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Biomedical subjects

A J Baker

Publications and source records attributed to A J Baker.

At least 109 records · Page 6Linked to original sources
PubMed1993

Investigation of factors affecting fluorometric quantitation of cytosolic [Ca2+] in perfused hearts.

The goal of these studies was to examine the effects of several factors that may artifactually influence quantitation of cytosolic [Ca2+], [Ca2+]c, while using the fluorescent calcium indicator Indo-1. The following factors were investigated: 1) a possible fluorescence contribution from unhydrolized Indo-1/AM (by Mn2+ quenching), 2) Ca2+ buffering by Indo-1 (by varying [Indo-1]), 3) endothelial and mitochondrial Indo-1 loading (by bradykinin stimulation and calculations), and 4) effects of changing tissue fluorescence (predominantly NAD(P)H) on calculated [Ca2+]c during hypoxia (by a new method which allowed simultaneous determination of [Ca2+]c and changes in [NAD(P)H]). No significant contribution of Indo-1/AM was found. With increasing [Indo-1], calculated systolic [Ca2+]c fell significantly. Indo-1 incorporation (< 18%) into endothelial cells, caused a slight underestimation of systolic [Ca2+]c, while mitochondrial Indo-1 loading may cause overestimation of [Ca2+]c. With increased tissue fluorescence, during hypoxia, systolic [Ca2+]c may be underestimated by approximately 27% (for Indo-1 loading factors three to five times original tissue fluorescence). These studies suggest conditions in which experimental artifacts could be minimized to allow reliable quantitation of [Ca2+]c in intact perfused hearts using Indo-1 fluorometry. The major problem of obtaining reliable results depended on the ability to correct for changing NAD(P)H fluorescence while keeping [Indo-1] low.

Animals↗
PubMed1993

Intracellular tetanic calcium signals are reduced in fatigue of whole skeletal muscle.

Force and intracellular calcium signals were monitored in whole bullfrog semitendinosus muscles during fatigue produced by intermittent tetanic stimulation. Intracellular calcium signals were monitored using the fluorescent calcium-sensitive indicator indo-1 from the ratio of fluorescence intensities (R) at 400 and 470 nm. Fatiguing stimulation caused 1) proportional decreases of tetanic force and R, suggesting a component of the decreased force during fatigue of whole muscle may be due to insufficient calcium to activate contraction; 2) a progressive slowing of the relaxation of both force and R, suggesting slowed force relaxation may be mediated by slowed calcium removal from the myoplasm; 3) an increase of resting level R, suggesting impaired calcium removal from, or increased leakage to the cytosol; 4) prolongation of the twitch contraction, which was paralleled by changes in R. These findings are consistent with previous single fiber studies and suggest that changes in whole muscle contractility with fatigue may be partially mediated by changes in calcium handling by the cell.

Animals↗
PubMed1993

Slow force recovery after long-duration exercise: metabolic and activation factors in muscle fatigue.

To investigate the roles of metabolic and nonmetabolic factors in human muscle fatigue, two relatively brief nonexhausting exercise protocols that produced similar levels of moderate fatigue were used: short-duration exercise (SDE; 2-min sustained maximal voluntary contraction) and long-duration exercise (LDE; 15- to 20-min intermittent exercise). After exercise and during recovery, multiple potential mechanisms of fatigue were studied from measurements of voluntary, twitch, and tetanic forces; intracellular metabolites (using 31P-nuclear magnetic resonance spectroscopy); and electromyographic signals. The major findings were as follows. 1) After SDE, fatigue closely correlated with increased [Pi]. Both force and [Pi] recovered within approximately 5 min after exercise. 2) After LDE, force recovered slowly, with significant fatigue beyond 15 min after exercise; however, recovery of [Pi] was not slowed. 3) Electromyographic signals were little affected by either protocol. These findings suggest that multiple mechanisms contribute to moderate fatigue. Fatigue from SDE may arise primarily from metabolic mechanisms, whereas fatigue from LDE involves an additional slowly recovering nonmetabolic mechanism that may arise from impaired activation, beyond the cell membrane, at the level of excitation contraction-coupling.

Adult↗
PubMed1993

Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans.

Evidence from models of traumatic brain injury implicates excitotoxicity as an integral process in the ultimate neuronal damage that follows. Concentrations of the excitatory amino acid glutamate were serially measured in the cerebrospinal fluid (CSF) of patients with traumatic brain injuries and in control patients for comparison. The purpose of the study was to determine whether glutamate concentrations were significantly elevated following traumatic brain injury and, if so, whether they were elevated in a time frame that would allow the use of antagonist therapy. Cerebrospinal fluid was sampled fresh from ventricular drains every 12 hours and analyzed using high-performance liquid chromatography for the excitatory amino acids. The peak concentrations of glutamate in the CSF of the 12 brain-injured patients ranged from 14 to 474 microM and were significantly higher than those in the three control patients, 4.9 to 17 microM (Mann-Whitney U-test, p < 0.02). Glutamate concentrations in five of the eight patients who were still being sampled on Day 3 were beyond the control group range. The implication of this study is that severely head-injured patients are exposed to high concentrations of a neurotoxic amino acid for days following injury and thus may benefit from antagonist intervention.

Adolescent↗
PubMed1992

Effect of cyclic adenosine monophosphate, 5'-(N-ethylcarboxyamido)-adenosine and methylxanthines on the release of thromboxane and lysosomal enzymes from human alveolar macrophages and peripheral blood monocytes in vitro.

We have investigated the effect of the manipulation of intracellular cyclic adenosine monophosphate (cyclic AMP) and the stimulation of adenosine receptors on the function of human alveolar macrophages in vitro. Human alveolar macrophages harvested by bronchoalveolar lavage were stimulated by opsonised zymosan 1 mg/ml in the presence of N6,2'0-dibutyryladenosine 3':5' cyclic monophosphate (dibutyryl cyclic AMP) 5 x 10(-6) to 5 x 10(-3) M,8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cyclic AMP) 5 x 10(-6) to 5 x 10(-3) M, 5'-(N-ethylcarboxamido)-adenosine (NECA) 10(-7) to 10(-4) M, adenosine 10(-7) to 10(-4) M, theophylline 5 x 10(-6) to 5 x 10(-3) M and enprofylline 5 x 10(-8) to 5 x 10(-4) M. The subsequent release of thromboxane B2 (TXB2) and N-acetyl-beta-D-glucosaminidase (NAG) activity was monitored. In addition, the release of TXB2 and NAG from zymosan stimulated human monocytes incubated in the presence of NECA 10(-7) to 10(-4) M was measured. The TXB2 release from alveolar macrophages were inhibited by dibutyryl cyclic AMP and 8-bromo cyclic AMP and to a lesser extent by NECA, theophylline and enprofylline. However, adenosine had no effect. None of the agents studied altered NAG release. In addition, monocytes showed greater sensitivity to the inhibitory effects of 5-N-ethylcarboxamido adenosine than alveolar macrophages. In conclusion, the alveolar macrophage was inhibited by stable analogues of cyclic AMP and xanthines at supratherapeutic concentrations but have no functional excitatory adenosine receptors and only a residual inhibitory adenosine receptor function compared to the precursor monocyte.

Acetylglucosaminidase↗
PubMed1992

Influence of human muscle length on energy transduction studied by 31P-NMR.

Muscle contractions at lengths below the optimum for force development were previously found to cause less fatigue than contractions at the optimum length (Lo). Decreased fatigability was suggested to arise from fewer cross-bridge interactions in shortened sarcomeres. In the present study, this suggestion was tested by monitoring energy use of human ankle dorsiflexor muscles during and after contractions at Lo and shortened lengths (Ls) with phosphorus nuclear magnetic resonance spectroscopy. The nuclear magnetic resonance spectra indicated similar rates of ATP use during contractions at Lo and Ls. Phosphocreatine, at an initial concentration of 37 mM, was reduced to an equivalent extent by 2 min of ischemic exercise at Lo (to 2.3 mM) and Ls (to 4.7 mM). Changes in pH (indicating glycolytic ATP production) were also equivalent at Lo and Ls. Exercise caused pH to fall from an initial level of 7.07 to 6.5 at Lo and to 6.53 at Ls. In relation to previous experiments performed under similar conditions on human ankle dorsiflexor muscles, the present experiments suggest that in shortened muscle the decreased force found in this and previous studies and the decreased fatigability that was previously found may not be simply due to fewer cross-bridge interactions in shortened sarcomeres. Examination of the relationships between developed force and levels of metabolites suggests that changes of force during fatigue and recovery correlate better with intracellular [Pi] and H2PO4- than with [H+].

Adenosine Triphosphate↗
PubMed1992

In vivo and in vitro effects of glucocorticosteroids on arachidonic acid metabolism and monocyte function in nonasthmatic humans.

Glucocorticosteroids are used as anti-inflammatory agents in a range of diseases, however, their mechanism of action is unknown. Recently, inhibition of arachidonic acid metabolism has been suggested as one possible mechanism of action. A series of experiments were undertaken in nonasthmatic humans to examine the effects of oral prednisolone and dexamethasone and inhaled budesonide on the excretion of the urinary leukotriene E4 (LTE4), an established marker of total body leukotriene generation in vivo. In addition, the effect of the drugs on the in vitro and ex-vivo function of monocytes was examined. In vitro dexamethasone greater than 10(-8) M inhibited the thromboxane A2 (TxA2) release from human monocytes, an effect which recovered within 24 h. In vivo, neither inhaled budesonide (1.6 mg.day-1 for 7 days), nor a standard therapeutic dose of oral prednisolone (30 mg.day-1 for 3 days), nor high doses of oral dexamethasone (8 mg.day-1 for 2 days) altered the excretion of urinary LTE4, despite the latter completely suppressing endogenous cortisol production. The ex-vivo zymosan stimulated release of TxA2 release from monocytes was not altered by the standard dose prednisolone, but was reduced by high dose dexamethasone and inhaled budesonide. This study shows that high doses of systemic steroids have little effect on arachidonic acid metabolism in normal nonasthmatic humans. Inhaled budesonide, however, does reduce arachidonic acid metabolism in circulating monocytes, presumably by affecting these cells during their passage through the lung.

Administration, Topical↗
PubMed1992

Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study.

To determine whether pulsatile hypothermic perfusion with University of Wisconsin preservation solution is superior to topical cooling as a method for the preservation of amputated limbs, six pairs of amputated canine limbs were preserved for twelve to fifteen hours. One limb of each pair was subjected to topical cooling and the other, to pulsatile hypothermic perfusion with University of Wisconsin solution. The bioenergetic status of the limbs was monitored by 31phosphorus magnetic-resonance spectroscopy, and histological evaluation was performed to assess ischemic changes in the preserved tissue. The pH and tissue levels of adenosine triphosphate declined three times more slowly in the limbs that were preserved by pulsatile hypothermic perfusion than in the topically cooled limbs. Consistent with these findings, the perfused limbs also had less histological evidence of ischemic injury. The data from this in vitro study show that pulsatile hypothermic perfusion with University of Wisconsin solution, in combination with an optimum degree of topical cooling, is superior to topical cooling alone as a method of preserving the bioenergetic status of amputated limbs.

Adenosine↗
PubMed1991

Changes in extracellular concentrations of glutamate, aspartate, glycine, dopamine, serotonin, and dopamine metabolites after transient global ischemia in the rabbit brain.

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Hypothermia prevents ischemia-induced increases in hippocampal glycine concentrations in rabbits.

We subjected 10 New Zealand White rabbits to 10 minutes of global cerebral ischemia under either normothermic (37 degrees C) or moderately hypothermic (29 degrees C) conditions. Hippocampal concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. Outcome was assessed by both neurological and neuropathologic criteria. Hypothermia afforded nearly complete protection from ischemic injury. Ischemia-induced increases in the concentrations of glutamate, aspartate, and glycine in the normothermic group (3, 12, and 3 times baseline) were strikingly attenuated in the hypothermic group. In addition, the prolonged postischemic elevation of glycine levels seen in the normothermic group was absent in the hypothermic group. These results suggest that the neuroprotective properties of hypothermia may reside, in part, in their ability to prevent increases in the extracellular concentrations of amino acids that enhance the activity of the N-methyl-D-aspartate receptor complex.

Animals↗
PubMed1991

Fatigue and myalgia in AIDS patients.

Fatigue and myalgia are common in patients with acquired immunodeficiency syndrome (AIDS). To determine whether altered muscle metabolism or impaired activation of muscle might account for these symptoms, we utilized three different exercise protocols to produce fatigue in nine AIDS patients who complained of both fatigue and exercise-exacerbated myalgia. Five were taking azidothymidine (AZT), which may cause a mitochondrial myopathy. Simultaneous measures of force, EMG, and muscle metabolites (phosphocreatine, inorganic phosphate, adenosine triphosphate, and intracellular pH) using phosphorus nuclear magnetic resonance spectroscopy were performed during fatigue and recovery. There were no significant differences between patients and controls in terms of fatigability, muscle metabolism, or muscle activation. These results provide no support for the hypothesis that fatigue or myalgia in AIDS patients derives from altered muscle metabolism or that AZT produces mitochondrial myopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability.

We examined the relationships between muscle force and both phosphate and hydrogen ion concentrations in muscles with differential fatigability and in different types of exercise. We measured force and 31phosphorus nuclear magnetic resonance spectra from the tibialis anterior (a slow-contracting, fatigue resistant, postural leg muscle) during a sustained maximum contraction (anaerobic exercise) and during intermittent contractions (aerobic exercise). We observed similar relationships between the decline in muscle force during fatigue and changes in both phosphate and hydrogen ion concentrations during both aerobic and anaerobic exercise in tibialis anterior. Furthermore, these relationships were similar to those previously observed in the adductor pollicis. The demonstration of constant relationships between muscle contraction force and metabolism under different exercise conditions and in muscles of different function supports the view that both phosphate and hydrogen ions are important regulatory factors in the fatigue of human muscle.

Adenosine Triphosphate↗
PubMed1989

Investigations of muscle bioenergetics with 31P NMR.

Many factors have been proposed to contribute to the development of muscle fatigue, but as yet a definitive assessment of their relative contributions has not been possible. To determine whether changes in bioenergetic factors are determinants of muscle force during the development of fatigue, simultaneous measurements were made during fatiguing exercise of the decline in muscle force and changes in phosphorus (31P) nuclear magnetic resonance (NMR) spectra. The results showed that the decline in force strongly correlated with a rise in inorganic phosphate (Pi) concentration; in contrast, fatigue correlated less strongly with intracellular pH. Similar results were found in different muscles and with different exercise protocols. They suggest that the rise in [Pi] is a mechanism that produces progressive inhibition of the force-generating reaction, while energy availability is not limiting. Down-regulation of force and energy utilization are consistent with fatigue being not simply a disruptive process, but an adaptive response that establishes an equilibrium between energy supply and demand.

Adenosine Triphosphate↗
PubMed1988

Human alveolar macrophage activation: inhibition by forskolin but not beta-adrenoceptor stimulation or phosphodiesterase inhibition.

Alveolar macrophages are the most numerous cells within human airways. They release inflammatory mediators following immunological challenge and have been implicated in the pathogenesis of asthma. beta-agonists and phosphodiesterase inhibitors are frequently used in the treatment of asthma and are potent inhibitors of human mast cells. We have examined the role of the beta-agonist, isoprenaline, the phosphodiesterase inhibitor Ro-20 1724, and the adenylate cyclase stimulator forskolin on the activation of human alveolar macrophages. This was assessed by monitoring the release of thromboxane B2 (TXB2), leukotriene B4, N-acetyl-beta-D-glucosaminidase (NAG), and superoxide (SO) following stimulation of the cells by opsonised zymosan or IgE/anti IgE complexes. Neither isoprenaline (1nM-10 microM) nor Ro-20 1724 (0.5-50 microM) alone or in combination had any inhibitory effect on release of these mediators. However, forskolin (0.1-100 microM) significantly inhibited release of both TXB2 and SO but not NAG. This result shows that human alveolar macrophages do not possess functional beta-receptors, although stimulation of adenylate cyclase with forskolin, inhibits some of the elements of macrophage activation.

Adrenergic beta-Agonists↗
PubMed1987

Training on selected self-management techniques and the generalization and maintenance of interpersonal skills for registered nurse students.

This study examined the effects of training on selected self-management procedures (post-workshop practice, self-monitoring, self-assessment, and self-reinforcement) on the generalization and maintenance of interpersonal skills with a group of registered nurse students. The findings indicate that those self-management procedures enabled the student nurses to maintain a positive attitude toward the use of interpersonal skills in their work and maintain their skill level over a period of time significantly better than a control group who received interpersonal skills training only. No significant differences were observed between the two groups as to their ability to maintain their knowledge of the concepts taught during training or their ability to generalize their skills to the hospital ward immediately following training.

Adolescent↗