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Biomedical subjects

G Matthews

Publications and source records attributed to G Matthews.

At least 19 recordsLinked to original sources
PubMed1998

BMP1-related metalloproteinases promote the development of ventral mesoderm in early Xenopus embryos.

Bone morphogenetic protein 1 (BMP1) is a metalloproteinase closely related to Drosophila Tolloid (Tld). Tld regulates dorsoventral patterning in early Drosophila embryos by enhancing the activity of Dpp, a member of the TGF-beta family most closely related to BMP2 and BMP4. In Xenopus BMP4 appears to play an essential role in dorsoventral patterning, promoting the development of ventral fates during gastrula stages. To determine if BMP1 has a role in regulating the activity of BMP4, we have isolated cDNAs for Xenopus BMP1 and a novel closely related gene that we have called xolloid (xld). Whereas xbmp1 is uniformly expressed at all stages tested, the initial uniform expression of xld becomes localized to two posterior ectodermal patches flanking the neural plate and later to the inner ectoderm of the developing tailbud. xld is also expressed in dorsal regions of the brain during tailbud stages and is especially abundant in the ventricular layer of the dorsal hindbrain caudal to the otic vesicle. Overexpression of either gene inhibits the development of dorsoanterior structures in whole embryos and ventralizes activin-induced dorsal mesoderm in animal caps. Since ventralization of activin-induced animal caps can be blocked by coinjecting a dominant-inhibitory receptor for BMP2 and BMP4, we suggest a role for BMP1 and Xld in regulating the ventralizing activity of these molecules.

Activins↗
PubMed1998

Rehabilitation in an individual with chronic arsenic poisoning: medical, psychological, and social implications.

Although arsenic poisoning was a common cause of homicide in the past, it is seldom suspected today; thus there may be serious delays in diagnosis and treatment of arsenic ingestion. Rehabilitation specialists have traditionally dealt with the debilitating consequences of the classic arsenic-induced sensorimotor peripheral neuropathy; however, a knowledge of the presentation of acute toxicity combined with the effects of chronic exposure is essential for proper treatment, particularly in the event of ongoing exposure. This case report demonstrates the wide spectrum of medical complications associated with arsenic poisoning and briefly reviews its pathophysiology and treatment from both the medical and psychosocial perspective.

Adult↗
PubMed1998

Driver stress and performance on a driving simulator.

Effects of stress on driving performance can depend on the nature of driver's stress reactions and on the traffic environment. In an experimental study, we assessed multiple dimensions of vulnerability to driver stress by a questionnaire that was validated in previous field studies and related those dimensions to performance on a driving simulator. Results were broadly consistent with prediction. A dimension of habitual dislike of driving was associated with reduced control skills, greater caution, and disturbance of moods. A measure of aggressive driving predicted more frequent and more error-prone overtaking, which are effects attributed to the use of confrontive coping strategies in interaction with other vehicles. An alertness measure predicted speed of reaction to pedestrian hazards. This research has practical applications for system design, automated monitoring of driver performance, selection and assessment of drivers, and training.

Adolescent↗
PubMed1997

Depletion and replenishment of vesicle pools at a ribbon-type synaptic terminal.

Synaptic depression was studied using capacitance measurements in synaptic terminals of retinal bipolar neurons. Single 250 msec depolarizations evoked saturating capacitance responses averaging approximately 150 fF, whereas trains of 250 msec depolarizations produced plateau capacitance increases of approximately 300 fF. Both types of stimuli were followed by pronounced synaptic depression, which recovered with a time constant of approximately 8 sec after single pulses but required >20 sec for full recovery after pulse trains. Inactivation of presynaptic calcium current could not account for depression, which is attributed instead to depletion of releasable and reserve vesicle pools that are recruited and replenished at different rates. Recovery from depression was normal in the absence of fast endocytosis, suggesting that replenishment was from a reserve pool of preformed vesicles rather than from preferential recycling of recently fused vesicles. Given the in vivo light response of the class of bipolar neuron studied here, it is likely that, under at least some illumination conditions, the cells produce a fast and phasic bout of exocytosis rather than tonic release.

Animals↗
PubMed1997

Implications of task-induced fatigue effects for in-vehicle countermeasures to driver fatigue.

Two driving simulator studies are reported which investigate the variation of fatigue effects with task demands and provide recommendations for system design to counteract driver fatigue. Two opposing explanations of the interactive effects of task demands and fatigue were examined. One explanation is that fatigue drains attentional resources, so that detrimental effects of fatigue on performance are accentuated when task demands increase. The alternative explanation is that fatigue disrupts matching of effort to task demands, such that the fatigued driver fails to regulate effort effectively when the task appears easy. In both studies, drivers performed both a fatiguing drive, in the first part of which they were required to perform a secondary detection task, and a control drive with no additional secondary task. In the last part of both drives, drivers were required to detect movement in pedestrian stimuli presented on both sides of the road. Vehicle control and steering movements were logged throughout both drives. The results are consistent with dynamic models of stress and sustained performance which suggest that fatigue may impair adaptation to conditions of underload, but are inconsistent with the attentional resource explanation. These task-specific fatigue effects have important implications for in-vehicle countermeasures to driver fatigue. Current approaches to the implementation of such devices fail to reflect the task-specific nature of fatigue effects. Fatigue-monitoring devices may only be valid in certain driving environments or contexts. Hence, it may be necessary to integrate performance-based feedback monitoring information with route and traffic density information from navigation systems.

Adaptation, Psychological↗
PubMed1997

Static and dynamic membrane properties of large-terminal bipolar cells from goldfish retina: experimental test of a compartment model.

Capacitance measurements allow direct studies of exocytosis and endocytosis in single synaptic terminals isolated from bipolar neurons of goldfish retina. Extending the technique to intact bipolar cells, with their more complex morphology, requires information about the cells' electrotonic architecture. To this end, we developed a compartment model of bipolar neurons isolated from goldfish retina and tested the model experimentally. The isolated cells retained morphology similar to that of bipolar neurons in intact goldfish retina. In whole cell recordings, current relaxations in response to 10-mV hyperpolarizing voltage pulses decayed with a biexponential time course. This suggests that the cells may be described by a two-compartment equivalent circuit with compartments corresponding to the soma/dendrites (6-10 pF) and synaptic terminal (2-4 pF), linked by the axial resistance (30-60 M omega) of the axon. Four lines of evidence validate the equivalent circuit. 1) Similar estimates of somatic/dendritic and terminal capacitance were obtained whether the patch pipette was attached to the soma or to the synaptic terminal. 2) Estimates of the capacitance of the two compartments in intact cells were similar to estimates from somata and terminals that were isolated by cleavage of the connecting axon. 3) When current transients were generated from a more complete computer simulation of a bipolar neuron, analysis of the simulated transients with the use of the simple two-compartment model yielded capacitance estimates similar to those used to set up the simulation. 4) In isolated cells, the model gave estimates of depolarization-evoked increases in capacitance of the synaptic terminal that were quantitatively similar to those measured in terminals that were detached from the rest of the cell. Although in previous studies researchers have attempted to apply a similar equivalent circuit to more geometrically complex cells, morphological correlates of the equivalent-circuit compartments have been elusive. Our results demonstrate that in dissociated bipolar cells, precise morphological correlates can be assigned to the equivalent-circuit compartments. Additionally, the work shows that time-resolved capacitance measurements of synaptic transmitter release are possible in intact, isolated bipolar neurons and may also be feasible in intact tissue.

Animals↗
PubMed1996

Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released.

We relate the ultrastructure of the giant bipolar synapse in goldfish retina to the jump in capacitance that accompanies depolarization-evoked exocytosis. Mean vesicle diameter is 29 +/- 4 nm, giving 26.4 aF/vesicle, so the maximum evoked capacitance (150 fF within 200 ms) represents fusion of about 5700 vesicles. Two terminals contained, respectively, 45 and 65 ribbon-type synaptic outputs, and a fully loaded ribbon tethers about 110 vesicles. Thus, the tethered pool, about 6000 vesicles, corresponds to the rapidly released pool. Further, the difference between small and large terminals in number of tethered vesicles matches their difference in capacitance jump. This suggests, within a "fire and reload" model of exocytosis, that the ribbon translocates synaptic vesicles very rapidly to membrane docking sites, supporting a maximum release rate of 500 vesicles/active zone/s, until the population of tethered vesicles is exhausted.

Animals↗
PubMed1996

Ultrafast exocytosis elicited by calcium current in synaptic terminals of retinal bipolar neurons.

Using high resolution capacitance measurements, we have characterized an ultrafast component of transmitter release in ribbon-type synaptic terminals of retinal bipolar neurons. During depolarization, capacitance increases to a plateau of approximately 30 fF with a time constant of approximately 1.5 ms. When not limited by activation kinetics of calcium current, the small pool is depleted even faster, with a time constant of 0.5 ms. After the ultrafast pool is depleted, capacitance rises with a slower time constant of approximately 300 ms. EGTA (5 mM) depresses the slower capacitance rise but leaves the ultrafast phase intact. BAPTA (5 mM) depresses both components of exocytosis. With paired-pulse stimulation, the ultrafast pool recovers from depletion with a time constant of approximately 4 s. The ultrafast component may represent fusion of docked vesicles at the base of the synaptic ribbon, while the slower component represents more distal vesicles on the ribbon.

Animals↗
PubMed1996

Synaptic exocytosis and endocytosis: capacitance measurements.

Exo- and endocytosis are accompanied by changes in membrane capacitance. Capacitance measurements in synaptic terminals have proven recently to be a useful adjunct to other techniques in examining presynaptic mechanisms. New information has emerged from these studies about the size and dynamics of synaptic vesicle pools, about the Ca2+ dependence of the rate of exocytosis, and about the kinetics of endocytosis in synaptic terminals.

Animals↗
PubMed1996

Laparoscopic cholecystectomy for recurrent gallstone pancreatitis during pregnancy.

A pregnant patient with gallstone-induced pancreatitis initially responded to medical treatment, but the pancreatitis recurred. Endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy were done at 28 weeks' gestation. The remainder of the pregnancy was unremarkable. Although 20 cases of laparoscopic cholecystectomy have been reported for cholecystitis during pregnancy, this is the first report of laparoscopic management of recurrent gallstone pancreatitis in a pregnant patient.

Adult↗
PubMed1996

Age and gender differences in perceived accident likelihood and driver competences.

Road traffic accident involvement rates show clear age and gender differences which may in part be accounted for by differences in risk perception and perceptions of driving competence. The present study extends and replicates that of Matthews and Moran (1986). Young (18-30 years) and older (45-60 years) male and female drivers responded to a questionnaire on perceived accident risk and driving competence (judgment and skill) with respect to themselves and four target groups, and also rated a series of videotaped driving sequences with respect to likelihood of accident occurrence and perceived driving competence. Results showed that effects of rater characteristics were generally confined to the questionnaire. Younger males were perceived as most likely to experience an accident and were judged to be lower than other groups in driving competence. Younger groups showed little bias against older groups and vice versa, but gender-related bias was apparent. The findings of Matthews and Moran were generally confirmed. The results are discussed with reference to four main issues: (1) demographic bias effects--which are generally weak; (2) stereotyping on the basis of gender and/or age of driver; (3) group-specific bias; (4) self-appraisal bias.

Accidents, Traffic↗
PubMed1996

Neurotransmitter release.

Synaptic vesicle exocytosis is rapid and highly localized, which are features that arise from the organization of the presynaptic active zone, where vesicle fusion occurs. Colocalization of calcium channels with the proteins making up the vesicle docking machinery at the active zone, combined with the low affinity and high cooperativity of the calcium sensor for vesicle fusion, allows vesicles to fuse with short delay after a presynaptic action potential. Evidence suggests that the calcium concentration driving synaptic vesicle fusion corresponds to the high level (50-100 muM) achieved only within the microdomain of elevated calcium near the inner mouth of open calcium channels. Retrieval of synaptic vesicle membrane by endocytosis is also regulated by internal calcium but at much lower concentrations. Endocytosis occurs rapidly after exocytosis if internal calcium is near the basal level but is inhibited by elevated internal calcium (0.5-1.0 muM).

Action Potentials↗
PubMed1996

Calcium-dependent inactivation of calcium current in synaptic terminals of retinal bipolar neurons.

Giant synaptic terminals (approximately 10 micrometer diameter) of bipolar neurons from goldfish retina were used to directly investigate calcium-dependent inactivation of presynaptic calcium current. During sustained depolarization, calcium current was initially constant for a period lasting up to several hundred milliseconds and then it declined exponentially. The duration of the initial delay was shorter and the rate of inactivation was faster with larger calcium current. The fastest time constant of inactivation (in the range of 2-5 sec) was observed under weak calcium buffering conditions. Inactivation was attenuated when external Ca2+ was replaced with Ba2+ and when terminals were dialyzed with high concentrations of internal BAPTA. Elevation of intracellular calcium concentration ([Ca2+]i) by application of the calcium ionophore ionomycin or by dialysis with pipette solutions containing buffered elevated [Ca2+] produced inactivation of calcium current. The rate of recovery from inactivation was not determined by the recovery of [Ca2+]i to baseline after a stimulus. The results demonstrate that the presynaptic calcium current in bipolar neurons is inactivated by elevated [Ca2+]i, but the inactivation is approximately 100-fold slower than previously described calcium-dependent inactivation in other types of cells.

Animals↗
PubMed1995

Differences in pH optima and calcium requirements for maturation of the prohormone convertases PC2 and PC3 indicates different intracellular locations for these events.

PC2 and PC3, which is also known as PC1, are subtilisin-like proteases that are involved in the intracellular processing of prohormones and proneuropeptides. Both enzymes are synthesized as propolypeptides that undergo proteolytic maturation within the secretory pathway. An in vitro translation/translocation system from Xenopus egg extracts was used to investigate mechanisms in the maturation of pro-PC3 and pro-PC2. Pro-PC3 underwent rapid (t1/2 < 10 min) processing of the 88-kDa propolypeptide at the sequence RSKR83 to generate the 80-kDa active form of the enzyme. This processing was blocked when the active site aspartate was changed to asparagine, suggesting that an autocatalytic mechanism was involved. In this system, processing of pro-PC3 was optimal between pH 7.0 and 8.0 and was not dependent on additional calcium. These results are consistent with pro-PC3 maturation occurring at an early stage in the secretory pathway, possibly within the endoplasmic reticulum, where the pH would be close to neutral and the calcium concentration less than that observed in later compartments. Processing of pro-PC2 in the Xenopus egg extract was much slower than that of pro-PC3 (t1/2 = 8 h). It exhibited a pH optimum of 5.5-6.0 and was dependent on calcium (K0.5 = 2-4 mM). The enzymatic properties of pro-PC2 processing were similar to that of the mature enzyme. Further studies using mutant pro-PC2 constructs suggested that cleavage of pro-PC2 was catalyzed by the mature 68-kDa PC2 molecule. The results were consistent with pro-PC2 maturation occurring within a late compartment of the secretory pathway that contains a high calcium concentration and low pH.

Amino Acid Sequence↗