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R J O'Connor

Publications and source records attributed to R J O'Connor.

17 recordsLinked to original sources
PubMed1992

Regeneration of functional hemoglobin from iron(III) hemoglobin by reduction with hydrogen and a heterogeneous catalyst.

Functional hemoglobin was regenerated from partially autoxidized hemoglobin by reduction with molecular hydrogen in the presence of a heterogeneous catalyst consisting of elemental platinum embedded in an electroactive polymer. The visible spectrum of the regenerated hemoglobin was identical to that of native iron(II) hemoglobin. The regenerated hemoglobin displayed highly cooperative oxygen-binding characteristics. P50 values for oxidized-regenerated hemoglobin samples were not different from native hemoglobin. The Hill coefficients for regenerated hemoglobin were slightly lower than the controls, possibly because of small amounts of irreversibly oxidized hemoglobin arising during the initial autoxidation. The advantages of the reduction system include: (1) the heterogeneous catalyst avoids the problem of protein adsorption onto bare platinum, (2) catalyst and reducing agent are easily removed from the protein, and (3) the by-product H+ is buffered easily.

Buffers↗
PubMed1991

The C-terminal 70 amino acids of the adenovirus E4-ORF6/7 protein are essential and sufficient for E2F complex formation.

E2F is a cellular transcription factor that binds to the adenovirus (Ad) E1A enhancer and E2aE promoter regions, to the cellular c-myc P2 and dihydrofolate reductase promoters, and to other viral and cellular regulatory regions. The binding activity of E2F to the Ad E2aE promoter is dramatically increased during an adenovirus infection (termed E2F induction). E2F induction is dependent on the expression of the 150 amino acid E4-ORF6/7 protein which forms a direct, physical complex with E2F to mediate the cooperative and stable binding of E2F to inverted sites in the E2aE promoter. Using in vitro DNA binding assays to measure the formation of the infection-specific complexes, we have defined the minimal domain of the E4-ORF6/7 protein, the C-terminal 70 amino acids, required to complex with E2F and stabilize its binding at the E2aE promoter. The ability of mutant E4-ORF6/7 proteins to form the stable E2F-E2aE promoter complex in vitro correlated well with their ability to trans-activate E2 transcription in vivo. These observations support a model in which the E4-ORF6/7 protein binds to E2F to induce the cooperative binding of two E2F molecules to the E2aE promoter thereby activating E2 transcription.

Adenovirus Early Proteins↗
PubMed1991

Substituent effects on the binding constants of arsenical-dithiol adducts.

Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to determine the relative binding constants for several arsenical-dithiol adducts. The compounds investigated were 2,3-dimercaptopropanol (British anti-lewisite; BAL), 1,2-ethane dithiol (ET), and 1,2-propane dithiol (PDT). It was found that PDT has a significantly higher affinity than ET or BAL for phenyldichloroarsine (PDA) in methanol.

Arsenicals↗
PubMed1987

One-dimensional and two-dimensional nuclear magnetic resonance studies of the reaction of phenyldichloroarsine with glutathione.

14C-labeled phenyldichloroarsine (PDA) enters the red blood cell and forms a 1:2 adduct with intracellular glutathione. Upon gel filtration of the hemolysate, [14C]PDA was recovered with the glutathione-containing fractions. One-dimensional and two-dimensional nuclear magnetic resonance spectroscopy were used to confirm the structure of the adduct and elucidate its stereochemistry, stability, and reactivity.

Arsenicals↗
PubMed1987

Caval tumor thrombus complicating renal cell carcinoma: a surgical challenge.

The surgical challenge of resection of renal cell carcinoma with vena caval invasion may require close cooperation between the urologist and cardiovascular surgeon. From 1977 to 1986, 13 patients with renal cell carcinoma and tumor thrombus invading the inferior vena cava (IVC) underwent radical surgical resection. In three of 13 patients the thrombus extended into the heart (right atrium two patients and right ventricle one patient). The tumor originated in the right kidney in 10 patients and in the left kidney in three patients. There were 10 men and three women with a mean age of 64 years (range, 46 to 75 years). Surgical management included midline incision, seven, with median sternotomy, four, and thoracoabdominal, two. After exposure of the renal vessels and IVC, all patients underwent radical nephrectomy. Two patients had caval sleeve resection, one had a partial caval resection, and seven had a 1 cm caval cuff. Planned cardiopulmonary bypass was used in three patients. The tumor thrombus was extracted by simultaneous atrial and caval approaches. One patient underwent unplanned emergency cardiopulmonary bypass after intraoperative cardiac arrest caused by a large tumor embolus of the pulmonary artery. No operative deaths occurred. Postoperative morbidity was significant in five of 13 patients, caval thrombosis in one, lower limb swelling in two, renal failure in one, and pulmonary edema in one patient. Two patients required long-term anticoagulation therapy for confirmed pulmonary emboli within 1 month of surgery. These complications resolved. The follow-up period ranged from 7 to 64 months with a mean of 36 months. Two patients died of metastatic disease at 24 and 48 months after surgery. Three patients are alive with metastatic disease at 6 to 64 months while one patient had a solitary metastatic lesion removed from the frontal lobe 4 years after nephrectomy and has been disease free a subsequent 18 months. Eight of 11 patients are disease free at 7 to 64 months (four patients greater than 52 months). Our 83% survival rate at a mean follow-up of 36 months suggests that this group of patients should not be denied aggressive resection. Documentation of tumor source and caval extension are essential to plan operative procedures, including use of cardiopulmonary bypass.

Aged↗
PubMed1979

Red cell membrane in hemolytic disease. Studies on variables affecting electrophoretic analysis.

Significant alterations in the spectrin: band 3 and band 4.1a: band 4.1b ratios and an occasional decrease in the peak height of band 4.2 with respect to band 4.1 were found in electrophoretic patterns of red cell membranes from patients with hereditary xerocytosis. Electrophoretic comparison of whole cell, cytoplasm and membrane polypeptides implied that atypical partitioning at hemolysis could account for some, but not all, of the alterations seen in membrane patterns of xerocytes. A decrease in band 4.2 peak height as well as a variation in the profile of band 3 were produced in controls by specific manipulations of the electrophoresis protocol. Metabolic depletion of normal cells produced the type of alterations in bands 3 and 4.1 found in xerocyte membranes, whereas Heinz body production, addition of calcium to the hemolysis buffer and incubation of membranes in detergent under conditions designed to promote proteolysis did not. The presence of a higher peak height of band 4.1b with respect to that of band 4.1a in membranes of patients with various other red cell disorders correlated with an increase in the percentage of reticulocytes in peripheral circulation. The appearance of both band 3 and 4.1 abnormalities in the patterns of control cells which had been enriched in young cells by density gradient centrifugation suggested that these alterations in hemolytic disease are related to the predominance of young cells in the population.

Adenosine Triphosphate↗
PubMedDate not supplied

Structure and dynamics of a lipoic acid-arsenical adduct.

The lipoic acid-phenyldichloroarsine adduct was prepared in methanol, and the structure and molecular motions of this adduct were studied. The results showed that a six-membered heteroatom adduct was formed. One-dimensional and two-dimensional NMR spectroscopy was used to confirm the structure and assign some of the resonances in the proton and carbon spectra. Spin-lattice relaxation times of the various carbon atoms indicated that the overall molecular reorientation time (tau R) of the molecule is 0.02 ns at 30 degrees C. An Arrhenius plot of the data showed that the activation energy (Ea) for molecular tumbling is 13.4 kJ/mol.

Arsenicals↗
PubMedDate not supplied

2,3-Dithioerythritol, a possible new arsenic antidote.

British antilewisite (2,3-dimercaptopropanol; BAL) has long been used as an arsenic antidote, but its therapeutic efficacy is limited by its inherent toxicity. We synthesized two less toxic derivatives of BAL and investigated their potential as antidotes to organic arsenic. The new compounds, 2,3-dithioerythritol (DTE) and 2,2-dimethyl-4-(hydroxymethyl)-1,3-dithiolane (isopropylidene derivative of BAL), react readily with phenyldichloroarsine (PDA) to yield the expected corresponding cyclic 1,3-dithioarsolanes. The BAL derivatives were compared to BAL in terms of their cytotoxicity and their ability to rescue PDA-poisoned mouse lymphoma cells in culture. The dithiolane was not a good antidote in the cultured cell system. In contrast, DTE was less toxic than BAL or DMSA and was superior at improving cell survival in PDA-exposed cells.

Animals↗
PubMedDate not supplied

Activation energies and formation rate constants for organic arsenical-antidote adducts as determined by dynamic NMR spectroscopy.

Phenyldichloroarsine reacts with 1,3-dimercapto-2-propanol and 1,2-dimercaptopropane to form 1:1 adducts in the form of a six-membered and five-membered heteroatom rings. Two geometric isomers for each compound are present in dynamic equilibrium. Rate constants and the activation barriers for the interconversion of the geometric isomers were determined by dynamic NMR spectroscopy. The activation barriers indicate that the five-membered heteroatom ring is more stable than the six-membered heteroatom ring.

Antidotes↗