Garry J | Oxford University Press (original) (raw)

Papers by Garry J

Journal of The American College of Cardiology, 1993

The objective of this investigation was to evaluate the changes in parasympathetic tone associate... more The objective of this investigation was to evaluate the changes in parasympathetic tone associated with long-term angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure. Angiotensin-converting enzyme inhibitors provide hemodynamic and symptomatic benefit and are associated with improved survival in patients with congestive heart failure. Angiotensin II, whose production is ultimately inhibited by these agents, exerts significant regulatory influence on a variety of target organs including the central and peripheral nervous systems. Accordingly, it would be anticipated that angiotensin-converting enzyme inhibitors would significantly alter the autonomic imbalance characteristic of patients with congestive heart failure and that this influence over neural mechanisms of cardiovascular control may significantly contribute to the hemodynamic benefit and improved survival associated with angiotensin-converting enzyme inhibitor therapy. In the current investigation, changes in autonomic tone associated with long-term administration of an angiotensin-converting enzyme inhibitor were measured using spectral analysis of heart rate variability in 13 patients with congestive heart failure who were enrolled in a double-blind randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor zofenopril. Both placebo and treatment groups were balanced at baseline study in terms of functional class, ventricular performance and autonomic tone. After 12 weeks of therapy with placebo, there was no change in total heart rate variability, parasympathetically governed high frequency heart rate variability or sympathetically influenced low frequency heart rate variability. In contrast, therapy with zofenopril was associated with a 50% increase in total heart rate variability (p = 0.09) and a significant (p = 0.03) twofold increase in high frequency heart rate variability, indicating a significant augmentation of parasympathetic tone. These results demonstrate that long-term treatment of patients having congestive heart failure with an angiotensin-converting enzyme inhibitor is associated with a restoration of autonomic balance, which derives in part from a sustained augmentation of parasympathetic tone. Such augmentation of vagal tone is known to be protective against malignant ventricular arrhythmias in patients with ischemic heart disease and therefore may have similar benefit in the setting of ventricular failure, thus contributing to the improved survival associated with angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure.

Free Radical Biology and Medicine, 1991

The anticarcinogenic action of carotenoids such as beta-carotene has been frequently ascribed to ... more The anticarcinogenic action of carotenoids such as beta-carotene has been frequently ascribed to their antioxidant properties. However, very little is actually known about the nature of the antioxidant reaction or the products that are formed. beta-Carotene was exposed to either spontaneous autoxidation conditions or to radical-initiated autoxidation conditions. The products were separated by reverse-phase HPLC, and individual peaks were characterized with an on-line diode array detector. Carbonyl products were isolated and characterized by several procedures, including borohydride reduction to the corresponding alcohols, derivatization with O-ethyl-hydroxylamine to the corresponding O-ethyl-oximes of the carbonyls, and analysis by GC-MS. Under the conditions of the experiments, the formation of a homologous series of carbonyl products was demonstrated, including beta-apo-13-carotenone, retinal, beta-apo-14'-carotenal, beta-apo-12'-carotenal, and beta-apo-10'-carotenal. Several very hydrophobic compounds were formed, which have not been previously identified. In addition, the products of NaOCl-treatment of beta-carotene were analyzed, and shown to be significantly different from the autoxidation products. This type of product analysis should be useful in determining the nature of the oxidants reacting with beta-carotene in vivo.

Journal of Endodontics, 2000

The purpose of this study was to analyze the type and frequency of defects in nickel-titanium rot... more The purpose of this study was to analyze the type and frequency of defects in nickel-titanium rotary endodontic files after routine clinical use, and to draw conclusions regarding the reasons for failure. All of the files (total: 378, Quantec Series 2000) discarded after normal use from a specialist endodontic practice over 6 months were analyzed. Almost 50% of the files showed some visible defect; 21% were fractured and 28% showed other defects without fracture. Fractured files could be divided into two groups according to the characteristics of the defects observed. Torsional fracture occurred in 55.7% of all fractured files, whereas flexural fatigue occurred in 44.3%. The results indicated that torsional failure, which may be caused by using too much apical force during instrumentation, occurred more frequently than flexural fatigue, which may result from use in curved canals.

Biofactors, 1997

Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and... more Lipoic acid (thiotic acid) is being used as a dietary supplement, and as a therapeutic agent, and is reported to have beneficial effects in disorders associated with oxidative stress, but its mechanism of action remains unclear. We present evidence that lipoic acid induces a substantial increase in cellular reduced glutathione in cultured human Jurkat T cells, human erythrocytes, C6 glial cells, NB41A3 neuroblastoma cells, and peripheral blood lymphocytes. The effect depends on metabolic reduction of lipoic acid to dihydrolipoic acid. Dihydrolipoic acid is released into the culture medium where it reduces cystine. Cysteine thus formed is readily taken up by the neutral amino acid transport system and utilized for glutathione synthesis. By this mechanism lipoic acid enables cystine to bypass the χ-c transport system, which is weakly expressed in lymphocytes and inhibited by glutamate. Thereby lipoic acid enables the key enzyme of glutathione synthesis, γ-glutamylcysteine synthetase, which is regulated by uptake-limited cysteine supply, to work at optimum conditions. Flow cytometric analysis of freshly prepared human peripheral blood lymphocytes, using monobromobimane labeling of cellular thiols, reveals that lipoic acid acts mainly to normalize a subpopulation of cells severely compromised in thiol status rather than to increase thiol content beyond physiological levels. Hence lipoic acid may have clinical relevance in restoration of severely glutathione deficient cells.

Freshwater Biology, 1994

1. Abiotic disturbances strongly modify spatial and temporal patterns of lotic ecosystem communit... more 1. Abiotic disturbances strongly modify spatial and temporal patterns of lotic ecosystem community structure and function. Such effects are produced because disturbances alter organic matter, nutrient and contaminant dynamics and the distribution and abundance of bacterial, algal, macroinvertebrate and fish communities.2. River ice break-up is a seasonal disturbance in rivers at high altitudes and latitudes world-wide and is characterized, in part, by large increases in current velocity, stage, water temperature, concentrations of suspended materials and substrate scouring.3. These abiotic factors are likely to have important effects on primary producers, consumers, and food-web dynamics of river biota. Despite the potential importance of river ice break-up on community structure and function, detailed information describing the magnitude of their effects and underlying causal mechanisms is scarce.4. The objective of this paper is to provide a hydrological and ecological review and perspective on the potential effects of ice break-up on lotic ecosystems. Specifically, the potential importance of break-up on water temperature, river sediments and geomorphology, riverine energy sources, contaminants, and its effects on river biota and food-web dynamics are evaluated.

Kidney International, 2001

interventions to decrease oxidative stress and associated in-Elevated plasma F2-isoprostanes in p... more interventions to decrease oxidative stress and associated in-Elevated plasma F2-isoprostanes in patients on long-term hemoflammation. dialysis

Biochemical Pharmacology, 1996

Nitric oxide (NO) is produced in physiological and pathophysiological conditions by three distinc... more Nitric oxide (NO) is produced in physiological and pathophysiological conditions by three distinct isoforms of NO synthase (NOS): endothelial NOS (ecNOS), inducible NOS (iNOS), and brain NOS (bNOS). Selective inhibition of iNOS may be beneficial in various forms of shock and inflammation, whereas inhibition of bNOS may protect against neuroinjury. This article surveys the enzymatic mechanism of NO production, lists the strategies and pharmacological tools for selective inhibition of distinct NOS isoforms, and considers the side-effects of the various approaches. Selective inhibition of NOS isoforms is achieved by: (a) targeting the differential co-factor (calmodulin or tetrahydrobiopterin) requirement of various NOS isoforms, and NOS; (b) targeting the differential substrate requirements of cells expressing various isoforms of NOS (L-arginine uptake blockers or arginase); (c) the use of pharmacological agents that are selectively taken up by cells expressing various isoforms of NOS (7-nitroindazole); or (d) developing pharmacological NOS inhibitors with isoform specificity. The amino acid-based NOS inhibitor, NG-nitro-L-arginine, shows a preference for ecNOS and bNOS over iNOS, whereas L-N6-(1-iminoethyl)lysine is selective for iNOS over bNOS. Certain non-amino acid-based small molecules, such as aminoguanidine and certain S-alkylated isothioureas, also express selectivity towards iNOS and have anti-inflammatory and anti-shock properties. 7-nitroindazole, a bNOS-selective inhibitor, protects in central nervous system injury. Clearly, there are a number of distinct approaches that are worthy of further research efforts in order to achieve even more selective targeting of various NOS isoforms

Lipids, 1979

High levels of dietary fat have been shown to promote the development of mammary tumors induced i... more High levels of dietary fat have been shown to promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(α)anthracene, and polyunsaturated fats were found to be more effective than saturated fats. In further studies it was found that diets containing 3% sunflowerseed oil (polyunsaturated fat) and 17% beef tallow or coconut oil (saturated fats) enhance tumorigenesis as much as a diet containing 20% sunflowerseed oil. Rats on these diets developed at least twice as many tumors as those fed diets containing either 3% sunflowerseed oil or 20% of the saturated fats alone. These results are in accord with human epidemiological data which show that breast cancer mortality in different countries is positively correlated with total fat intake but not with intake of polyunsaturated fat. Total fat intake varies greatly in different countries, but most human diets probably contain levels of polyunsaturated fat at least equivalent to 3% sunflowerseed oil.

Trends in Biochemical Sciences, 1987

... RJ (1985)Proc NatlAtad Set USA 82 7237-7241 27 Tweten RK Barb~en JT and Colher RJ (1985)J Bto... more ... RJ (1985)Proc NatlAtad Set USA 82 7237-7241 27 Tweten RK Barb~en JT and Colher RJ (1985)J Btol Chem 260 10 ... van Kuijk, Alex Sevanian, Garry J. Handelman and Edward A. Dratz Recen@ a was discovered that phosphohpase A2 preferennally hydrolyses perott&zed fall ...

Biochemical and Biophysical Research Communications, 1992

A tool is any physical item that can be used to achieve a goal, especially if the item is not con... more A tool is any physical item that can be used to achieve a goal, especially if the item is not consumed in the process. Informally the word is also used to describe a procedure or process with a specific purpose.