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Biomedical subjects

C F Meares

Publications and source records attributed to C F Meares.

At least 127 records · Page 7Linked to original sources
PubMed1980

Evaluation of catheter thrombogenicity in vivo with indium-labeled platelets.

Platelets labeled with a lipid-soluble indium-111 8-hydroxyquinoline (oxine) complex were evaluated as an agent to measure the rate and degree of in vivo platelet accumulation on catheters. Polyethylene catheters and Teflon-coated guidewires were inserted into the femoral arteries or veins of dogs that had been injected with indium-labeled platelets. The catheters were passed to either the abdominal aorta or inferior vena cava and left in situ for 30 minutes to three hours. Images were obtained every five minutes with a gamma camera. This labeling technique is reproducible, allows multiple testing with a single preparation, and is relatively noninvasive. The results are easily quantitated to allow testing of different materials and coatings.

Animals↗
PubMed1979

Amphiphilic spectroscopic probes utilizing metal chelates.

The synthesis and initial applications are reported for 1-[p-(palmitamido)-phenyl]ethylenedinitrilotetraacetic acid. The results demonstrate the versatility of this spectroscopic probe molecule, which allows choice of a particular technique for a particular system as well as use of multiple spectroscopic techniques for complementary information about hydrophobic regions in biological systems.

Chelating Agents↗
PubMed1979

BLEDTA: tumor localization by a bleomycin analogue containing a metal-chelating group.

Two different Co(III) complexes of the antitumor antibiotic bleomycin have been prepared, and their in vivo distribution in mice has been investigated. The more thermodynamically stable of the Co(III)-bleomycin complexes has been modified by reaction with the bifunctional chelating agent 1-(p-bromoacetamidophenyl)ethylenedinitrilotetraacetic acid, to give a bleomycin derivative (BLEDTA) containing a powerful metal-chelating group. BLEDTA was radiolabeled with 111In(III) and its in vivo distribution in mice was examined. The potential of 111In-labeled BLEDTA as a tumor-visualizing agent was also investigated in humans with biopsy-proven cancers, predominantly (70%) squamous carcinoma of the head and neck. All of the 29 patients studied had at least one clinically proven site of the disease visualized with 111In-BLEDTA. These clinical results are significantly better than results we obtained in a comparable group of patients using directly labeled 111In-bleomycin and are similar to those reported by Nouel for 57Co-bleomycin [GANN Monogr. Cancer Res., 19, 301 (1976)].

Adult↗
PubMed1978

Indium-111-labeled autologous platelets for location of vascular thrombi in humans.

Twenty-two patients suspected of having either venous or arterial thrombi were studied with In-111-labeled autologous platelets. Whole-body scans were performed 3, 24, and 48 hr following i.v. injection. Twelve patients studied with saline-washed platelets had unsatisfactory 15-min recovery and biologic half-time. When the labeling was carried out in plasma, these values compared favorably with normal values reported for Cr-51-labeled autologous platelets. Of ten patients studied using platelets labeled in plasma, three had normal scans, six had abnormal scans, and one had an equivocal scan. All six abnormal scans were confirmed with corresponding positive findings in either the venogram, arteriogram, or lung scan. J Nucl Med 19: 626-634, 1978.

Adult↗
PubMed1977

Energy transfer between terbium and iron bound to transferrin: reinvestigation of the distance between metal-binding sites.

The addition of trivalent iron, gallium, and terbium ions to the metal binding sites of human transferrin has been investigated by fluorescence and spectrophotometric measurements. Results are consistent with the possibility that the addition of ferric nitrilotriacetate to apotransferrin does not lead to a random distribution of iron bound to the two metal-binding sites on the protein, but rather an asymmetric distribution with iron bound mainly to one of the sites. The subsequent addition of terbium leads to the binding of terbium ions to the vacant sites on monoferric transferrin molecules, and observations of the intensity of terbium fluorescence from such samples provides clear evidence of transfer of excitation energy from the terbium site to the iron site. These results lead to the estimate that the two metal-binding sites of human transferrin are separated by a distance of 25 +/- 2 A, in disagreement with an earlier report (Luk, C. K. (1971), Biochemistry 10, 2838) that the sites were separated by more than 43 A. Consideration of the dimensions of transferrin indicates that the two sites lie relatively close to each other on the macromolecule.

Apoproteins↗
PubMed1977

Interaction of anions with iron-transferrin-chelate complexes.

Preliminary evidence suggested that phosphate or borote destabilize iron-ovotransferrin-nitrilotriacetate complexes in the absence of added bicarbonate. The iron-ovotransferrin-EDTA complex was prepared in the absence of bicarbonate, and a number of anions, including phosphate, sulfate, and citrate, were found to perturb the visible absorbance (lambdamax = 490 nm) of this complex. Other anions, such as chloride, nitrate, and perchlorate, had little or no effect on the spectrum. Also, when bicarbonate was added to a solution of the iron-transferrin-EDTA complex (A515 = 0.45), within 2 min, the visible absorbance had decreased to A515 = 0.13. Slowly a new peak appeared (lambdamax = 470 nm), evidently the iron-transferrin-CO3 complex. When these spectral changes were monitored in detail, the lack of an isosbestic point indicated the existence of one or more intermediates in the conversion of iron-transferrin-EDTA complex to the iron-transferrin-CO3 complex. Experiments using ternary complexes containing either 59Fe or [14C]EDTA show that both iron and EDTA nearly completely dissociate from the protein (most likely concomitantly within 2 min after bicarbonate is added. These observations are best explained by a paradigm which includes anion binding to the apoprotein. It is clear that there is an intimate relationship between anions and the binding of iron chelates by transferrin.

Bicarbonates↗
PubMed1977

Zinc is associated with the beta subunit of DNA-dependent RNA polymerase of Bacillus subtilis.

The Bacillus subtilis DNA-dependent RNA polymerase holoenzyme and core enzyme each contain approximately two atoms of zinc per molecule. When the dissociated subunits of the enzyme are passed through a blue dextran-Sepharose affinity column, only the beta subunit binds to the column. The total zinc content of the enzyme is tightly bound to the beta subunit. Dialysis studies suggest that the two zinc ions differ in the strength of their association with the beta subunit. The presence of zinc in beta is consistent with several other lines of evidence which indicate that this subunit is dirrectly involved in phosphodiester bond formation. The blue dextran-Sepharose column procedure should be useful in future studies of the dissociation and reassociation of the enzyme since the method is rapid and provides excellent recovery of the beta subunit as well as the alpha and beta' subunits of the RNA polymerase.

Bacillus subtilis↗
PubMed1976

Radiolabeled antitumor agents.

Bleomycin serves as a useful prototype for a study of the various properties required in a radiopharmaceutical for tumor imaging. Both in vitro and in vivo results using bleomycin labeled with a large number of different radionuclides have now been reported. In general, it has not been possible to predict in vivo biologic behavior solely from in vitro data. For example, 57Co-bleomycin and 111In-bleomycin both have identical patterns in several different chromatographic systems and do not break down with prolonged storage in saline, exposure to heat, or other cations. However, when the labeled bleomycin is exposed to serum transferrin (and to other as yet unidentified ligands in the body) a difference in stability becomes obvious. The stability and biologic activity of 57Co-bleomycin in humans demonstrate the validity of metal chelation as a labeling technique for this specific molecule, and also suggests that other stable chelates will have useful applications. Although 57Co-bleomycin has the most desirable biologic characteristics of all the chelates of bleomycin, the extremely long physical half-life of 57Co of 270 days creates a significant contamination problem in the hospital. Because of this, the use of 57Co-bleomycin is limited to a few specialized centers. All users have emphasized the need for a better radionuclide to produce a labeled bleomycin with the same or superior biologic characteristics to 57Co-bleomycin. Unfortunately, the elements forming the most stable chelates with bleomycin (copper, zinc, cobalt, and nickel) do not have radionuclides with suitable physical characteristics for scanning. Copper-67 may become available in the future from high-energy linear accelerators. However, even if it were available, copper will probably not have as good chemical properties as cobalt.

Abdominal Neoplasms↗
PubMed1976

Covalent attachment of metal chelates to proteins:the stability in vivo and in vitro of the conjugate of albumin with a chelate of 111indium.

Human serum albumin has been conjugated to 1-(p-bnezenediazonium)-(ethylenedinitrilo)tetraacetic acid, a powerful chelating agent, and radioactive 111indium ions have been added specifically to the chelating groups. The product, with a specific radioactivity of about 1 mCi/mg of protein, was employed as a radiotracer in scintillation scanning studies with human volunteers. Results show that 48 hr after injection, practically all of the label remains attached to albumin. This is confirmed by electrophoresis of serum proteins; 7 days after injection, 85% of the radioactivity in the serum is still in the albumin fraction. These observations agree with in vitro studies of the labeled albumin in human serum, where loss of the metal ion from the chelating group to the protein transferrin amounts to less than 3% after 1 week and less than 5% after 2 weeks. Measurements of the distribution of label in mice up to 23 days after injection suggest that metabolism of the labeled protein does not lead to binding of indium ions by transferrin. The binding of indium and other metal ions by transferrin has previously posed a major impediment to the use of metal chelates for in vivo diagnostic procedures. Demonstration of the kinetic inertness of the chelate in these experiments suggests the use of related chelates as physical probes of biological systems.

Animals↗
PubMed1975

Bifunctional chelates for radio-pharmaceutical labeling.

The use of the first of a new class of chelating agents for the binding of metal ions to macromolecules as a novel approach to radiopharmaceutical labeling is described. Advantages are mild reaction conditions, large variety of accessible radionuclides and reactive groups, and separation of synthetic organic chemistry from radiochemistry. Human serum albumin and bovine fibrinogen labeled with 111Indium using this technique were relatively stable in vitro and in vivo, showed little alteration in function, and have potential as tumor localizing agents in humans.

Animals↗
PubMed1972

Perturbed angular correlation study of a haptenic molecule.

The angular correlation of the 173-247 keV gamma-ray cascade after the electron-capture decay of (111)In is strongly perturbed when the 1-p-nitrophenyl-ethylenediaminetetraacetate chelate of (111)In(8+) is added to a solution containing rabbit antibody to dinitrophenyl groups. The radioactive chelate can be displaced by the addition of dinitrophenyllysine or unlabeled chelate. The average association constant between the antibody and the labeled chelate has been estimated from perturbed angular correlation measurements; this value is compared to the results of equilibrium dialysis. These experiments provide good evidence that information concerning macromolecular behavior can be obtained from perturbed angular correlation experiments that use chemically specific labels.

Journal Article↗