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Ultrastructure of potato tubers formed in microgravity under controlled environmental conditions.

Previous spaceflight reports attribute changes in plant ultrastructure to microgravity, but it was thought that the changes might result from growth in uncontrolled environments during spaceflight. To test this possibility, potato explants were examined (a leaf, axillary bud, and small stem segment) grown in the ASTROCULTURETM plant growth unit, which provided a controlled environment. During the 16 d flight of space shuttle Columbia (STS-73), the axillary bud of each explant developed into a mature tuber. Upon return to Earth, tuber slices were examined by transmission electron microscopy. Results showed that the cell ultrastructure of flight-grown tubers could not be distinguished from that of tuber cells grown in the same growth unit on the ground. No differences were observed in cellular features such as protein crystals, plastids with starch grains, mitochondria, rough ER, or plasmodesmata. Cell wall structure, including underlying microtubules, was typical of ground-grown plants. Because cell walls of tubers formed in space were not required to provide support against the force due to gravity, it was hypothesized that these walls might exhibit differences in wall components as compared with walls formed in Earth-grown tubers. Wall components were immunolocalized at the TEM level using monoclonal antibodies JIM 5 and JIM 7, which recognize epitopes of pectins, molecules thought to contribute to wall rigidity and cell adhesion. No difference in presence, abundance or distribution of these pectin epitopes was seen between space- and Earth-grown tubers. This evidence indicates that for the parameters studied, microgravity does not affect the cellular structure of plants grown under controlled environmental conditions.

Environment↗

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance.

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

Adult↗

Development of a hydraulic model of the human systemic circulation.

Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

Aorta↗

Feedback control of mean aortic pressure in a dynamic model of the cardiovascular system.

Orbital measurements of the cardiac function of Space Shuttle crew members have shown an initial increase in cardiac stroke volume upon entry into weightlessness, followed by a gradual reduction in stroke volume to a level approximately 15% less than preflight values. In an effort to explain this response, it was hypothesized that gravity plays a role in cardiac filling. A mock circulatory system was designed to investigate this effect. Preliminary studies carried out with this system on the NASA KC-135 aircraft, which provides brief periods of weightlessness, showed a strong correlation between cardiac filling, stroke volume, and the presence or absence of gravity. The need for extended periods of high quality zero gravity was identified to verify this observation. To accomplish this, the aircraft version of the experiment was reduced in size and fully automated for eventual integration into a Get Away Special canister to conduct an orbital version of the experiment. This article describes the automated system, as well as the development and implementation of a control algorithm for the servoregulation of the mean aortic pressure in the orbital experiment. Three nonlinearities that influence the ability of the apparatus to regulate to a mean aortic pressure of 95 mm Hg were identified and minimized. In preparation for a Space Shuttle flight, the successful function of the servoregulatory scheme was demonstrated during ground tests and additional test flights aboard the KC-135. The control algorithm was successful in carrying out the experimental protocol, including regulation of mean aortic pressure. The algorithm could also be used for the automated operation of long-term tests of circulatory support systems, which may require a scheduled cycling of the pumping conditions on a daily basis.

Algorithms↗

Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness.

This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induce BV expansion: PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, while EV decreases may result from increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation which suppresses erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.

Adaptation, Physiological↗

Comparison of sympathetic nerve responses to neck and forearm isometric exercise.

PURPOSE: Although the autonomic and cardiovascular responses to arm and leg exercise have been studied, the sympathetic adjustments to exercise of the neck have not. The purpose of the present study was twofold: 1) to determine sympathetic and cardiovascular responses to isometric contractions of the neck extensors and 2) to compare sympathetic and cardiovascular responses to isometric exercise of the neck and forearm. METHODS: Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate were measured in nine healthy subjects while performing isometric neck extension (INE) and isometric handgrip (IHG) in the prone position. After a 3-min baseline period, subjects performed three intensities of INE for 2.5 min each: 1) unloaded (supporting head alone), 2) 10% maximal voluntary contraction (MVC), and 3) 30% MVC, then subjects performed two intensities (10% and 30% MVC) of IHG for 2.5 min. RESULTS: Supporting the head by itself did not significantly change any of the variables. During [NE, MAP significantly increased by 10 +/- 2 and 31 +/- 4 mm Hg and MSNA increased by 67 +/- 46 and 168 +/- 36 units/30 s for 10% and 30% MVC, respectively. IHG and INE evoked similar responses at 10% MVC, but IHG elicited higher peak MAP and MSNA at 30% MVC (37 +/- 7 mm Hg (P < 0.05) and 300 +/- 48 units/30 s (P < 0.01) for IHG, respectively). CONCLUSIONS: The data indicate that INE can elicit marked increases in MSNA and cardiovascular responses but that it evokes lower peak responses as compared to IHG. We speculate that possible differences in muscle fiber type composition, muscle mass, and/or muscle architecture of the neck and forearm are responsible for these differences in peak responses.

Adult↗

New imaging technology: measurement of myocardial perfusion by contrast echocardiography.

Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.

Contrast Media↗

Sleep deprivation influences some but not all processes of supervisory attention.

Does one night of sleep deprivation alter processes of supervisory attention in general or only a specific subset of such processes? Twenty college-aged volunteers, half female, performed a choice reaction time task. A cue indicated that compatible (e.g., right button, right-pointing arrow) or incompatible (e.g., left button, right-pointing arrow) responses were to be given to a stimulus that followed 50 or 500 ms later. The paradigm assessed response inhibition, task-shifting skill, and task strategy-processes inherent in supervisory attention. Performance, along with heart rate, was assessed for 12 hr following normal sleep or a night of complete sleep deprivation. Sleep deprivation altered neither preparation for task shifting nor response inhibition. The ability to use preparatory bias to speed performance did decrease with sleep deprivation. Sleep deprivation appears to selectively affect this supervisory attention process, which is perceived as an active effort to cope with a challenging task.

Adult↗

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy.

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

Adult↗

Directional abnormalities of vestibular and optokinetic responses in cerebellar disease.

Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three-axis magnetic search-coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross-coupling were found during (1) high-frequency, high-acceleration head thrusts; (2) constant-velocity chair rotations with the head fixed; (3) constant-velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross-coupling during horizontal head thrusts consisted of an inappropriate upward eye-velocity component. In some patients, sustained constant-velocity yaw-axis chair rotations produced a mixed horizontal-torsional nystagmus and/or an increase in the baseline vertical slow-phase velocity. Following horizontal head shaking, some patients showed an increase in the slow-phase velocity of their downbeat nystagmus. These various forms of cross-coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross-coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross-coupling during constant-velocity rotations and following head shaking may result from a misorientation of the angular eye-velocity vector in the velocity-storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal-lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.

Adult↗

Bioelectrical impedance analysis. What does it measure?

Bioelectrical impedance analysis (BIA) has been proposed for measuring fat-free mass, total body water, percent fat, body cell mass, intracellular water, and extracellular water: a veritable laboratory in a box. Although it is unlikely that BIA is quite this versatile, correlations have been demonstrated between BIA and all of these body compartments. At the same time, it is known that all of the compartments are correlated among themselves. Because of this, it is difficult to determine whether BIA is specific for any or all of these compartments. To investigate this question, we induced acute changes in total body water and its compartments over a 3-h period. Using this approach, we demonstrated that multifrequency BIA, using the Cole-Cole model to calculate the zero frequency and infinite frequency resistance, measures extracellular and intracellular water.

Adipose Tissue↗

The human respiratory gate.

Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

Autonomic Nervous System↗

A phase response curve to single bright light pulses in human subjects.

The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

Adult↗

Multiple Epstein-Barr virus infections in healthy individuals.

We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals. Infections with up to five different EBV genotypes were found in two of nine individuals studied. These results support the hypothesis that multiple EBV infections of healthy individuals are common. The implications for the development of an EBV vaccine are discussed.

Amino Acid Sequence↗

Error, stress, and teamwork in medicine and aviation: cross sectional surveys.

OBJECTIVES: To survey operating theatre and intensive care unit staff about attitudes concerning error, stress, and teamwork and to compare these attitudes with those of airline cockpit crew. DESIGN: : Cross sectional surveys. SETTING: : Urban teaching and non-teaching hospitals in the United States, Israel, Germany, Switzerland, and Italy. Major airlines around the world. PARTICIPANTS: : 1033 doctors, nurses, fellows, and residents working in operating theatres and intensive care units and over 30 000 cockpit crew members (captains, first officers, and second officers). MAIN OUTCOME MEASURES: : Perceptions of error, stress, and teamwork. RESULTS: : Pilots were least likely to deny the effects of fatigue on performance (26% v 70% of consultant surgeons and 47% of consultant anaesthetists). Most pilots (97%) and intensive care staff (94%) rejected steep hierarchies (in which senior team members are not open to input from junior members), but only 55% of consultant surgeons rejected such hierarchies. High levels of teamwork with consultant surgeons were reported by 73% of surgical residents, 64% of consultant surgeons, 39% of anaesthesia consultants, 28% of surgical nurses, 25% of anaesthetic nurses, and 10% of anaesthetic residents. Only a third of staff reported that errors are handled appropriately at their hospital. A third of intensive care staff did not acknowledge that they make errors. Over half of intensive care staff reported that they find it difficult to discuss mistakes. CONCLUSIONS: Medical staff reported that error is important but difficult to discuss and not handled well in their hospital. Barriers to discussing error are more important since medical staff seem to deny the effect of stress and fatigue on performance. Further problems include differing perceptions of teamwork among team members and reluctance of senior theatre staff to accept input from junior members.

Attitude↗

Common endocrine control of body weight, reproduction, and bone mass.

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

Body Weight↗