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Biomedical subjects

S W Edwards

Publications and source records attributed to S W Edwards.

At least 91 records · Page 5Linked to original sources
PubMed1991

Activation of the neutrophil myeloperoxidase-H2O2 system by synovial fluid isolated from patients with rheumatoid arthritis.

Synovial fluid isolated from 16 patients with rheumatoid arthritis activated luminol dependent chemiluminescence in bloodstream neutrophils, and the maximal activity stimulated varied over a 50-fold range. In contrast, these same fluids only activated a much lower range (two- to threefold) of maximal rates of lucigenin dependent chemiluminescence and cytochrome c reduction, two assays which only measure oxidant secretion which is independent of myeloperoxidase. Over 95% of the luminol dependent chemiluminescence activated by all samples was inhibited by azide (indicating its dependence upon myeloperoxidase), but anti-(myeloperoxidase) IgG (which specifically inhibits only the extracellular activity of this enzyme) only inhibited the response stimulated by some samples: those fluids which activated the highest luminol dependent chemiluminescence also stimulated the greatest activity of an extracellular myeloperoxidase-H2O2 system. A clear correlation was shown to exist between the activity of myeloperoxidase already present in the fluids (after its secretion from neutrophils in situ within the rheumatoid joint) and the ability of the fluid to activate luminol dependent chemiluminescence. It is concluded, therefore, that all synovial fluid samples tested possess almost equivalent levels of a factor(s) which activated O2-/H2O2 secretion and that the variations in the measured activity of the extracellular myeloperoxidase-H2O2 system are dependent upon the level of degranulation which had occurred within the joint.

Acridines↗
PubMed1991

Effects of recombinant human granulocyte colony-stimulating factor on neutrophil function in vitro and in vivo following chemotherapy and autologous bone marrow transplantation.

Recombinant granulocyte colony-stimulating factor (rG-CSF) primed the ability of human neutrophils to generate increased levels of reactive oxidants in response to fMet-Leu-Phe, and also resulted in an increased rate of protein biosynthesis which was similar to that induced by granulocyte-macrophage colony-stimulating factor. However, rG-CSF reduced the chemotactic activity of neutrophils in response to endotoxin and did not result in an enhanced rate of killing of Staphylococcus aureus. rG-CSF was administered to patients after high dose chemotherapy and autologous bone marrow transplantation for the treatment of either Hodgkin's disease or multiple myeloma. This cytokine decreased the period of neutropenia following such treatment. Neutrophil function in two patients, measured seven days after the final administration of rG-CSF, was severely impaired as indicated by a greatly decreased ability to generate reactive oxidants. However, seven days later (i.e. 14 days post-therapy), the functional activity of the neutrophils from these patients had returned to normal. These data indicate that assays of neutrophil function together with morphological assessment of neutrophil numbers and maturity should be performed in order to evaluate the immune status of patients undergoing such therapy.

Bone Marrow Transplantation↗
PubMed1991

Influence of two levels of caffeine on maximal torque at selected angular velocities.

The purpose of this study was to determine the effect of two doses of caffeine on peak torque and muscle endurance in the knee extensors and flexors. Twenty males and 16 females were randomly assigned to one of three groups: 600 mg caffeine, 300 mg caffeine, or a control receiving a placebo. Subjects with similar caffeine consumption history were used and all subjects abstained from caffeine usage for 24 hours prior to testing. Subjects were tested for maximal strength and endurance at 75, 180, and 300 degrees per second using a Cybex II Isokinetic Dynomometer interfaced with a Cybex Data Reduction Computer. After pretesting, each subject was given one of three solutions using a double-blind design. Following a one hour rest and absorption period, the subjects were again tested. Data were analyzed using a 3 x 2 repeated measures analysis of variance with a grouping factor at three levels (600 mg vs 300 mg vs 0 mg) and a trial factor at two levels (pre- vs posttest). The following variables were analyzed at all angular velocities: peak torque and subsequent joint angle, peak torque at 30 degrees, and peak torque at 70 degrees. At 300 degrees per second, the dependent variables were total torque for 15 repetitions, total torque for the first 3 repetitions, and total torque for the last 3 repetitions. The results indicated no significant changes from pre- to posttest. It was concluded that maximal strength and endurance was not affected by the two levels of caffeine used in this study and that caffeine may not be considered an ergogenic aid in strength output in subjects naive to resistance training.

Adult↗
PubMed1990

Receptor expression and oxidase activity in human neutrophils: regulation by granulocyte-macrophage colony-stimulating factor and dependence upon protein biosynthesis.

Incubation of human bloodstream neutrophils with 50 u/ml recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) "primed" the respiratory burst (as assessed by fMet-Leu-Phe stimulated luminol-dependent chemiluminescence) and resulted in a rapid (within 15 min) up-regulation of expression of CD11b and CD18 (as measured by FACS analysis). This rapid "priming" and modulation of receptor expression was not inhibited by cycloheximide and hence appeared to be independent of de novo protein biosynthesis. When neutrophils were incubated for up to 5 h in culture, the fluorescence distributions of CD11b and CD18 declined indicating the loss of expression of these receptors as the neutrophils aged, but in rGM-CSF treated suspensions receptor expression was maintained. When neutrophils were incubated in the presence of cycloheximide, they progressively lost their ability to generate reactive oxidants in response to fMet-Leu-Phe so that by 5 h incubation with this inhibitor they could only generate about 25% of the oxidative response stimulated in untreated cells, and the expression of CD16 and CD18 was grossly impaired. Similar effects were observed in rGM-CSF treated suspensions except that cycloheximide required longer incubation times (typically 4-5 h) before impairment of function or receptor expression occurred. These data show that de novo protein biosynthesis is required for both the maintenance of neutrophil function and also for the continued expression of some plasma membrane receptors.

Antigens, CD↗
PubMed1990

Effects of ingested doses of caffeine on neuromuscular reflex response time in man.

To determine the effect of two doses of caffeine on a caudal (monosynaptic) reflex in humans, 30 subjects were randomly assigned to one of three groups. The groups received one of the following doses of caffeine per kilogram body weight using a double blind, placebo controlled design: 6 mg/kg, 3 mg/kg or a placebo. All of the subjects were similarly caffeine naive and were instructed to fast eight hours, refrain from caffeine for 96 hours, and avoid strenuous exercise 48 hours prior to testing. At the pre-test and post-test all subjects were given three trials of the patellar ligament reflex. Following pre-testing, subjects ingested either the caffeine solutions or an inert solution. After a one hour absorption period, subjects were post-tested. Gain scores were analyzed using a one-way ANOVA among the three groups, and a Newman-Keuls multiple range test was used to compare the three groups. The analysis revealed a significant difference in the gain score of the 6 mg/kg group. The control group had a mean gain of 4.3 msec, the 3 mg/kg group had a mean gain of 11.5 msec, and the 6 mg/kg group had a mean gain of 23.8 msec. Although the 6 mg/kg group was significantly different than the other two groups, a visible but nonsignificant difference was found between the 6 mg and 3 mg groups and the 3 mg and 0 mg groups. It was concluded that a 6 mg/kg dose of caffeine significantly lengthens reflex time in college age students.

Adult↗
PubMed1990

Inhibition of neutrophil superoxide secretion by the preservative, methylhydroxybenzoate: effects mediated by perturbation of intracellular Ca2+?

The preservative, methylhydroxybenzoate inhibited O2- secretion from human neutrophils activated by both the chemotactic peptide fMet-Leu-Phe and phorbol myristate acetate (PMA): the low level of oxidant secretion activated by the ionophore A23187 was similarly reduced in preservative-treated suspensions. Oxidant secretion was similarly reduced in fMet-Leu-Phe and A23187 treated suspensions in which intracellular Ca2+ was buffered by loading with Quin-2, indicating that methylhydroxybenzoate may exert its effects by perturbation of intracellular Ca2(+)-dependent processes. Methylhydroxybenzoate could mimic EGTA in preventing the Ca2+ dependent enhancement of trypsin activity and could also bind this cation in experiments using a Ca2+ electrode, although the preservative bound Ca2+ more slowly and had a lower affinity than EGTA. These data indicate that methylhydroxybenzoate may exert its effects on neutrophils by perturbation of Ca2(+)-dependent activation pathways and this phenomenon may also explain its other known pharmacological effects. Furthermore, these observations provide an insight into the mechanisms by which intracellular Ca2+ may regulate oxidant secretion.

Calcium↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor (GM-CSF) primes the respiratory burst and stimulates protein biosynthesis in human neutrophils.

Pre-treatment of human neutrophils with rGM-CSF resulted in a 3-fold increase in the rate of fMet-Leu-Phe stimulated reactive oxidant generation, as assessed by luminol- and lucigenin-chemiluminescence and O2- secretion. When blood-stream neutrophils were incubated in RPMI 1640 medium supplemented with [35S]methionine, both fMet-Leu-Phe (0.1 microM) and gamma-interferon (100 U/ml) stimulated a 3-4-fold increased incorporation of label into TCA-precipitable material. Similarly, rGM-CSF (50 U/ml) also stimulated protein biosynthesis in bloodstream neutrophils, and newly labelled polypeptides were separated by two-dimensional polyacrylamide gel electrophoresis. Two classes of polypeptides were visualised on these gels: the relative rate of labelling of one class changed very little upon rGM-CSF treatment whereas the relative rate of labelling of a second group increased 3-12-fold.

Colony-Stimulating Factors↗
PubMed1989

Stimulation of protein synthesis in human neutrophils by gamma-interferon.

Treatment of human, peripheral blood neutrophils with gamma-interferon both "primed" their ability to generate reactive oxidants and increased their rate of protein synthesis. This increased rate of protein synthesis was greatest 60 min after the addition of 100 U/ml gamma-interferon and was not due to an increased intracellular pool of radiolabelled amino acid. Analysis of the newly-synthesized polypeptides by two-dimensional polyacrylamide gel electrophoresis (PAGE) revealed two classes of proteins which were regulated by this agent. The first of these represented proteins whose rate of labelling increased very little (1-2-fold) whereas the rate of biosynthesis of a second group of proteins increased more markedly (10-20-fold). We propose that these newly-synthesized, gamma-interferon regulated proteins play an important role in the function of these cells during an acute inflammatory response.

Blood Proteins↗
PubMed1989

Inhibition of myeloperoxidase by salicylhydroxamic acid.

Salicylhydroxamic acid inhibited the luminol-dependent chemiluminescence of human neutrophils stimulated by phorbol 12-myristate 13-acetate or the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe). This compound had no inhibitory effect on the kinetics of O2.- generation or O2 uptake during the respiratory burst, but inhibited both the peroxidative activity of purified myeloperoxidase and the chemiluminescence generated by a cell-free myeloperoxidase/H2O2 system. The concentration of salicylhydroxamic acid necessary for complete inhibition of myeloperoxidase activity was 30-50 microM (I50 values of 3-5 microM) compared with the non-specific inhibitor NaN3, which exhibited maximal inhibition at 100-200 microM (I50 values of 30-50 microM). Whereas taurine inhibited the luminol chemiluminescence of an H2O2/HOC1 system by HOC1 scavenging, this compound had little effect on myeloperoxidase/H2O2-dependent luminol chemiluminescence; in contrast, 10 microM-salicylhydroxamic acid did not quench HOC1 significantly but greatly diminished myeloperoxidase/H2O2-dependent luminol chemiluminescence, indicating that its effects on myeloperoxidase chemiluminescence were largely due to peroxidase inhibition rather than non-specific HOC1 scavenging. Salicylhydroxamic acid prevented the formation of myeloperoxidase Compound II, but only at low H2O2 concentrations, suggesting that it may compete for the H2O2-binding site on the enzyme. These data suggest that salicylhydroxamic acid may be used as a potent inhibitor to delineate the function of myeloperoxidase in neutrophil-mediated inflammatory events.

Humans↗
PubMed1989

Body surface potential mapping to monitor the effects of thrombolytic therapy following acute myocardial infarction.

The authors demonstrate the value of body surface potential mapping (BSPM) and a limited lead system in monitoring complete ECG evolution following myocardial infarction (MI) and the effects of thrombolytic therapy. They produced ST-segment isopotential maps, which indicate the site and extent of myocardial injury. Pathological Q wave maps were also produced, which intimate the extent of myocardial necrosis. Analysis of a sequence of maps recorded during the acute phase of MI revealed sudden changes attributed to reperfusion, reinfarction or "silent" events.

Adult↗
PubMed1989

Role of myeloperoxidase in the killing of Staphylococcus aureus by human neutrophils: studies with the myeloperoxidase inhibitor salicylhydroxamic acid.

We have used salicylhydroxamic acid (SHAM) to inhibit intraphagosomal myeloperoxidase activity in order to evaluate the role of this enzyme in the killing of Staphylococcus aureus by human neutrophils. 50 microM-SHAM reduced the luminol-dependent chemiluminescence response stimulated during phagocytosis of unopsonized latex beads and opsonized S. aureus by over 80% and 60%, respectively. When opsonized S. aureus were incubated with neutrophils, 45% were killed within 15 min incubation and 60% by 1 h. However, in neutrophil suspensions incubated with 50 microM-SHAM, only 13% were killed by 15 min whilst 71% still remained viable after 1 h. This inhibitor had no effect upon the number of bacteria phagocytosed or upon degranulation. In a cell-free system, 2.5 microM-H2O2 alone killed 55% of the bacteria, whereas in the presence of myeloperoxidase (i.e. 10 mU myeloperoxidase and 2.5 microM-H2O2) virtually all of the bacteria were killed: the addition of 50 microM-SHAM abolished this myeloperoxidase-enhanced killing but did not affect the H2O2-dependent killing. We therefore conclude that in normal neutrophils whilst H2O2 is required for killing of this pathogen, both myeloperoxidase-dependent and -independent pathways exist.

Cell Degranulation↗
PubMed1989

Role of myeloperoxidase in intracellular and extracellular chemiluminescence of neutrophils.

Activated polymorphonuclear leucocytes (neutrophils) can generate both intracellular and extracellular luminol dependent chemiluminescence. As luminol dependent chemiluminescence largely measures the activity of the myeloperoxidase-H2O2 system, and as the extracellular activity of this enzyme may be responsible for the tissue damage associated with inflammatory conditions such as rheumatoid arthritis, the aim of this work was to distinguish between intracellular and extracellular chemiluminescence so that the extracellular activity of this enzyme could be evaluated. Azide was used as a non-specific inhibitor of both intracellular and extracellular chemiluminescence, whereas anti-(human myeloperoxidase) IgG was used to inhibit specifically the extracellular activity of myeloperoxidase. Thus this IgG is a useful analytical tool for studying the extracellular activity of the myeloperoxidase-H2O2 system in the pathology of rheumatoid arthritis.

Azides↗
PubMed1989

Age of initiation and switching patterns between smokeless tobacco and cigarettes among college students in the United States.

A stratified, random, multi-stage, cluster sample of physical activity classes among 72 colleges and universities throughout the United States yielded 5,894 usable responses (males = 2,888); (females = 3,006). Twenty-three per cent of the students who began smoking before the age of 10 were current smokers, while 61 per cent of those who began using smokeless tobacco before the age of 10 were current smokeless tobacco users. College students were more likely to switch from smokeless tobacco to cigarettes than from smoking cigarettes to smokeless tobacco.

Adolescent↗
PubMed1988

Immunological detection of myeloperoxidase in synovial fluid from patients with rheumatoid arthritis.

We have used rocket immunoelectrophoresis and immunoblotting to detect myeloperoxidase in synovial fluid from patients with rheumatoid arthritis. This protein was enzymatically inactive but its identity as myeloperoxidase was confirmed by comparing its subunit structure with that of the purified enzyme. When neutrophils were stimulated to secrete myeloperoxidase in vitro, a polypeptide with an apparent molecular mass of 62 kDa was detected extracellularly by immunoblotting. Neutrophils isolated from synovial fluid showed a reduced level of this 62 kDa polypeptide but it was detected extracellularly in synovial fluid by immunoblotting. Thus, we conclude that neutrophils in synovial fluid from patients with rheumatoid arthritis have been activated in vivo to secrete myeloperoxidase and propose that the products of this enzyme system can contribute to the tissue damage associated with this disease.

Arthritis, Rheumatoid↗
PubMed1988

The relationship between superoxide generation, cytochrome b and oxygen in activated neutrophils.

The O2 affinity for O2.- generation (i.e. O2 tension at which 50% of the O2-saturated activity was observed) by rat neutrophils activated by the chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine) plus cytochalasin B was measured as 5.4 microM (+/- 1.4, n = 5). Similarly, the O2 tension at which cytochrome b was oxidized to 50% of its aerobic steady-state level in activated cells was 4.7 microM (+/- 1.0, n = 3): in non-activated cells the corresponding value for cytochrome b oxidation was 11.4 microM (+/- 2.8, n = 3). It is proposed that O2 depletion at inflammatory sites may limit oxidant generation by activated neutrophils and thus reduce oxidant damage to surrounding tissues.

Animals↗
PubMed1988

Gamma interferon enhances the killing of Staphylococcus aureus by human neutrophils.

The effect of purified human interferon-gamma on the responsiveness of human neutrophils was investigated. Pre-incubation of neutrophils with 100 U interferon ml-1 for 10 min at 37 degrees C resulted in a 2.5-fold increase in N-formylmethionyl-leucyl-phenylalanine-stimulated reactive oxygen metabolite generation (as assayed by luminol-dependent chemiluminescence). Pre-treatment of neutrophils with interferon also potentiated their ability to kill Staphylococcus aureus, and thus it is proposed that this lymphokine may also enhance neutrophil function in vivo under certain pathological conditions.

Interferon-gamma↗
PubMed1988

Effect of ingestion of smokeless tobacco on motor distal latency of the median nerve.

Subjects were 17 men between the ages of 18 and 32 yr. and regular users of smokeless tobacco. Each subject received three treatments consisting of one pouch of Skoal Bandits, one pinch of their regular brand, and a nonnicotine piece of chewing gum. The nervous transmission at the neuromuscular junction in the right thumb was compared before treatment and once every minute for 15 min. after treatment. Repeated-measures analysis of variance indicated a significant increase in the distal latencies for both the brand-name grouping and in the regularly used brand. No such difference was found in a control group when compared to the pretest results. It was concluded that smokeless tobacco ingestion resulted in a delay in the nervous transmission across the neuromuscular junction. This delay was hypothesized to be caused by the enduring binding action of nicotine to the acetylcholine receptor sites, thereby blocking the impulse in some of the faster conducting nerve fibers.

Adolescent↗