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Biomedical subjects

S J Wood

Publications and source records attributed to S J Wood.

At least 19 recordsLinked to original sources
PubMed2001

Orthostatic intolerance and motion sickness after parabolic flight.

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Adult↗
PubMed2000

Parkinson's disease-associated alpha-synuclein is more fibrillogenic than beta- and gamma-synuclein and cannot cross-seed its homologs.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies. Recently, two point mutations in alpha-synuclein were found to be associated with familial PD, but as of yet no mutations have been described in the homologous genes beta- and gamma-synuclein. alpha-Synuclein forms the major fibrillar component of Lewy bodies, but these do not stain for beta- or gamma-synuclein. This result is very surprising, given the extent of sequence conservation and the high similarity in expression and subcellular localization, in particular between alpha- and beta-synuclein. Here we compare in vitro fibrillogenesis of all three purified synucleins. We show that fresh solutions of alpha-, beta-, and gamma- synuclein show the same natively unfolded structure. While over time alpha-synuclein forms the previously described fibrils, no fibrils could be detected for beta- and gamma-synuclein under the same conditions. Most importantly, beta- and gamma-synuclein could not be cross-seeded with alpha-synuclein fibrils. However, under conditions that drastically accelerate aggregation, gamma-synuclein can form fibrils with a lag phase roughly three times longer than alpha-synuclein. These results indicate that beta- and gamma-synuclein are intrinsically less fibrillogenic than alpha-synuclein and cannot form mixed fibrils with alpha-synuclein, which may explain why they do not appear in the pathological hallmarks of PD, although they are closely related to alpha-synuclein and are also abundant in brain.

Amino Acid Sequence↗
PubMed2000

Transient cardio-respiratory responses to visually induced tilt illusions.

Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally. Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated.

Adult↗
PubMed2000

An optimized method for estimating intracranial volume from magnetic resonance images.

The accuracy and efficiency of protocols to measure intracranial volume (ICV) from volumetric magnetic resonance imaging (MRI) studies has not been formally analyzed. The ICV of 30 control participants was obtained by tracing every slice of a MRI data set on which the cranial cavity appeared, and compared with estimated ICVs calculated by progressively selecting one of every x slices (i.e., "1-in-x") as a sampling strategy. The reliability and precision of each sampling strategy was then determined. There was virtually no reduction in reliability at the 1-in-10 sampling strategy, with a reliability exceeding 0.999. ICV can be confidently traced using a 1-in-10 sampling strategy, which should result in significant time savings.

Adolescent↗
PubMed2000

Reciprocal modulation of glutamate and GABA release may underlie the anticonvulsant effect of phenytoin.

Although conventional wisdom suggests that the effectiveness of phenytoin as an anticonvulsant is due to blockade of Na+-channels this is unlikely to be it's sole mechanism of action. In the present paper we examined the effects of phenytoin on evoked and spontaneous transmission at excitatory (glutamate) and inhibitory (GABA) synapses, in the rat entorhinal cortex in vitro. Evoked excitatory postsynaptic potentials at glutamate synapses exhibited frequency-dependent enhancement, and phenytoin reduced this enhancement without altering responses evoked at low frequency. In whole-cell patch-clamp recordings the frequency of excitatory postsynaptic currents resulting from the spontaneous release of glutamate was reduced by phenytoin, with no change in amplitude, rise time or decay time. Similar effects were seen on miniature excitatory postsynaptic currents, recorded in the presence of tetrodotoxin. Evoked inhibitory postsynaptic potentials at GABA synapses displayed a frequency-dependent decrease in amplitude. Phenytoin caused a reduction in this decrement without affecting the responses evoked at low frequency. The frequency of spontaneous GABA-mediated inhibitory postsynaptic currents, recorded in whole-cell patch mode, was increased by phenytoin, and this was accompanied by the appearance of much larger amplitude events. The effect of phenytoin on the frequency of inhibitory postsynaptic currents persisted in the presence of tetrodotoxin, but the change in amplitude distribution largely disappeared. These results demonstrate for the first time that phenytoin can cause a simultaneous reduction in synaptic excitation and an increase in inhibition in cortical networks. The shift in balance in favour of inhibition could be a major factor in the anticonvulsant action of phenytoin.

2-Amino-5-phosphonovalerate↗
PubMed2000

Evidence for progression of brain structural abnormalities in schizophrenia: beyond the neurodevelopmental model.

OBJECTIVE: Clinical, neuroimaging, neuropathological and neuropsychological evidence suggests that, in schizophrenia, there is structural and functional disturbance of the hippocampus. The purpose of this paper is to present published findings concerning the nature, timing and course of these putative disturbances of hippocampal function and the pathophysiological mechanisms involved, and to explore whether schizophrenia is a disorder of neurodevelopment, neurodegeneration or a combination of both processes. METHOD: The available cross-sectional and longitudinal evidence for hippocampal involvement in schizophrenia is reviewed and a model of hippocampal involvement in this disorder, which derives from our own cross-sectional and longitudinal hippocampal imaging data, is described. RESULTS: We propose a three-hit model in which an early neurodevelopmental lesion renders the hippocampus vulnerable to further insult later in life during the transition phase to active illness. The available evidence suggests that the left hippocampus is particularly vulnerable during these early stages, while further insult involving the hippocampus bilaterally occurs in those who develop a chronic form of the illness. CONCLUSIONS: Intervention strategies should target the most vulnerable stages of the illness, in particular the transition phase to psychosis, when novel treatments may prevent the illness or ameliorate its effects.

Brain↗
PubMed2000

Assessment of testicular core temperatures using microwave thermography.

A new method for the reliable assessment of testicular core temperature using microwave technology is presented. This study was designed to assess whether alterations in testicular thermoregulation could be reliably demonstrated in patients with clinically apparent varicoceles (n = 36), in those with idiopathic male infertility (n = 52) and in fertile donors (n = 20) using this new microwave thermographic technique. The measurements obtained were found to be reliable and reproducible. Testicular core temperature measurements were significantly different between the groups (P < 0.001). Furthermore, there was a temperature gradient between the scrotal neck and the testicular core in all groups; testicular core temperatures were lower than scrotal neck temperatures. The magnitude of this temperature difference was also significantly different (P < 0.001) between the groups. Microwave testicular thermography is a new technique that is safe and accurate. Preliminary results suggest altered testicular thermoregulation in a group of patients with impaired spermatogenesis with and without varicocele. Testicular temperature profiles obtained by microwave thermography may be of value in the assessment of infertile men with or without a varicocele.

Adult↗
PubMed2000

Hippocampal volume and everyday memory in children of very low birth weight.

Children born preterm and of very low birth weight have an increased incidence of learning difficulties, but little is known about the specific nature of their cognitive deficits and the underlying neuropathology. We hypothesized that their vulnerability to hypoxic, metabolic, and nutritional insults would lead to reduced hippocampal volumes and to deficits in memory because of the role of the hippocampus in this domain of cognition. Neuropsychological and magnetic resonance imaging methods were used to investigate this hypothesis in adolescents born preterm (< or = 30 wk gestation, n = 11) or full-term (n = 8). The preterm group had significantly smaller hippocampal volumes bilaterally, despite equivalent head size, and showed specific deficits in certain aspects of everyday memory, both on objective testing and as indicated by parental questionnaires. The preterm group also had a specific deficit in numeracy. The reduced hippocampal volumes and deficits in everyday memory have previously been unrecognized, but their prevalence in a group of neurologically normal children is striking.

Adolescent↗
PubMed2000

The incidence and significance of testicular microlithiasis in a subfertile population.

The objective of this study was to assess the frequency of testicular microlithiasis (TM) in infertile men who underwent testicular ultrasound and to determine any causative or associated factors. The case notes of 159 consecutive patients who were referred for testicular ultrasound in the investigation of male factor infertility were reviewed. Microcalcification was found in 10 cases (6.2%). This was unilateral in all cases and six patients had clinical evidence of a varicocele. Five cases had minimal calcification and five had marked TM. On patient had a past history of testicular maldescent and another of testicular torsion. Sperm function (as assessed by sperm count, motility and the sperm migration test) was variable within the 10 patients and there was no correlation with hormone profiles or testicular size. There was a statistical difference between a number of investigations in those patients with minimal degrees of calcification and those with TM (sperm migration test (SMT), namely sperm migration and sperm motility (p < 0.05, Mann-Whitney U test)). The results showed a higher than expected incidence of TM. Patients with marked TM seemed to have poorer sperm function than those with minimal calcification. There was a high incidence of co-existing pathology, for instance scrotal varicocele and cryptorchidism, although the numbers in this study were small and further studies need to be carried out to determine the exact nature and significance of this condition.

Gonadal Steroid Hormones↗
PubMed1999

Laterality of expression in portraiture: putting your best cheek forward.

Portraits, both photographic and painted, are often produced with more of one side of the face showing than the other. Typically, the left side of the face is overrepresented, with the head turned slightly to the sitter's right. This leftward bias is weaker for painted male portraits and non-existent for portraits of scientists from the Royal Society. What mechanism might account for this bias? Examination of portraits painted by left- and right-handers and of self-portraits suggests that the bias is not determined by a mechanical preference of the artist or by the viewer's aesthetics. The leftward bias seems to be determined by the sitters and their desire to display the left side of their face, which is controlled by the emotive, right cerebral hemisphere. When we asked people to portray as much emotion as possible when posing for a family portrait, they tended to present the left side of their face. When asked to pose as scientists and avoid portraying emotion, participants tended to present their right side. The motivation to portray emotion, or conceal it, might explain why portraits of males show a reduced leftward bias, and also why portraits of scientists from the Royal Society show no leftward bias.

Adult↗
PubMed1999

alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major components of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD. alpha-Synuclein fibrils similar to the Lewy body filaments can be formed in vitro, and we have shown recently that both PD-linked mutations accelerate their formation. This study addresses the mechanism of alpha-synuclein aggregation: we show that (i) it is a nucleation-dependent process that can be seeded by aggregated alpha-synuclein functioning as nuclei, (ii) this fibril growth follows first-order kinetics with respect to alpha-synuclein concentration, and (iii) mutant alpha-synuclein can seed the aggregation of wild type alpha-synuclein, which leads us to predict that the Lewy bodies of familial PD patients with alpha-synuclein mutations will contain both, the mutant and the wild type protein. Finally (iv), we show that wild type and mutant forms of alpha-synuclein do not differ in their critical concentrations. These results suggest that differences in aggregation kinetics of alpha-synucleins cannot be explained by differences in solubility but are due to different nucleation rates. Consequently, alpha-synuclein nucleation may be the rate-limiting step for the formation of Lewy body alpha-synuclein fibrils in Parkinson's disease.

Escherichia coli↗
PubMed1999

Inhibition of fibril formation in beta-amyloid peptide by a novel series of benzofurans.

A series of benzofuran derivatives have been identified as inhibitors of fibril formation in the beta-amyloid peptide. The activity of these compounds has been assessed by a novel fibril-formation-specific immunoassay and for their effects on the production of a biologically active fibril product. The inhibition afforded by the compounds seems to be associated with their binding to beta-amyloid, as identified by scintillation proximity binding assay. Binding assays and NMR studies also indicate that the inhibition is associated with self-aggregation of the compounds. There is a close correlation between the activity of the benzofurans as inhibitors of fibril formation and their ability to bind to beta-amyloid. Non-benzofuran inhibitors of the fibril formation process do not seem to bind to the same site on the beta-amyloid molecule as the benzofurans. Thus a specific recognition site might exist for benzofurans on beta-amyloid, binding to which seems to interfere with the ability of the peptide to form fibrils.

Amyloid beta-Peptides↗
PubMed1999

Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation.

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.

Cell Line↗
PubMed1999

Effects of body orientation and rotation axis on pitch visual-vestibular interaction.

Spatial transformations of the vestibular-optokinetic system must account for changes in head position with respect to gravity in order to produce compensatory oculomotor responses. The purpose of this experiment was to study the influence of gravity on the vestibulo-ocular reflex (VOR) in darkness and on visual-vestibular interaction in the pitch plane in human subjects using two different comparisons: (1) Earth-horizontal axis (EHA) rotation about an upright versus a supine body orientation, and (2) Earth-horizontal versus Earth-vertical (EVA) rotation axes. Visual-vestibular responses (VVR) were evaluated by measuring the slow phase velocity of nystagmus induced during sinusoidal motion of the body in the pitch plane (at 0.2 Hz and 0.8 Hz) combined with a constant-velocity vertical optokinetic stimulation (at +/- 36 degrees/s). The results showed no significant effect on the gain or phase of the VOR in darkness or on the VVR responses at 0.8 Hz between EHA upright and EHA supine body orientations. However, there was a downward shift in the VOR bias in darkness in the supine orientation. There were systematic changes in VOR and VVR between EHA and EVA for 0.2 Hz, including a reduced modulation gain, increased phase lead, and decreased bias during EVA rotation. The same trend was also observed at 0.8 Hz, but at a lesser extent, presumably due to the effects of eccentric rotation in our EVA condition and/or to the different canal input across frequencies. The change in the bias at 0.2 Hz between rotation in darkness and rotation with an optokinetic stimulus was greater than the optokinetic responses without rotation. During EHA, changes in head position relative to gravity preserve graviceptor input to the VVR regardless of body orientation. However, the modifications in VVR gain and phase when the rotation axis is aligned with gravity indicate that this graviceptive information is important for providing compensatory eye movements during visual-vestibular interaction in the pitch plane.

Adult↗
PubMed1999

Yaw and pitch visual-vestibular interaction in weightlessness.

Both yaw and pitch visual-vestibular interactions at two separate frequencies of chair rotation (0.2 and 0.8 Hz) in combination with a single velocity of optokinetic stimulus (36 degrees/s) were used to investigate the effects of sustained weightlessness on neural strategies adopted by astronaut subjects to cope with the stimulus rearrangement of spaceflight. Pitch and yaw oscillation in darkness at 0.2 and 0.8 Hz without optokinetic stimulation, and constant velocity linear optokinetic stimulation at 18, 36, and 54 degrees/s presented relative to the head with the subject stationary, were used as controls for the visual-vestibular interactions. The results following 8 days of space flight showed no significant changes in: (1) either the horizontal and vertical vestibulo-ocular reflex (VOR) gain, phase, or bias; (2) the yaw visual-vestibular response (VVR); or (3) the horizontal or vertical optokinetic (OKN) slow phase velocity (SPV). However, significant changes were observed: (1) when during pitch VVR at 0.2 Hz late inflight, the contribution of the optokinetic input to the combined oculomotor response was smaller than during the stationary OKN SPV measurements, followed by an increased contribution during the immediate postflight testing; and (2) when during pitch VVR at 0.8 Hz, the component of the combined oculomotor response due to the underlying vertical VOR was more efficiently suppressed early inflight and less suppressed immediately postflight compared with preflight observations. The larger OKN response during pitch VVR at 0.2 Hz and the better suppression of VOR during pitch VVR at 0.8 Hz postflight are presumably due to the increased role of vision early inflight and immediately after spaceflight, as previously observed in various studies. These results suggest that the subjects adopted a neural strategy to structure their spatial orientation in weightlessness by reweighting visual, otolith, and perhaps tactile/somatic signals.

Electrooculography↗
PubMed1998

An early stage in sodium channel clustering at developing rat neuromuscular junctions.

Voltage-gated sodium channels (VGSCs) are concentrated in the postsynaptic membrane at the adult rat neuromuscular junction (NMJ). We have used immunolabelling to determine the pattern of initial VGSC accumulation during development. At birth, but not 3 days before, VGSC labelling is detectable at the NMJ and in the perijunctional (periJ) membrane but not elsewhere. A much higher density cluster of VGSCs forms at the NMJ itself 1-2 weeks later. If the nerve is cut 2 days after birth, VGSC labelling persists in the periJ region for at least 4 weeks but the clustering of VGSCs at the NMJ fails to develop. Thus an early, stable accumulation of VGSCs develops near the NMJ at least a week before high density postsynaptic VGSC clusters form.

Animals↗