Biomedical subjects

S P Roberts

Publications and source records attributed to S P Roberts.

At least 19 recordsLinked to original sources

PubMed2005

Environmental hypoxia influences hemoglobin subunit composition in the branchiopod crustacean Triops longicaudatus.

Hemoglobin (Hb) is a highly conserved protein that provides a vital link between environmental oxygen and its use and/or storage within an organism. While ubiquitous among vertebrates, Hb occurs frequently in invertebrate phyla as well. Many arthropod species use the copper-binding pigment hemocyanin, but unique in this phylum are the branchiopod crustaceans, which express Hb. Branchiopod Hb concentration and structure are exquisitely sensitive to environmental oxygen availability. Hemoglobin concentration and oxygen-binding affinity increase with decreasing oxygen tension in Daphnia, Artemia and Triops. The change in binding affinity is attributed to differential Hb subunit expression in Daphnia and Artemia but remains unclear for Triops. This is the first study to demonstrate developmental plasticity of Hb subunit expression in a notostracan, Triops longicaudatus, reared under conditions of varying oxygen availability. In response to variable oxygen environments, T. longicaudatus differentially express four primary Hb subunits ranging between 30 and 34 kDa, with normoxic-reared animals expressing primarily the heavier subunits, and hypoxic-reared animals expressing increased proportions of the lower molecular mass subunits. Moreover, differential Hb subunit expression is induced upon transfer of normoxic-reared adults to a hypoxic environment, such that the distribution of Hb subunits in the transferred adults becomes similar to that of hypoxic-reared animals. Two-dimensional gel electrophoresis and follow-up analyses revealed several isoforms of Hb subunits that may represent differential gene expression and/or post-translational modification. Unlike Daphnia and Artemia, the Hb hypoxic response in Triops is not reversible in that there was no significant decrease in Hb concentration or change in Hb subunit expression pattern when hypoxic-reared adults were transferred to a normoxic environment.

Amino Acid Sequence↗

PubMed2001

Nonpeptide cholecystokinin-2 receptor agonists.

In the course of structural explorations around a series of potent CCK2 receptor antagonists, it was noted that simple N-methylation of the indolic N-H in the parent molecule gave rise to behavior in vivo that was consistent with the compound acting as an agonist. Exploration in vitro confirmed this property, and it was shown that the agonist action could be blocked by the reference CCK2 receptor antagonist, L-365,260. Further examples of this type of modification were explored, and a common theme with regard to agonist behavior was uncovered. Some molecular modeling is also presented in an attempt to throw light on the nature of the ligand receptor interactions that may be giving rise to the differing properties of these, apparently, structurally similar molecules.

Adamantane↗

PubMed2000

Flight respiration and energetics.

We use a comparative approach to examine some of the physiological traits that make flight possible. Comparisons of related fliers and runners suggest that fliers generally have higher aerobic metabolic capacities than runners but that the difference is highly dependent on the taxa studied. The high metabolic rates of fliers relative to runners, especially in insects, are correlated with high locomotory muscle cycle frequencies and low efficiencies of conversion of metabolic power to mechanical power. We examine some factors that produce variation in flight respiration and energetics. Air temperature strongly affects the flight metabolic rate of some insects and birds. Flight speed interacts with flier mass, so that small fliers tend to exhibit a J-shaped power curve and larger fliers a U-shaped power curve. As body size increases, mass-specific aerobic flight metabolism decreases in most studies, but mass-specific power output is constant or increases, leading to an increase in efficiency with size. Intraspecific studies have revealed specific genetically based effects on flight metabolism and power output and multiple ecological correlates of flight capabilities.

Animals↗

PubMed1998

Mechanisms of thermal balance in flying Centris pallida (Hymenoptera: Anthophoridae).

Thermoregulation of the thorax is critical for bees and other endothermic insects to achieve high rates of flight muscle power production. However, the mechanisms allowing insects to regulate thorax temperatures during flight are not well understood. To test whether variations in metabolic heat production, evaporation or heat transfer from the thorax to the abdomen contribute to the maintenance of stable body temperatures during flight in the bee Centris pallida, we measured CO2 production, water vapor loss, wingbeat frequency and body segment temperatures during flight at varying air temperatures (Ta). While hovering in the field and while flying in the respirometer, C. pallida males maintain extremely stable, elevated thorax temperatures (45+/-2 degrees C; mean +/- S.E.M.). Measurements of head, thorax and abdomen temperatures as a function of Ta during hovering flight in the field indicated that C. pallida males were not actively increasing heat transfer from the thorax to the head or abdomen at high Ta values. As Ta increased from 26 to 35 degrees C, increases in evaporative water loss were relatively small compared with the decrease in carbon dioxide emission. As Ta values increased from 26 to 35 degrees C, the factorial decreases in metabolic heat production and the elevation of thorax temperature above Ta were closely matched (35 %), suggesting that variation in metabolic heat production is the major mechanism of thermoregulation in flying C. pallida. The thermal effects on rates of water loss and metabolic water production resulted in a strong positive water balance at cooler Ta values, but a strong negative water balance at Ta values above 31 degrees C. During the first minute of flight in the respirometry chamber, wingbeat frequency was independent of Ta. However, by the fourth minute, there was a significant negative relationship between Ta and wingbeat frequency, which was similar to the thermal relationship observed for wingbeat frequency in the field. These data suggest that, either through homeostatic regulation or resulting secondarily from thermal effects on flight motor properties, variation in metabolic heat production may occur via altered wingbeat kinematics.

Animals↗

PubMed1996

Energy metabolism, enzymatic flux capacities, and metabolic flux rates in flying honeybees.

Honeybees rely primarily on the oxidation of hexose sugars to provide the energy required for flight. Measurement of VCO2 (equal to VO2, because VCO2/VO2 = 1.0 during carbohydrate oxidation) during flight allowed estimation of steady-state flux rates through pathways of flight muscle energy metabolism. Comparison of Vmax values for flight muscle hexokinase, phosphofructokinase, citrate synthase, and cytochrome c oxidase with rates of carbon and O2 flux during flight reveal that these enzymes operate closer to Vmax in the flight muscles of flying honeybees than in other muscles previously studied. Possible mechanistic and evolutionary implications of these findings are discussed.

Animals↗

PubMed1996

Achievement of thermal stability by varying metabolic heat production in flying honeybees.

Thermoregulation of the thorax allows endothermic insects to achieve power outputs during flight that are among the highest in the animal kingdom. Flying endothermic insects, including the honeybee Apis mellifera, are believed to thermoregulate almost exclusively by varying heat loss. Here it is shown that a rise in air temperature from 20 degrees to 40 degrees C causes large decreases in metabolic heat production and wing-beat frequency in honeybees during hovering, agitated, or loaded flight. Thus, variation in heat production may be the primary mechanism for achieving thermal stability in flying honeybees, and this mechanism may occur commonly in endothermic insects.

Animals↗

PubMed1996

Analysis of variation in L-365,260 competition curves in radioligand binding assays.

1. For several years, we have used the cholecystokinin (CCK)B/gastrin receptor selective antagonist, L-365,260, as a reference compound in a variety of studies in CCKB/gastrin receptor radioligand binding assays. Here, we have analysed the competition curve data sets obtained between L-365,260 and [125I]-BH-CCK8S in guinea-pig gastric gland and mouse and rat cerebral cortex preparations. 2. Competition curves obtained for L-365,260 in the mouse cortex assay were not different from rectangular hyperbolae (slope = 1.01 +/- 0.02) implying the presence of a single population of binding sites (pKI = 8.41 +/- 0.01; data from 47 experiments, slope constrained to unity). However, in the rat cortex and guinea-pig gastric gland assays, the mean slope of the competition curves was significantly less than one and the mean apparent pKI significantly lower than that obtained in the mouse cortex (slope = 0.85 +/- 0.03, 0.90 +/- 0.03; apparent pKI = 7.98 +/- 0.05, 8.07 +/- 0.05; 48 and 45 experiments, in rat and guinea-pig, respectively). The distribution of the individual pKI and slope estimates of the competition curves in these two assays was consistent with expectations for the variable expression (in terms of absolute number and proportion) of two binding sites. The two sites were characterized by pKI values for L-365,260 of 8.50 +/- 0.04 and 8.48 +/- 0.04 for the high affinity site and 7.32 +/- 0.04 and 7.22 +/- 0.06 for the low affinity site in guinea-pig and rat, respectively. 3. The affinity estimates for L-365,260, although obtained on different tissues, are consistent with data obtained from the analysis of L-365,260 antagonism of pentagastrin-stimulated responses in mouse and rat stomach (acid secretion) and guinea-pig gastric muscle (isotonic contraction) assays. To this extent, these data suggest the existence of two CCKB/gastrin receptor subtypes.

Animals↗

PubMed1996

Analysis of the variation in the action of L-365,260 at CCKB/gastrin receptors in rat, guinea-pig and mouse isolated gastric tissue assays.

1. Since L-365,260 was first described as a selective antagonist at cholecystokinin (CCK)B/gastrin receptors, we have used it periodically as a reference compound in isolated tissue assays of guinea-pig gastric muscle and lumen-perfused stomachs from mouse and immature rat. L-365,260 behaved as a surmountable antagonist and produced parallel rightward shifts of pentagastrin concentration-effect curves' in each of the replicate experiments. The experiments were performed by several different experimenters in the same laboratories over a five year period. 2. In the isolated, lumen-perfused, immature rat stomach assay, L-365,260 behaved as a simple competitive antagonist (Schild plot slope = 1.00 +/- 0.10, pKB = 7.54 +/- 0.03 from a global analysis of the data) acting at a homogeneous population of receptors in five separate, highly-reproducible, experiments. In contrast, the replicate data sets obtained from the interaction in the isolated, lumen-perfused mouse stomach and guinea-pig gastric muscle assays, over the same period, were not consistent with the presence of a single receptor population. The guinea-pig gastric muscle data were relatively reproducible between experiments but some individual Schild plot slopes and the slope estimated from a global analysis of all the data were significantly less than unity (slope = 0.80 +/- 0.07, pA2 = 8.56 +/- 0.05 from the global analysis). The data obtained in the mouse stomach were significantly more variable than that obtained in the same assay, during the same period, from the interaction between histamine and the H2-receptor antagonist, famotidine. The individual Schild plot slopes ranged from being very flat (0.20) to being not significantly different from unity (1.23) and the pA2 values ranged from 7.68 to 8.70. 3. Overall, the data could be accounted for by assuming the variable expression of two receptor subtypes across the assays. The rat stomach appeared to express a single receptor characterized by a low affinity constant for L-365,260 (pKB approximately 7.5). The guinea-pig gastric muscle and mouse stomach data could be explained by the presence of this receptor and a second one characterized by a high affinity constant for L-365,260 (pKB approximately 8.6). The activity of the two proposed receptor subtypes was consistent between experiments in the guinea-pig and the high affinity receptor appeared to be predominant. In contrast, the mouse stomach data could only be simulated by assuming that the proportion and absolute number of each subtype varied significantly between the replicate experiments. 4. The L-365,260 affinity estimates at the inferred receptor subtypes were indistinguishable from those obtained in a corresponding analysis of the behaviour of L-365,260 in CCKB/gastrin receptor radioligand binding experiments in guinea-pig gastric gland and mouse and rat cerebral cortex preparations.

Animals↗

PubMed1996

Pharmacological analysis of the CCKB/gastrin receptors mediating pentagastrin-stimulated gastric acid secretion in the isolated stomach of the immature rat.

1. The CCKB/gastrin receptors mediating pentagastrin stimulation of gastric acid secretion by histamine release and by direct stimulation of oxyntic cells have been characterized in the immature rat isolated stomach assay. This was achieved by estimating antagonist affinity values for competitive antagonists from three distinct chemical classes (L-365,260, PD134,308 and JB93190) in the absence and presence of a high concentration of the histamine H2-receptor antagonist, famotidine (30 microM). 2. Pentagastrin produced concentration-dependent stimulation of gastric acid secretion in the absence and presence of famotidine. Famotidine depressed the maximum secretory response to pentagastrin although the degree of depression varied between experimental replicates (25-60%). This variation was attributed to the histamine-release mediated component of acid secretion, as judged by the consistency of the maximum responses obtained in the presence, but not absence, of famotidine. 3. All three CCKB/gastrin receptor antagonists behaved as surmountable antagonists in the absence and presence of famotidine. JB93190 (pKB approximately 9.1, approximately 8.9, in the absence and presence of famotidine, respectively) was approximately 30 fold more potent than either L-365,260 (pKB approximately 7.4, approximately 7.1) or PD134,308 (pKB approximately 7.6, approximately 7.4). 4. It was assumed that the famotidine treatment converted pentagastrin-stimulated acid secretion from a combination of an indirect action due to the release of histamine and a direct action on the oxyntic cell to solely a direct action on the oxyntic cell. A simple mathematical model of this two-receptor system was developed. The direct and indirect components were assumed to sum to produce the total response to pentagastrin obtained in the absence of famotidine. It was found that this model could account quantitatively for the behaviour of the three antagonists without invoking a difference in antagonist affinity for the CCKB/gastrin receptors mediating the direct and indirect actions of pentagastrin. However, a conclusion of receptor homogeneity has to be qualified because the model was also used to generate simulations which indicated that the analysis could only detect antagonist affinity differences of greater than one log-unit between enterochromaffin-like (ECL) and oxyntic cell CCKB/gastrin receptor populations.

Animals↗

PubMed1994

Solid state NMR imaging of irreducible water in reservoir cores for spatially resolved pore surface relaxation estimation.

The use of solid state NMR imaging in reservoir core applications has long been proposed. This paper describes the use of a simple, robust technique in the first such application. One- and two-dimensional images of the irreducible brine in a sandstone and carbonate reservoir core are demonstrated. The applicability of solid state NMR imaging to pore surface relaxation estimation is discussed.

Carbonates↗

PubMed1993

Extending a pipecuronium neuromuscular block. Increments of atracurium or vecuronium as an alternative to pipecuronium.

Ten patients received increasing doses of pipecuronium at induction of anaesthesia. A dose response relationship was then constructed from which ED90 and ED95 values were measured as 43.4 micrograms.kg-1 and 50.5 micrograms.kg-1 respectively. A further 30 patients received pipecuronium in a dose sufficient to produce greater than 90% neuromuscular block. When the first contraction of the train-of-four had returned to 10% of control, a small increment of atracurium (1.1 mg), vercuronium (0.25 mg) or pipecuronium (0.21 mg) was administered, and this was repeated subsequently using the same criterion of recovery on each occasion. The duration and intensity of the block with pipecuronium increments remained constant. The duration of the block following atracurium or vecuronium was progressively less with subsequent increments until steady state was reached. The final mean durations at steady state were pipecuronium 7.37 min, atracurium 6.99 min, and vecuronium 5.15 min.

Adolescent↗

PubMed1993

The onset of alcuronium and tubocurarine: alone and in combination.

The rates of onset of neuromuscular blockade have been measured following 0.25 mg.kg-1 alcuronium (ED95), 0.51 mg.kg-1 tubocurarine (ED95), a combination of 50% of the ED95 of each and a combination of 33% of the ED95 of each. Train-of-four stimulation of the ulnar nerve was used with recording of the amplitude of the evoked compound electromyogram from the thenar prominence. The rate of increase in blockade in patients receiving the 50% combination was significantly greater than for either agent given alone, or than for the 33% combination. The mean time to 75% block of the first contraction of the train (T1) with the 50% mixture was 90 s, significantly faster than alcuronium alone (132 s), tubocurarine alone (174 s) or the 33% mixture (127 s). These latter three groups did not differ significantly. In conclusion, the rate of onset of the 50% combination resulted in a more rapid onset of neuromuscular blockade, whereas the rate of onset of the 33% combination was no different to that of either drug alone. This small degree of acceleration with agents which are known to be markedly synergistic makes it unlikely that this technique will prove to be of clinical importance.

Adult↗

PubMed1993

The use of midazolam and flumazenil for invasive radiographic procedures.

This study has examined the use of flumazenil to improve recovery following sedation with midazolam in elderly patients undergoing invasive radiological procedures. Forty patients received either flumazenil or placebo in a randomized double-blind fashion following midazolam sedation. Nalbuphine 10-15 mg was given for premedication. All but one of the patients in the flumazenil group were fully awake immediately following the reversal agents compared to only one in the placebo group (P = 0.016). This statistically significant difference remained after 20 minutes (P = 0.029). There were no adverse effects on heart rate, blood pressure, forced expiratory volume in one second, vital capacity or oxygen saturation. The majority of patients (78% overall) could not recall their procedure. All patients said that they would be willing to undergo a similar technique in the future.

Aged↗

PubMed1992

SK&F 104078, a post-junctionally selective alpha 2-adrenoceptor antagonist in the human saphenous vein in vitro.

The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1H,2,3,4,- tetrahydro-3-benzazapine) at pre- and post-junctional alpha 2-adrenoceptors in the human isolated saphenous vein. Noradrenaline (0.001-100 mumol/l) produced concentration-dependent contractions of the human saphenous vein which were competitively antagonised by the alpha 1-adrenoceptor antagonist prazosin (0.01-1.0 mumol/l) and the alpha 2-adrenoceptor antagonist, rauwolscine (0.01-1.0 mumol/l), indicating the presence of both post-junctional alpha 1- and alpha 2-adrenoceptors in this preparation. The selective alpha 2-adrenoceptor agonist, UK-14,304 (0.01-100 mumol/l) also produced concentration-dependent contractions of the human saphenous vein which were antagonised by both rauwolscine (0.1 mumol/l) and prazosin (0.1 mumol/l). In the presence of angiotensin II (0.05 mumol/l), which itself produced a transient contraction, rauwolscine (0.1 mumol/l) produced a rightward shift of the UK-14,304 concentration-response curve while prazosin (0.1 mumol/l) had no effect. SK&F 104078 (10.0 mumol/l) under these conditions also produced a rightward shift of the concentration-response curve to UK-14,304, but was at least 100-fold less potent than rauwolscine. At pre-junctional alpha 2-adrenoceptors, exogenous noradrenaline (0.01 and 0.1 mumol/l) induced a concentration-dependent inhibition of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein in vitro, which was antagonised by rauwolscine (0.1 mumol/l) and tolazoline (10.0 mumol/l) but not by SK&F 104078 (10.0 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1992

Central retinal vein occlusion in a middle-aged adult with HIV infection.

Recently central retinal vein occlusion (CRVO) has been described as a possible AIDS-related phenomenon. We have seen another case of CRVO in a middle-aged male with HIV infection. Extensive laboratory testing failed to reveal any other systemic abnormality which might be contributory. The potential role of HIV infection in the pathogenesis of CRVO is discussed.

Fluorescein Angiography↗

PubMed1992

Traumatic avulsion of the optic nerve.

Avulsion of the optic nerve is an infrequent traumatic event which results in a permanent and usually devastating loss of vision. We present two cases which highlight the salient features of partial and complete optic nerve avulsion. The clinical findings, including the results of B-scan ultrasonography, fluorescein angiography, and computed tomography (CT) are discussed. In addition, the past two decades of literature pertaining to optic nerve avulsion are reviewed and summarized.

Adult↗

PubMed1992

Malignant hyperpyrexia: a rare cause of postoperative death.

A middle aged man developed very high fever, status epilepticus, and terminal acute renal failure with myoglobinuria after surgery. A post mortem examination showed widespread muscle necrosis with hypercontraction bands. Muscle enzyme studies and electron microscopic examination disclosed central core disease, a condition closely related to malignant hyperpyrexia. This condition is a genetically inherited disorder which can be triggered by certain volatile anaesthetic agents or Suxamethonium. In this patient the condition may have been triggered by either the Isoflurane or the postoperative status epilepticus.

Humans↗

PubMed1992

Visual disorders of higher cortical function.

Following stroke or other causes of brain damage, patients may demonstrate visual disorders of higher cortical function. These defects involve visual attention, oculomotor skills, visuospatial orientation and object recognition. It is important for optometrists to understand these conditions and consider their presence in individuals with persistent visual complaints despite a normal exam, or in patients who fail to respond to magnification in low vision rehabilitation. The diagnosis and management of these higher order visual disturbances are discussed.

Agnosia↗