existence of an equilibrium between the different clay sites. High concentrations of NH+4 under anaerobic redox conditions could shift this equilibrium, resulting in increases in water-soluble 137Cs and increases in the activities of 137Cs bound on non-selective clay sites. Additional studies are necessary to evaluate the interaction of 137Cs with sulfides, iron oxides, and other reactive chemical species which may attenuate 137Cs in sediment.

Cesium Radioisotopes↗

Discovery of ancient silicate stardust in a meteorite.

We have discovered nine presolar silicate grains from the carbonaceous chondrite Acfer 094. Their anomalous oxygen isotopic compositions indicate formation in the atmospheres of evolved stars. Two grains are identified as pyroxene, two as olivine, one as a glass with embedded metal and sulfides (GEMS), and one as an Al-rich silicate. One grain is enriched in 26Mg, which is attributed to the radioactive decay of 26Al and provides information about mixing processes in the parent star. This discovery opens new means for studying stellar processes and conditions in various solar system environments.

Aluminum↗

Ocular changes in rabbits with corticosteroid-induced ocular hypertension.

Rabbit eyes with steroid-induced ocular hypertension were investigated in order to evaluate the histochemical abnormalities in the chamber angle region. The right eye of 14 rabbits was treated by dexamethasone 1% 3 times daily for 3 to 5 weeks. The eyes were stained by haematoxylin-eosin, periodic acid Schiff, fibrin, colloidal iron, and alcian blue with and without hyaluronidase. All treated eyes developed elevated intraocular pressure up to 4 weeks after treatment. These globes showed alcian-blue-positive hyaluronidase-sensitive staining in the amorphous material adjacent to Schlemm's canal and in the cytoplasmic granules of trabecular endothelial cells. There was no increase in incorporation of radioactive thymidine into nuclei of endothelial cells as seen by autoradiography. These results provide further support for the idea that there is abnormal accumulation of acid mucopolysaccharides in the chamber angle in steroid-induced ocular hypertension.

Animals↗

Metallic contamination of bone during drilling procedures.

The influence of drills and burs of different shapes and materials on the amount of metallic transfer was studied. In these experiments, holes were drilled in bone with radioactive tools and the amount of metal transferred to the bone was measured by means of gamma-ray spectrometry. The proportion of the drill material transferred to the bone varied widely, depending on the type of the drill, its previous usage, and on the specific element considered. Most of the drills transfer a few microgram of iron to the bone, together with smaller quantities of cobalt, tungsten, and chromium. The total quantity of material transferred to the bone from new drills exceeded that of old drills. Almost invariably, the second drilling transferred less material than did the first, even with used drills.

Animals↗

Non-specific binding of transferrin and lactoferrin to polystyrene culture tubes: role of the radioligand.

While evaluating the role of iron-binding glycoproteins on the in vitro uptake of 67Ga and 59Fe by tumor cells, it was observed that these radiometals bind to polystyrene culture tubes in the presence of transferrin or lactoferrin. The amount of 67Ga or 59Fe bound to the tube increases with glycoprotein concentrations up to 20 microgram/ml and decreases thereafter. This biphasic response is a reflection of metal-protein affinity and is greatest for 59Fe-lactoferrin. With 125I-labeled transferrin and lactoferrin, the amount of tube-bound radioactivity was inversely dependent on the glycoprotein concentration suggesting that glycoproteins bind to a limited number of binding sites on the tube wall. Approximately 10(13) glycoprotein molecules were bound per tube with an affinity constant of 1.89 X 10(7) 1/M for transferrin and 1.08 X 10(7) l/M for lactoferrin. These sites are not specific since addition of albumin inhibited the binding of radiolabeled glycoproteins to the tube. In the light of these observations, caution is required in interpreting results of cell culture experiments which have not directed attention to protein-plastic interaction.

Albumins↗

Aminoacids--precursors of melanin synthesis in hamster melanoma.

The role of L-tyrosine, L-phenylalanine, L-dihydroxyphenylalanine (dopa) and L-tryptophan in melanin biosynthesis in melanotic hamster melanoma IC-Sofia was investigated with the aid of 14C-aminoacids. Tyrosine and phenylalanine were found to be the main melanin precursors: about 64.5% of total melanin labeling was due to tyrosine incorporation and 27.4% to phenylalanine incorporation. Negligible proportions of melanin radioactivity (5.7% and 2.4%, respectively) resulted from dopa and tryptophan utilization in melanin synthesis. The involvement of each of the aminoacids under investigation in melanin synthesis in vivo is discussed.

Amino Acids↗

A bifunctional HBED-derivative for labeling of antibodies with 67Ga, 111In and 59Fe. Comparative biodistribution with 111In-DPTA and 131I-labeled antibodies in mice bearing antibody internalizing and non-internalizing tumors.

To investigate whether bifunctional ligands containing chelating structures other than EDTA and DTPA and metallic radiotracers other than 111In will reduce the non-specific radioactivity uptake in the liver during immunoscintigraphy, we synthetized an isothiocyanato-substituted phenolic polyaminocarboxylic acid (HBED-CI) for labeling of MAbs with 67Ga, 111In and 59Fe. Biodistribution of HBED-CI-labeled MAbs was compared to that of 131I and 111In-DTPA labeled MAbs in nude mice bearing tumors, which differ with regard to intracellular internalization and catabolism of the corresponding MAb-antigen complex. In the liver a continuous radioactivity excretion for 67Ga-HBED-CI-labeled MAbs was observed with kinetics that parallel 131I clearance after administration of 131I-MAbs, while 111In-HBED-CI-labeling led to a constant 111In liver level quite similar to that of 111In-DTPA-MAbs. In tumors, 67Ga-HBED-CI-MAb uptake again paralleled that of 131I-MAbs, showing continuous accumulation in tumor tissues when internalization of the MAb-antigen complex was not involved. A much lower uptake, which peaked between 24 and 48 h, was found in the case of MAb-antigen internalization. 111In of 111In-HBED-CI- and 111In-DTPA-labeled MAbs continuously accumulated in both types of tumors. Compared with 111In-DTPA-MAbs, an improvement in tumor-to-liver ratios, due to the reduced liver radioactivity associated with 67Ga-HBED-CI-labeled MAbs, could only be obtained with non-internalizing tumors. The time course of radioactivity distribution in the liver and in MAb-internalizing tumors after administration of 67Ga-HBED-CI-, 111In-HBED-CI- and 111In-DTPA-labeled MAbs further indicates a dominating influence of the metallic radiotracer rather than the ligand on retention or excretion of radioactivity in MAb-catabolizing tissues.

Animals↗

A study of the corrosion products of mild steel in high ionic strength brines.

The corrosion layer on steel surfaces that formed after exposure to waste isolation pilot plant (WIPP) brines under anoxic conditions was characterized for chemical composition, thickness and phase composition. The chemical composition of the corrosion layer was determined both by X-ray photoelectron spectroscopy (XPS) and by chemical analysis of acid solutions used to remove the corrosion layer. Atomic force microscopic (AFM) images indicated that the brine-corroded surface layer shows extensive granulation along the contours of the steel surface that is characteristic of sharp polishing marks. The corrosion layer seemed to be porous and could be dissolved and detached in dilute hydrochloric acid. The corrosion layer appears to be composed of iron oxides with some ionic substitutions from the brines. The 77 K Mössbauer spectrum recorded for iron powder leached under similar conditions indicated the corrosion layer was comprised principally of green rust.

Corrosion↗

Distribution of small- and medium-sized molecules within the genital tract of artificially inseminated gilts.

Radiolabelled compounds of different molecular size were used as tracers mixed with seminal plasma to investigate whether seminal plasma enters the oviducts of inseminated gilts. The substances were 125I-labelled human serum albumin for 3 gilts, 131I-labelled polyvinylpyrrolidone plus 59Fe citrate in 2 gilts and 131I-labelled human serum albumin plus 59Fe citrate in 2 gilts. The gilts were slaughtered 1 h after insemination and the radioactivity was measured in 4 parts of the oviduct, 9 parts of the uterine horns, the body of the uterus and the cervix. Different quantities of the compounds used were found in all oviducts, but there was close agreement between the distributions of the two compounds in the genital tract after simultaneous insemination. There was a difference (60-80%) in total amount of recovered radioactivity between left and right uterine horns. It is concluded that all compounds used entered the oviducts regardless of their molecular sizes.

Animals↗