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Biomedical subjects

R Dudley

Publications and source records attributed to R Dudley.

At least 19 recordsLinked to original sources

The role of visual cues in directed aerial descent of Cephalotes atratus workers (Hymenoptera: Formicidae).

Animals often depend on properties of reflected light (e.g. color, brightness) to locate resources. We compared reflectance properties of tree trunks with surrounding vegetation, and examined how differences in reflectance profiles of surrogate tree trunks (red, yellow, green, blue, black, gray, dark gray and white sheets) affected the directed aerial descent of worker Cephalotes atratus (L.) ants. Across the visual spectrum, tree trunk reflectance was 2-10 times higher than the surrounding foliage and differed among trees. In two separate experiments, one with colored sheets and one with black, white and gray sheets, nearly half (42% and 47%, respectively) of falling ants directed their descent to a bright white sheet when given a choice of target colors or shades of gray. When colored and gray sheets were presented individually, landing frequencies were lower than expected for all except white sheets. Glide performance was highly variable, but there was a tendency for higher glide indices to be associated with the white sheet relative to the green sheet. We conclude that visually mediated aerial behavior in falling canopy ants is strongly influenced by reflectance properties of the target object, specifically brightness, and correlates with preferred natural targets of tree trunks.

Animals↗

Common variable immune deficiency: respiratory manifestations, pulmonary function and high-resolution CT scan findings.

BACKGROUND: Common variable immune deficiency (CVID) is prone to under-diagnosis and may not reach relevant specialists until late in life. Morbidity is most commonly due to acute-on-chronic respiratory infections leading to respiratory failure. AIM: To investigate respiratory complications, lung function and high-resolution computerized tomography scan (HRCT) findings and mortality in 47 patients with CVID. SETTING: A regional immunology unit (Birmingham Heartlands Hospital). DESIGN: Retrospective observational case-note study following the introduction of shared care between immunology and respiratory medicine. RESULTS: Age at diagnosis ranged from 5 to 72 years, with a median time from development of first symptoms to diagnosis of 4.0 years. There was delay in referral between chest physicians and immunologists, (median referral time between specialities >5 years). Forty-two patients had respiratory complications, due to bronchiectasis (n=32), asthma (n=7), recurrent chest infections (n=9) without concomitant evidence of structural lung damage, and granulomatous lung disease (n=2). Spirometry was abnormal in 10/39 patients (7 obstructive, 3 restrictive). Bronchiectasis was confirmed on chest radiograph (n=9) and HRCT (n=24). Despite the high prevalence of bronchiectasis, few patients had received instruction in physiotherapy and sputum culture results were sparse. DISCUSSION: To reduce the morbidity associated with CVID, there needs to be greater awareness of respiratory complications, particularly amongst physicians caring for such patients. Emphasis has been placed on adequate dosage of immunoglobulin, but early involvement by a respiratory physician is essential to monitor lung function and initiate optimal therapy, to minimize the occurrence and progression of lung damage.

Adult↗

Development of a p53 responsive GFP reporter; identification of live cells with p53 activity.

p53 is among the most intensely studied human proteins because of its vital role as the prototype tumor suppressor. As a result, there are widespread applications for p53 functional analysis in biotechnology as it relates to cancer research. p53 is a potent sequence specific transcription factor, which induces the expression of a number of genes whose products mediate cell cycle arrest and apoptosis. Because the tumor suppressor activity of p53 is dependent on its transcription regulatory function, we have undertaken to develop a p53-responsive green fluorescent protein reporter strategy to enable the identification of live cells containing p53 transcriptional transactivation activity. We demonstrate within the use of GFP fluorescence to monitor both endogenous and plasmid derived p53 biochemical and biological activity. Identifying live cells with p53 activity through GFP fluorescence will have wide application for both in vitro and in vivo studies of the p53 tumor suppressor protein.

Apoptosis↗

Limits to human locomotor performance: phylogenetic origins and comparative perspectives.

Studies of human exercise physiology have been conducted from a largely ahistorical perspective. This approach usefully elucidates proximate limits to locomotor performance, but ignores potential sources of biomechanical and physiological variation that derive from adaptation to ancestral environments. Phylogenetic reconstruction suggests that multiple hominoid lineages, including that leading to Homo sapiens, evolved in African highlands at altitudes of 1000-2000 m. The evolution of human locomotor physiology therefore occurred under conditions of hypobaric hypoxia. In contrast to present-day humans running on treadmills or exercising in otherwise rectilinear trajectories, ancestral patterns of hominid locomotion probably involved intermittent knuckle-walking over variable terrain, occasional bouts of arboreality and an evolving capacity for bipedalism. All such factors represent potential axes of locomotor variation at present unstudied in extant hominoid taxa. As with humans, hummingbirds evolved in mid-montane contexts but pose an extreme contrast with respect to body size, locomotor mode and metabolic capacity. Substantial biomechanical and physiological challenges are associated with flight in hypobaria. Nonetheless, hummingbird lineages demonstrate a progressive invasion of higher elevations and a remarkable tolerance to hypoxia during hovering. Upregulation of aerobic capacity and parallel resistance to hypoxia may represent coupled evolutionary adaptations to flight under high-altitude conditions.

Altitude↗

P53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: effect of inter-laboratory variation.

An association between codon-72 p53 polymorphism and risk of human papillomavirus (HPV)-induced cervical cancer has been found recently, but it has been difficult to replicate. In this study, we assess the impact of inter-laboratory variation in p53 genotyping on the validity of the proposed association. DNA specimens were randomly selected from 54 invasive, squamous cell carcinoma cases, 52 HPV-negative, and 39 HPV-positive controls from a previous case-control study in Brazil. Codon-72 polymorphism was blindly analyzed in three different laboratories. We calculated age- and race-adjusted odds ratios (OR) and 95% confidence intervals (CI) using logistic regression for gauging the association between p53 polymorphism and cervical cancer risk. The proportions of the Arg/Arg, Arg/Pro, and Pro/Pro genotypes varied substantially among laboratories with Kappa coefficients in the 0.49-0.63 range. When disagreement between labs was allowed, the OR for the Arg/Arg genotype, compared to other forms, was as low as 1.5 (95% CI: 0.5-3. 9). In contrast, the OR increased to 8.0 (95% CI: 2.3-28.5) after exclusion of discordant genotypes. Restricting the comparison to HPV-positive controls increased the magnitude of the relation appreciably. After exclusion of all discordant diagnoses, the OR was 21.5 (95% CI: 3.4-137.8), whereas with disagreed genotypes the association was not significant (OR = 2.9, 95% CI: 0.7-11.9). Homozygous codon-72 p53-Arg apparently confers a higher susceptibility to HPV-associated cervical tumorigenesis. However, exposure misclassification consequent to inter-laboratory variation in protocols may affect the ability to detect the association.

Adult↗

Evolutionary origins of human alcoholism in primate frugivory.

Evolutionary origins of alcohol consumption have rarely been considered in studies of ethanol addiction. However, the occurrence of ethanol in ripe and decaying fruit and the substantial heritability of alcoholism in humans suggest an important historical association between primate frugivory and alcohol consumption. Olfactory localization of ripe fruit via volatilized alcohols, the use of ethanol as an appetitive stimulant, and the consumption of fruits with substantial ethanol content potentially characterize all frugivorous primates, including hominoids and the lineage leading to modern humans. Patterns of alcohol use by humans in contemporary environments may thus reflect a maladaptive co-option of ancestral nutritional strategies. Although diverse factors contribute to the expression of alcoholism as a clinical syndrome, historical selection for the consumption of ethanol in the course of frugivory can be viewed as a subtle yet pervasive evolutionary influence on modern humans.

Adaptation, Physiological↗

The evolutionary physiology of animal flight: paleobiological and present perspectives.

Recent geophysical analyses suggest the presence of a late Paleozoic oxygen pulse beginning in the late Devonian and continuing through to the late Carboniferous. During this period, plant terrestrialization and global carbon deposition resulted in a dramatic increase in atmospheric oxygen levels, ultimately yielding concentrations potentially as high as 35% relative to the contemporary value of 21%. Such hyperoxia of the late Paleozoic atmosphere may have physiologically facilitated the initial evolution of insect flight metabolism. Widespread gigantism in late Paleozoic insects and other arthropods is also consistent with enhanced oxygen flux within diffusion-limited tracheal systems. Because total atmospheric pressure increases with increased oxygen partial pressure, concurrently hyperdense conditions would have augmented aerodynamic force production in early forms of flying insects. By the late Permian, evolution of decompositional microbial and fungal communities, together with disequilibrium in rates of carbon deposition, gradually reduced oxygen concentrations to values possibly as low as 15%. The disappearance of giant insects by the end of the Permian is consistent with extinction of these taxa for reasons of asphyxiation on a geological time scale. As with winged insects, the multiple historical origins of vertebrate flight in the late Jurassic and Cretaceous correlate temporally with periods of elevated atmospheric oxygen. Much discussion of flight performance in Archaeopteryx assumes a contemporary atmospheric composition. Elevated oxygen levels in the mid- to late Mesozoic would, however, have facilitated aerodynamic force production and enhanced muscle power output for ancestral birds, as well as for precursors to bats and pterosaurs.

Animals↗

Evidence for phosphorylation-dependent internalization of recombinant human rho1 GABAC receptors.

1. Recombinant wild-type or mutant human rho1 GABA receptors were expressed in human embryonic kidney (HEK) 293 or monkey COS-7 cells and studied using the patch clamp technique. 2. Standard whole-cell recordings with 4 mM Mg-ATP in the patch pipette induced a time-dependent decrease in the GABA-activated current (IGABA) amplitude that was not the result of a decrease in GABA sensitivity. In contrast, IGABA remained stable when recordings were obtained using the perforated patch configuration or with standard whole-cell recording and no Mg-ATP in the patch pipette. 3. The inhibitors of serine/threonine protein kinases KN-62 (20 microM) or staurosporine (20 nM) prevented the time-dependent decrease in the amplitude of IGABA seen in the presence of ATP. Alkaline phosphatase (220 U ml-1), when added to the patch pipette in the absence of ATP, induced a transient potentiation of IGABA. Although the protein kinase C (PKC) activator 4beta-phorbol 12-myristate, 13-acetate (PMA) did not reduce the amplitude of IGABA, inclusion of the catalytic domain of PKC in the recording pipette accelerated the time-dependent decrease in current amplitude. These data suggest that phosphorylation is involved in the regulation of the amplitude of IGABA. 4. Mutation of the three PKC consensus sequences of the rho1 receptor had no significant effect on the decline in IGABA, indicating that direct phosphorylation of these putative sites on the rho1 receptor does not underlie the time-dependent decrease in amplitude. 5. In COS-7 cells transfected with wild-type rho1 receptors, the amplitude of IGABA had completely recovered to the original value when the same cells were repatched after 30-40 min, indicating that the decline in IGABA was a reversible process. 6. The inhibitor of actin filament formation cytochalasin B, when added to the patch pipette in the absence of ATP, induced a time-dependent inactivation suggesting that the actin cytoskeleton may play a role in the regulation of the amplitude. 7. Coincident with the decrease in the amplitude of IGABA, the cell capacitance significantly decreased in the presence of ATP in the patch pipette. This decrease in capacitance was not observed in the absence of Mg-ATP. The decrease in the membrane surface area suggests that receptor internalization could be a potential mechanism for the observed inactivation. 8. At 32 C, compared with 22 C, the rate and magnitude of the decline was increased dramatically. In contrast, at 16 C, no significant change in IGABA was observed over the 20 min recording time. This marked temperature sensitivity is consistent with receptor internalization as a mechanism for the time-dependent decline in IGABA. 9. The specificity of the decrease in IGABA was assessed by coexpressing the voltage-dependent potassium channel Kv1.4 along with the rho1 receptor in HEK293 cells. The amplitude of the potassium current (IKv1.4) exhibited very little decrement in comparison to IGABA suggesting that the putative GABA receptor internalization was not the consequence of a non-specific membrane retrieval.

Adenosine Triphosphate↗

Do neotropical migrant butterflies navigate using a solar compass?

Many tropical butterfly species are well-known for their migratory behaviour. Although these insects can maintain a constant direction throughout the day, the physiological mechanisms of orientation are unknown. It has been argued that tropical migrant butterflies must use a time-compensated sun compass to accomplish their journey, but the crucial experimental manipulations to test this hypothesis have not been conducted. This study reports the results of clock-shift experiments performed with two species of migrating butterflies (Pieridae: Aphrissa statira and Phoebis argante) captured during flight across Lake Gatun, Panama. The observed constant flight bearing of natural controls suggests that these species are capable of performing time-compensated celestial navigation. Our clock-shift experiments suggest that a sun compass is involved. Individuals submitted to a 4 h advance shift took significantly different mean orientations on release compared with control butterflies. The direction of this difference was consistent with the use of a sun compass. The magnitude was approximately half the predicted value if the vanishing bearing of released butterflies was used as the variable to evaluate the effect of time-shifting and approximately three-quarters of that predicted if the estimated heading was the variable used. Mean vanishing bearings of control and experimental butterflies did not correspond to predicted values. This difference can be attributed largely to the combined effects of wind and handling.

Journal Article↗

Atmospheric oxygen, giant Paleozoic insects and the evolution of aerial locomotor performance.

Uniformitarian approaches to the evolution of terrestrial locomotor physiology and animal flight performance have generally presupposed the constancy of atmospheric composition. Recent geophysical data as well as theoretical models suggest that, to the contrary, both oxygen and carbon dioxide concentrations have changed dramatically during defining periods of metazoan evolution. Hyperoxia in the late Paleozoic atmosphere may have physiologically enhanced the initial evolution of tetrapod locomotor energetics; a concurrently hyperdense atmosphere would have augmented aerodynamic force production in early flying insects. Multiple historical origins of vertebrate flight also correlate temporally with geological periods of increased oxygen concentration and atmospheric density. Arthropod as well as amphibian gigantism appear to have been facilitated by a hyperoxic Carboniferous atmosphere and were subsequently eliminated by a late Permian transition to hypoxia. For extant organisms, the transient, chronic and ontogenetic effects of exposure to hyperoxic gas mixtures are poorly understood relative to contemporary understanding of the physiology of oxygen deprivation. Experimentally, the biomechanical and physiological effects of hyperoxia on animal flight performance can be decoupled through the use of gas mixtures that vary in density and oxygen concentration. Such manipulations permit both paleophysiological simulation of ancestral locomotor performance and an analysis of maximal flight capacity in extant forms.

Animals↗

Elastic structures in the vocalization apparatus of the Túngara frog Physalaemus pustulosus (Leptodactylidae).

Histological analysis of the vocal sac and body wall in the leptodactylid frog Physalaemus pustulosus suggests that both muscle and elastic fibers are important in call production. Abdominal musculature as well as abdominal bands of elastin (the lineae masculinae) provide the energy required for exhalation and sound production. Air flowing through the larynx inflates a highly extensible vocal sac lined with muscle and a network of elastic fibers. Inherent elasticity together with muscular activity of the vocal sac likely increase the speed and possibly decrease the energetic costs of lung reinflation following vocalization. The mechanics of call production in P. pustulosus thus involve not only laryngeal activation but also elastic transfer of air between the supralaryngeal vocal sac and abdominal respiratory structures.

Abdominal Muscles↗

Transient hovering performance of hummingbirds under conditions of maximal loading.

Maximal load-lifting capacities of six ruby-throated hummingbirds (Archilochus colubris) were determined under conditions of burst performance. Mechanical power output under maximal loading was then compared with maximal hovering performance in hypodense gas mixtures of normodense air and heliox. The maximal load lifted was similar at air temperatures of 5 and 25 degrees C, and averaged 80% of body mass. The duration of load-lifting was brief, of the order of 1 s, and was probably sustained via phosphagen substrates. Under maximal loading, estimates of muscle mass-specific mechanical power output assuming perfect elastic energy storage averaged 206 W kg-1, compared with 94 W kg-1 during free hovering without loading. Under conditions of limiting performance in hypodense mixtures, maximal mechanical power output was much lower (131 W kg-1, five birds) but was sustained for longer (4 s), demonstrating an inverse relationship between the magnitude and duration of maximum power output. In free hovering flight, stroke amplitude and wingbeat frequency varied in inverse proportion between 5 and 25 degrees C, suggesting thermoregulatory contributions by the flight muscles. Stroke amplitude under conditions of maximal loading reached a geometrical limit at slightly greater than 180 degrees. Previous studies of maximum performance in flying animals have estimated mechanical power output using a simplified actuator disk model without a detailed knowledge of wingbeat frequency and stroke amplitude. The present load-lifting results, together with actuator disc estimates of induced power derived from hypodense heliox experiments, are congruent with previous load-lifting studies of maximum flight performance. For ruby-throated hummingbirds, the inclusion of wingbeat frequency and stroke amplitude in a more detailed aerodynamic model of hovering yields values of mechanical power output 34% higher than previous estimates. More generally, the study of performance limits in flying animals necessitates careful specification of behavioral context as well as quantitative determination of wing and body kinematics.

Animals↗

Oxandrolone in AIDS-wasting myopathy.

OBJECTIVE: To evaluate oxandrolone, an oral anabolic steroid with potent anabolic activity and minimal androgenic effects, for the treatment of AIDS-associated myopathy and wasting. METHODS: In a multicenter, double-blind study, 63 HIV-seropositive men with > 10% loss of body weight were randomized to receive either placebo, 5 mg/day oxandrolone, or 15 mg/day oxandrolone for 16 weeks. Body weight, neuromuscular evaluation, and measures of well-being were repeatedly assessed. RESULTS: Patients who received 15 mg/day oxandrolone showed weight gain throughout the 16-week treatment period. Overall, the 5 mg/day oxandrolone group maintained their weight gain over the 16-week period, whereas the placebo group showed continual weight loss. At week 16, significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo. There were no consistent, dose-related, statistically significant differences from baseline in laboratory values or adverse events. CONCLUSION: Oxandrolone, at a dose of either 5 mg/day or 15 mg/day, in contrast to placebo, had a positive impact on the weight and well-being of HIV-seropositive patients suffering from wasting and weakness. Measurable improvement in muscle strength was not noted at the doses employed in this study. Oxandrolone was well tolerated in all the patients who were enrolled in the study. Based on the results reported here, additional studies using higher doses of oxandrolone seem warranted.

Acquired Immunodeficiency Syndrome↗

Limits to flight energetics of hummingbirds hovering in hypodense and hypoxic gas mixtures.

Hovering hummingbirds offer a model locomotor system for which analyses of both metabolism and flight mechanics are experimentally tractable. Because hummingbirds exhibit the highest mass-specific metabolic rates among vertebrates, maximum performance of hovering flight represents the upper limit of aerobic locomotion in vertebrates. This study evaluates the potential constraints of flight mechanics and oxygen availability on maximum flight performance. Hummingbird flight performance was manipulated non-invasively using air and gas mixtures which influenced metabolism via variable oxygen partial pressure and/or altered flight mechanics via variable air densities. Limits to the locomotor capacity of hovering ruby-throated hummingbirds (Archilochus colubris) were unequivocally indicated by aerodynamic failure in either air/helium or air/heliox mixtures. Air/helium mixtures are hypodense and hypoxic; failure to sustain hovering flight occurred at 63% of the density of sea-level air and at an oxygen concentration of 12%. Air/heliox mixtures are hypodense but normoxic; failure in hovering occurred at 47% of sea-level air density. Thus, hummingbirds demonstrated considerable power reserves in hovering flight as well as hypoxic tolerance. In air/helium mixtures, hovering was limited by oxygen supply and not by flight mechanics. Birds hovering in air/helium mixtures increased their mechanical power output but not their rate of oxygen consumption. By contrast, birds hovering in air/heliox mixtures increased both mechanical performance and metabolic expenditure. Under hypoxia, hovering hummingbirds demonstrated non-negligible, but still limited, capacities for anaerobic metabolism and/or oxygen storage. Depending on the physical context, hummingbird flight performance can therefore be limited by oxygen availability or by flight aerodynamics.

Air↗

Hummingbird hovering performance in hyperoxic heliox: effects of body mass and sex.

Owing to their small size and hovering locomotion, hummingbirds are the most aerobically active vertebrate endotherms. Can hyperoxia enhance the flight performance of this highly oxygen-dependent group? Hovering performance of ruby-throated hummingbirds (Archilochus colubris) was manipulated non-invasively using hyperoxic but hypodense gas mixtures of sea-level air combined with heliox containing 35% O2. This manipulation sheds light on the interplay among metabolic power input, mechanical power output and aerodynamic force production in limiting flight performance. No significant differences in flight mechanics and oxygen consumption were identified between hyperoxic and normoxic conditions. Thus, at least in the present experimental context, hyperoxia did not change the major metabolic and mechanical parameters; O2 diffusive capacities of the respiratory system were probably not limiting to a significant extent. Compared with hummingbirds in our previous studies, the present experimental birds were heavier, had resultant shorter hover-feeding durations and experienced aerodynamic failure at higher air densities. Because hummingbirds have relatively stable wingbeat frequencies, modulation of power output was attained primarily through variation in stroke amplitude up to near 180 degrees. This result indicates that maximum hovering performance was constrained geometrically and that heavier birds with greater fat loads had less margin for enhancement of power production. Sexual dimorphism in flight adaptation also played a role, with males showing more limited hovering capacities, presumably as a trade-off for increased maneuverability.

Adipose Tissue↗

Animal flight mechanics in physically variable gas mixtures

Empirical studies of animal flight performance have generally been implemented within the contemporary atmosphere. Experimental alteration of the physical composition of gas mixtures, however, permits construction of novel flight media and the non-invasive manipulation of flight biomechanics. For example, replacement of atmospheric nitrogen with various noble gases results in a tenfold variation in air density at a constant oxygen concentration. Such variation in air density correspondingly elicits extraordinary biomechanical effort from flying animals; hummingbirds and euglossine orchid bees hovering in such low-density but normoxic mixtures have demonstrated exceptionally high values for the mechanical power output of aerobic flight muscle. As with mechanical power, lift coefficients during hovering increase at low air densities in spite of a concomitant decline in the Reynolds number of the wings. The physical effects of variable gas density may also be manifest in morphological and physiological adaptations of animals to flight across altitudinal gradients. Global variation in atmospheric composition during the late Paleozoic may also have influenced the initial evolution and subsequent diversification of ancestral pterygotes. For the present-day experimenter, the use of physically variable flight media represents a versatile opportunity to explore the range of kinematic and aerodynamic modulation available to flying animals.

Journal Article↗