Papers by Michael McCormick
Elsevier Ocean Engineering Series, 2001
Archives of Biochemistry and Biophysics, May 15, 2002
We set out to identify whether HOCl, which is generated from H 2 O 2 /MPO/Cl À , is a proximal me... more We set out to identify whether HOCl, which is generated from H 2 O 2 /MPO/Cl À , is a proximal mediator of H 2 O 2 programmed cell death in the HL-60 human leukemia cell. We found that authentic HOCl induces apoptosis in the HL-60 cell. Both the addition of methionine, an HOCl scavenger, and the removal of Cl À from the medium to prevent the formation of HOCl inhibited H 2 O 2 -induced apoptosis. HL-60 cells underwent apoptosis when exposed to HOCl in full medium, which gives rise to chloramines by the reaction of HOCl with amine groups, but not by HOCl in the amine-free HBSS, in which HOCl but not chloramines can be detected. Authentic chloramines induced apoptosis in this cell line in a concentration-dependent manner and at concentrations lower than HOCl. Full medium exposed to HOCl for 24 h would support methionine noninhibitable apoptosis, but did not react with 2-nitro-5-thiobenzoic acid (TNB), raising the possibility that the final inducer is a nonoxidant formed from HOCl and chloramines. We conclude that the signal for apoptosis induced by H 2 O 2 in the MPO-containing HL-60 cell involves the reaction of the diffusible oxidant HOCl with amines producing chloramines and a subsequent non-TNB-reactive product. Ó
J Biol Chem, 1998
Phagocytes secrete the heme protein myeloperoxidase, which is present and active in human atheros... more Phagocytes secrete the heme protein myeloperoxidase, which is present and active in human atherosclerotic tissue. These cells also generate hydrogen peroxide (H2O2), thereby allowing myeloperoxidase to generate a range of oxidizing intermediates and stable end products. When this system acts on L-tyrosine in vitro, it forms o, o'-dityrosine, which is enriched in atherosclerotic lesions. Myeloperoxidase, therefore, may oxidize artery wall proteins in vivo, cross-linking their L-tyrosine residues. In these studies, we used electron paramagnetic resonance (EPR) spectroscopy to identify an oxidizing intermediate in this reaction pathway and in parallel reactions catalyzed by horseradish peroxidase and lactoperoxidase. Using an EPR flow system to rapidly mix and examine solutions containing horseradish peroxidase, H2O2, and L-tyrosine, we detected free tyrosyl radical (a2,6H = 6.3 G, a3,5H = 1.6 G, and abetaH = 15. 0 G). We then used spin trapping techniques with 2-methyl-2-nitrosopropane (MNP) to further identify this intermediate. The resulting three-line spectrum (aN = 15.6 G) was consistent with an MNP/tyrosyl radical spin adduct. Additional MNP spin trapping studies with ring-labeled L-[13C6]tyrosine yielded a characteristic eight-line EPR spectrum (aN = 15.6 G, a13C (2) = 8.0 G, a13C (1) = 7.1 G, a13C (1) = 1.3 G), indicating that the MNP adduct resulted from trapping a carbon-centered radical located on the aromatic ring of L-tyrosine. This same eight-line spectrum was observed when human myeloperoxidase or bovine lactoperoxidase was substituted for horseradish peroxidase. Furthermore, a partially immobilized MNP/tyrosyl radical spin adduct was detected when we exposed a synthetic polypeptide composed of glutamate and L-tyrosine residues to the myeloperoxidase-H2O2-L-tyrosine system. The broadened EPR signal resulting from this MNP/polypeptide adduct was greatly narrowed by proteolytic digestion with Pronase, confirming that the initial spin-trapped radical was protein-bound. Collectively, these results indicate that peroxidases use H2O2 to convert L-tyrosine to free tyrosyl radical. They also support the idea that free tyrosyl radical initiates cross-linking of L-tyrosine residues in proteins. We suggest that this pathway may play an important role in protein and lipid oxidation at sites of inflammation and in atherosclerotic lesions.
Data Revues 00029149 V88i1 S000291490101579x, Mar 9, 2011
Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow... more Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four-to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 2 1 ⁄2 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5-and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two-to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention. ᮊ2001 by
Laterality Asymmetries of Body Brain and Cognition, Oct 25, 2012
In this paper we report the outcomes of two attempts to correlate the Zenhausern Preference Quest... more In this paper we report the outcomes of two attempts to correlate the Zenhausern Preference Questionnaire (PT) with the Polarity Questionnaire (PQ). Across two laboratories we consistently found no correlation between these two scales. Our findings are consistent with a previous attempt to validate the PQ (Genovese, 2005). We conclude that researchers attempting to use the PQ should take note of this validity question.
Experimental Biology and Medicine, Jun 1, 2004
Vessel dilator and kaliuretic hormone, two cardiovascular peptide hormones, enhance urine flow 2-... more Vessel dilator and kaliuretic hormone, two cardiovascular peptide hormones, enhance urine flow 2-to 13-fold and 4-fold, respectively, in persons with class III New York Heart Association congestive heart failure (CHF). The natriuresis and diuresis secondary to vessel dilator and kaliuretic hormone are not blunted as are atrial natriuretic peptide and brain natriuretic peptide effects in persons with CHF compared with healthy individuals. The present investigation determined if the two peptide hormones that do not have blunted effects in persons with CHF may have added beneficial effects when given simultaneously to individuals with class III CHF. Together with each at 100 ng/kg of body weight per minute, vessel dilator and kaliuretic hormone increased urine flow rate 3.5-fold (P , 0.05) compared with their 60-min baseline and control CHF subjects' urine flow rates. Combined, they enhanced the excretion rate of sodium a maximum of 3.6-fold (P , 0.05) with 2.5-and 2-fold enhancement 2 and 3 hrs after infusion. These data indicate that vessel dilator and kaliuretic hormone have diuretic and natriuretic effects when used in combination, but these effects are not additive over their individual effects in persons with CHF.
Kidney Int, 1999
antioxidant enzyme activities but also inhibited increases seen Unilateral ureteral obstruction i... more antioxidant enzyme activities but also inhibited increases seen Unilateral ureteral obstruction impairs renal antioxidant enwith sodium depletion. We conclude that suppression of renal zyme activation during sodium depletion.
Marine Technology Society Journal, 1999
ABSTRACT
J Soc Psychol, 1980
Summary The research investigated the search and decision-making processes of dyadic groups confr... more Summary The research investigated the search and decision-making processes of dyadic groups confronted with a nonprogrammed decision-making task. The purpose of the study was to determine if dyads would follow search and decision-making processes ...
Chemical research in toxicology, May 23, 2016
Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, a... more Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, and the dietary supplementation of zinc has proven protective in those cases. 3,3',4,4',5-Pentachlorobiphenyl (PCB126), a liver toxicant, alters hepatic nutrient homeostasis and lowers hepatic zinc levels. The current study was designed to determine the mitigative potential of dietary zinc in the toxicity associated with PCB126 and the role of zinc in that toxicity. Male Sprague-Dawley rats were divided into three dietary groups and fed diets deficient in zinc (7 ppm Zn), adequate in zinc (30 ppm Zn), and supplemented in zinc (300 ppm). The animals were maintained for 3 weeks on these diets, then given a single IP injection of vehicle or 1 or 5 μmol/kg PCB126. After 2 weeks, the animals were euthanized. Dietary zinc increased the level of ROS, the activity of CuZnSOD, and the expression of metallothionein but decreased the levels of hepatic manganese. PCB126 exposed rats exhibited...
Qjm Monthly Journal of the Association of Physicians, Apr 1, 2008
Background: Intravenous alteplase is licensed for treatment of ischaemic stroke within 3 h of ons... more Background: Intravenous alteplase is licensed for treatment of ischaemic stroke within 3 h of onset. Up to one-third of patients in the UK present to hospital within this time window but few are treated. Aims: To examine the effect of a stroke thrombolysis protocol on service provision for an acute stroke service in the UK, jointly run by Neurology and Medicine for the Elderly providing a comprehensive stroke service to a local population of 370 000. Design: Prospective observational study. Methods: Data collected prospectively for all thrombolysis referrals over a 12-month period beginning July 2004.
Free Radical Biology and Medicine, Jul 1, 2003
The interaction of two clinically important anticancer agents doxorubicin (DXR) and daunorubicin ... more The interaction of two clinically important anticancer agents doxorubicin (DXR) and daunorubicin (DNR) and the DNR analog 5-iminodaunorubicin (5IDNR) with the model mammalian peroxidase microperoxidase 11 (MP11) and H 2 O 2 has been investigated using spectrophotometric and EPR techniques. We demonstrate that DNR, DXR, and 5IDNR undergo irreversible oxidation by MP11/H 2 O 2 , forming colorless products in both phosphate buffer pH 7.0 and in phosphate buffer pH 7.0/MeOH mixture (1:1 vol/vol), suggesting an extensive modification of the compounds' chromophores. The initial rate of the anthracyclines' oxidation is independent of anthracycline concentrations, but is linearly dependent on [H 2 O 2 ] i at constant [MP11] i (and vice versa), indicating that the reaction is zero order in [anthracycline], first order with respect to [H 2 O 2 ] and [MP11], and second order overall. Based on data obtained using DNR, DXR, 5IDNR, and p-hydroquinone k 2app , the apparent second order rate constant for the formation of a reactive intermediate from MP11 and H 2 O 2 (an analog of peroxidase compound I) has been determined to be in the range of (2.51-5.11) ϫ 10 3 M Ϫ1 s Ϫ1 in both solvent systems. EPR studies show that oxidation of DNR, DXR, or 5IDNR with MP11/H 2 O 2 generates free radicals, suggesting that the reaction may be a one-electron process. This study also shows that 5IDNR, but not DNR or DXR, efficiently protects MP11 heme against degradation by H 2 O 2 . Our overall conclusion is that MP11 is an effective catalyst of oxidation of anthracyclines by H 2 O 2 . Given that, at sites of inflammation or cancer, the anthracyclines can colocalize with peroxidases, protein degradation products, and with H 2 O 2 , peroxidation could be one possible fate of these anticancer agents in vivo.
Journal of Biological Chemistry, 1996
The iron chelator deferoxamine (Desferal; DSFL) reacts with peroxidases and H2O2 to form the DSFL... more The iron chelator deferoxamine (Desferal; DSFL) reacts with peroxidases and H2O2 to form the DSFL radical (DSFL.), which can be detected by EPR spectroscopy. We have found that DSFL. formation resulting from exposure to H2O2 and any of a number of different peroxidases is greatly enhanced in the presence of the nitrone spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN). This enhancement was seen at 4-POBN concentrations as low as 200 microM. We observed a modest enhancement of DSFL. formation with 2-methyl-2-nitrosopropane. However, no enhancement was seen with 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) or phenyl-tert-butylnitrone. A modest enhancement was also seen with the nitrone compound pyridine N-oxide. 2-Methyl-2-nitrosopropane and pyridine N-oxide were additionally capable of increasing enzymatic peroxidase activity as measured by o-dianisidine and/or tetramethylbenzidine oxidation. Furthermore, at high concentrations of 4-POBN (50 mM) in the absence of DSFL, we detected a peroxidase/H2O2-dependent 12-line EPR spectrum that likely represents a 4-POBN/.4-POBN nitrogen-centered spin adduct. In the presence of both 4-POBN (10 mM) and DMPO (100 mM), an 18-line EPR spectrum was observed consistent with formation of a DMPO/.4-POBN nitrogen-centered spin adduct. Thus, the nitrone spin trap 4-POBN can enhance the peroxidase-mediated formation of DSFL., possibly via the formation of a transient 4-POBN radical species. These data suggest the importance of assessing the potential for nitrone spin traps to both inhibit and enhance biological oxidation prior to their use as potential pharmacological agents.
The American Journal of the Medical Sciences, Nov 1, 1995
Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126 amino acid ANF proho... more Atrial natriuretic factor (ANF), consisting of amino acids 99-126 of the 126 amino acid ANF prohormone, increases cyclic guanosine monophosphate (GMP) (thought to be the mediator of its physiologic effects) in plasma and urine of human subjects. Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide, consisting of amino acid 1-30, 31-67, and 79-98, respectively, of this same prohormone have natriuretic, diuretic, kaliuretic, and blood pressure lowering properties in humans. These three new peptide hormones increase cyclic GMP in vitro but were never investigated to determine whether they also cause extrusion of cyclic GMP from cells, resulting in an increase of cyclic GMP in plasma and/or urine. Infusion of each of these peptide hormones at their 100 ng/kg body weight/min concentrations for 60 minutes into healthy humans resulted in a sevenfold increase in cyclic GMP in plasma and urine secondary to ANF, but no significant increase secondary to the other atrial peptide hormones. Based on the current data, ANF has a unique effect on the metabolism of cyclic GMP, causing it to be extruded from the cell, whereas the other three atrial peptides represent the more classical metabolism of cyclic GMP via cyclic GMP phophodiesterases.
Redox biology, 2016
Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV... more Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10μM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2(•-) and H2O2, which correlated with increased levels of MnSOD activity and immuno-reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96h indicating that as the cells became more differentiate...
We present a laser plasma triggered jet experiment where we produce millimeter-scale collimated o... more We present a laser plasma triggered jet experiment where we produce millimeter-scale collimated outflows from a cylindrically symmetric electrode configuration motivated by astrophysical jet dynamics. The electrode design consists of a grounded plane with a ˜1 cm diameter hole and a wire aligned normally to this plane, with its tip placed at the center of the hole. A rapid discharge is formed between the wire and ground plane when a laser pulse hits an aluminum target placed above the electrodes, creating plasma which closes the circuit. The resulting current and corresponding magnetic fields give rise to a plasma jet. The jets were 0.1-0.3 cm wide, about 2 cm in length, had velocities of ˜40 km/s and an estimated plasma density of less than 10^17 cm-3. To study the effects of magnetic fields on jet evolution, we have embedded the plasma in axially directed permanent magnetic fields with strength up to 0.4 Tesla. We measured the evolution of the jet over duration of ˜1 μs with nanosecond resolution using a fast ICCD camera and interferometry. Under certain conditions the jets also form helical structures due to kink instabilities and the onset is characterized. We compare the dynamics of the plasma jet with one dimensional MHD codes.
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Papers by Michael McCormick