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M J Webster

Publications and source records attributed to M J Webster.

At least 37 records · Page 2Linked to original sources

Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia.

Schizophrenia has been associated with anatomical and functional abnormalities of the dorsolateral prefrontal cortex (DLPFC), which may reflect abnormal connections of DLPFC neurons. We measured mRNA levels of growth-associated protein (GAP-43), a peptide linked to the modifiability of neuronal connections, in post-mortem brain tissue from two cohorts of patients with schizophrenia and controls. Using the RNase protection assay (RPA), we found a significant reduction in GAP-43 mRNA in the DLPFC, but not in the hippocampus, of patients with schizophrenia. With in situ hybridization histo- chemistry (ISHH), performed on a separate cohort, we confirmed the reduction of GAP-43 mRNA in the DLPFC of patients with schizophrenia. We detected reduced GAP-43 mRNA per neuron in layers III, V and VI of patients with schizophrenia compared with normal controls and patients with bipolar disorder. Thus, glutamate neurons in DLPFC of schizophrenic patients may synthesize less GAP-43, which could reflect fewer and/or less modifiable connections than those in normal human brain, and which may be consistent with the deficits of prefrontal cortical function that characterize schizophrenia.

Adult↗

Effectiveness of glycerol as a rehydrating agent.

On two occasions, 8 male subjects completed a dehydration protocol, immediately followed by a 180-min rehydration protocol, then a subsequent exercise bout. During each dehydration session, subjects lost 3.1 +/- 0.4% body weight (BW) following discontinuous exercise in the heat (40 degreesC, 33% rh). During the first 30 min of rehydration, subjects ingested either 1.0-g glycerol x kg body weight(-1) + 30% of the total rehydration water volume (GLY), or 30% of the total rehydration water volume without glycerol (CON). The five remaining ingestions (every 30 min) were equal to 14% of the remaining fluid volume and were identical in nature. Fluid volume ingested equaled fluid volume lost during dehydration. Following the 180 min rehydration period, subjects cycled (appoximately 50% VO2 peak) in the heat (40 degrees C, 33% rh) until volitional exhaustion. Three observations were made: (a) Following glycerol-induced rehydration, time to volitional exhaustion was greater during the subsequent exercise bout in the heat (CON: 38.0 +/- 2.0, GLY 42.8 +/- 1.0 min, p <.05); (b) glycerol-induced rehydration significantly increased plasma volume restoration within 60 min and at the end of the 180-min rehydration period; and (c) total urine volume was lower and percent rehydration was greater following GLY, but neither was significantly different.

Adult↗

Localization of epidermal growth factor receptors and putative neuroblasts in human subependymal zone.

Studies in rodents and monkeys suggest that neuronal precursor cells continue to exist and differentiate well into adulthood in these species. These results challenge the long held assumption that neurogenesis does not occur in the postnatal human brain. We examined the rostral subependymal zone (SEZ) of postnatal human brain for expression of cell phenotypic markers that have been associated with neuronal precursors and neuroblasts in rodent brain. We found epidermal growth factor receptor (EGF-R) mRNA and protein to be expressed in infant, teen, young adult, and adult human SEZ. Some SEZ cells expressed the polysialic acid form of neural cell adhesion molecule (PSA-NCAM), characteristic of migrating neuroblasts, as well as class III beta-tubulin and Hu protein, characteristic of neuroblasts and early neurons. These neuroblast-like cells were negative for glial fibrillary acidic protein (GFAP), 2;,3;-cyclic nucleotide 3;-phosphohydrolase (CNPase), and vimentin, suggesting that they were not differentiating as glia. Our results show that neuroblast-like cells exist in the human SEZ and support the theory that SEZ of postnatal human brain has neurogenic potential.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Visual cortical projections and chemoarchitecture of macaque monkey pulvinar.

We investigated the patterns of projections from the pulvinar to visual areas V1, V2, V4, and MT, and their relationships to pulvinar subdivisions based on patterns of calbindin (CB) immunostaining and estimates of visual field maps (P(1), P(2) and P(3)). Multiple retrograde tracers were placed into V1, V2, V4, and/or MT in 11 adult macaque monkeys. The inferior pulvinar (PI) was subdivided into medial (PI(M)), posterior (PI(P)), central medial (PI(CM)), and central lateral (PI(CL)) regions, confirming earlier CB studies. The P(1) map includes PI(CL) and the ventromedial portion of the lateral pulvinar (PL), P(2) is found in ventrolateral PL, and P(3) includes PI(P), PI(M), and PI(CM). Projections to areas V1 and V2 were found to be overlapping in P(1) and P(2), but those from P(2) to V2 were denser than those to V1. V2 also received light projections from PI(CM) and, less reliably, from PI(M). Neurons projecting to V4 and MT were more abundant than those projecting to V1 and V2. Those projecting to V4 were observed in P(1), densely in P(2), and also in PI(CM) and PI(P) of P(3). Those projecting to MT were found in P(1)- P(3), with the heaviest projection from P(3). Projections from P(3) to MT and V4 were mainly interdigitated, with the densest to MT arising from PI(M) and the densest to V4 arising from PI(P) and PI(CM). Because the calbindin-rich and -poor regions of P(3) corresponded to differential patterns of cortical connectivity, the results suggest that CB may further delineate functional subdivisions in the pulvinar.

Animals↗

The effect of siberian ginseng (Eleutherococcus senticosus) on substrate utilization and performance.

It has been suggested that Eleutherococcus senticosus (ES), also known as Siberian ginseng or ciwuija, increases fat utilization in humans. The purpose of this study was to examine the physiological responses to supplementation with ES in endurance cyclists. Using a randomized, double-blind crossover design, 9 highly-trained men (28 +/- 2 years, VáO2max 57.3 +/- 2.0 ml á kg-1 á min-1) cycled for 120 min at '60% VáO2max followed by a simulated 10-km time trial. Diet was controlled, and ES (1,200 mg á day-1) or a placebo (P) were administered for 7 days prior to each of the two trials. Oxygen consumption, respiratory exchange ratio, and heart rate were recorded every 30 min, and rating of perceived exertion, plasma [lactate], and plasma [glucose] were recorded every 20 min during the 120 min of steady state cycling. There were no significant differences (p >.05) between the ES and P groups at any steady-state time interval or during the cycling time trial (ES = 18.10 +/- 0.42, P = 17.83 +/- 0.47 min). In contrast with previous reports, the results of this study suggest that ES supplementation does not alter steady-state substrate utilization or 10-km cycling performance time.

Adult↗

Immunohistochemical localization of the cell adhesion molecules Thy-1 and L1 in the human prefrontal cortex patients with schizophrenia, bipolar disorder, and depression.

L1 and Thy-1 are members of the immunoglobulin (Ig) superfamily of cell adhesion molecules (CAMs) that are vital for normal neural development. Abnormalities in CAM expression could lead to the histological abnormalities that have previously been described in the frontal cortex of patients with schizophrenia. A postmortem immunohistochemical study of L1 and Thy-1 in the normal human prefrontal cortex revealed positive immunostaining of axons in all layers of the cortex. Quantifying the intensity of immunostaining in the prefrontal cortex of patients with schizophrenia, bipolar disorder and depression failed to reveal any significant differences when compared to that of normal controls.

Adult↗

VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia.

The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE-immunoreactive proteins that also reacted to an N-CAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders.

Bipolar Disorder↗

Physiological and performance responses to supplementation with thiamin and pantothenic acid derivatives.

The purpose of this study was to investigate the physiological and performance responses to supplementation with allithiamin and pantethine. On two separate occasions, six highly trained cyclists [maximum O2 consumption or VO2max 61.8 (2.1) ml x kg(-1) x min(-1)] performed a 50-km steady-state ride on a cycle ergometer at a workload corresponding to approximately 60% of VO2max followed by a 2000-m time trial. For 7 days prior to each ride, subjects daily ingested either a placebo (PL) or a combination of 1 g of allithiamin and 1.8 g of a 55%/45% pantethine/pantothenic acid compound (AP). Treatments were administered using a randomized, double-blind, counter-balanced design. During the 50km ride, measures of heart rate, respiratory gas exchange and ratings of perceived exertion were recorded at 5, 15, 25, 35 and 45 km. Blood samples were collected at 10, 20, 30, 40 and 50 km and analyzed for lactate, glucose and free fatty acids. Blood samples for the analysis of lactate were also collected 3 and 5 min after the completion of the 2000-m time trial. There were no significant differences in any of the measured parameters between experimental conditions. Time to complete the 2000-m time trial was also not significantly different between experimental conditions [PL 178.2 (8.4), AP 170.7 (10.2) s; P=0.58]. These results suggest that, despite the reported enhanced absorption properties, supplementation with allithiamin and pantethine does not alter exercise metabolism or exercise performance.

Adult↗

Effect of induced alkalosis on exhaustive leg press performance.

PURPOSE: Fifteen males were studied before, during, and in recovery from exhaustive resistance exercise 105 min after ingesting 0.3 g.kg-1 of either a placebo (white flour) or sodium bicarbonate (NaHCO3). METHODS: The exercise consisted of five maximal sets on a leg press machine, The load was adjusted to maintain the number of repetitions per set for each subject at approximately 12 repetitions. A significant (P < 0.05) increase in pH (7.40 to 7.47), oxygenated base excess (OxyBE) (-1.3 to 4.0 mEq.L-1), and bicarbonate concentration ([HCO3-]) (22.8 to 27.4 mM) was achieved before exercise with the ingestion of NaHCO3. RESULTS: The exercise protocol produced significant changes in acid base status consistent with metabolic acidosis for both trials (pH sets 1-5: placebo, 7.4 to 7.26; NaHCO3, 7.47 to 7.33), (OxyBE sets 1-5: placebo, -1.3 to -12.3 mEq.L-1; NaHCO3, 4.0 to -6.9 mEq.L-1) and ([HCO3-] sets 1-5: placebo, 22.9 to 14.0 mM; NaHCO3, 27.4 to 17.6 mM). After every set; pH, OxyBE, and [HCO3-] were significantly higher in the NaHCO3 trial. Blood lactate concentration ([La-]) significantly increased throughout exercise for both trials ([La-] sets 1-5: placebo, 4.6 to 11.3 mM; NaHCO3, 4.8 to 13.4 mM). After sets 4 and 5, blood [La-] was significantly higher in the NaHCO3 trial. Bicarbonate ingestion did not improve performance (total repetitions: NaHCO3 = 59 +/- 3; placebo = 60 +/- 2). CONCLUSIONS: This may be a result of a lower demand on the whole body metabolic system in comparison with that for other modes of exercise in which ergogenic effects have been found.

Adult↗

Acute L-glutamine ingestion does not improve maximal effort exercise.

BACKGROUND: L-glutamine (GLN) may have an ergogenic effect during exercise considering its base generating potential. We attempted to determine whether GLN ingestion influences acid-base balance and improves high intensity exercise performance. METHOD: Ten trained males performed five exercise bouts on a cycle ergometer at 100% of VO2 peak. The first four bouts were 60 sec in duration, while the fifth bout was continued to fatigue. Each bout was separated by 60 sec of recovery. The exercise bouts were initiated 90 min after ingesting 0.03 g.kg body mass-1 of either GLN or placebo (PLC). Venous blood samples were collected pre-ingestion (PRE-IN), pre-exercise (PRE-EX), and following bouts four (B4) and five (B5) and analyzed for pH, bicarbonate concentration (HCO3), and lactate concentration (La-). Time to fatigue for B5 was used as a performance measure. RESULTS: pH, [HCO3], and [La-] were not significantly different (p > 0.05) between conditions for PRE-IN, PRE-EX, B4, and B5. Time to fatigue was not significantly different between conditions and averaged 263.4 +/- 24.5 sec and 263.2 +/- 19.4 sec for the GLN and PLC trials, respectively. CONCLUSIONS: These data indicate that acute ingestion of L-glutamine does not enhance either buffering potential or high intensity exercise performance in trained males.

Acid-Base Equilibrium↗

The effect of a thiamin derivative on exercise performance.

The purpose of this study was to investigate the effect of a thiamin derivative, thiamin tetrahydrofurfuryl disulfide (TTFD), on oxygen uptake (VO2), lactate accumulation and cycling performance during exercise to exhaustion. Using a randomized, double-blind, cross-over design with a 10-day washout between trials, 14 subjects ingested either 1 g.day-1 of TTFD or a placebo (PL) for 4 days. On day 3, subjects performed a progressive exercise-test to exhaustion on a cycle ergometer for the determination of VO2submax, VO2peak, lactate concentration ([La-]), lactate threshold (ThLa) and heart rate (fc). On day 4, subjects performed a maximal 2000-m time trial on a cycle ergometer. A one-way analysis of variance (ANOVA) with repeated measures was used to determine significant differences between trials. There were no significant differences detected between trials for serial measures of VO2submax, [La-] or fc. Likewise, VO2peak [PL 4.06 (0.19) TTFD 4.12 (0.19) l.min-1, P = 0.83], ThLa [PL 2.47 (0.17), TTFD 2.43 (0.16) l.min-1, P = 0.86] and 2000-m performance time [PL 204.5 (5.5), TTFD 200.9 (4.3).s, P = 0.61] were not significantly different between trials. The results of this study suggest that thiamin derivative supplementation does not influence high-intensity exercise performance.

Adult↗

Allithiamine ingestion does not enhance isokinetic parameters of muscle performance.

The purpose of this study was to investigate the effect of oral allithiamine administration on isokinetic parameters of muscle performance and lactate accumulation prior to, during and in recovery from isokinetic exercise. A double-blind, counterbalanced, crossover experimental design utilizing a Biodex System 2 Isokinetic Dynamometer was used to test 15 healthy college students. Subjects orally ingested either 1 g. day-1 of a thiamin derivative, allithiamine, or placebo for 5 days and then performed six exercise sets of knee extension and flexion. ANOVA revealed no significant differences between treatment conditions in peak torque, mean peak torque, average power, or total work performed (p > .05). Likewise, lactate accumulation was not significantly different between treatment conditions at any measurement point (p > .05). The absence of significant differences suggests that oral allithiamine administration does not enhance isokinetic parameters of muscle performance or lactate accumulation prior to, during, and following isokinetic exercise.

Adult↗

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways.

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Animals↗

The effects of buffer ingestion on metabolic factors related to distance running performance.

We examined the effects of sodium bicarbonate (BIC) and sodium citrate (CIT) ingestion on distance running performance. Seven male runners [mean VO2max = 61.7 (SEM 1.7) ml.kg-1.min-1] performed three 30-min treadmill runs at the lactate threshold (LT) each followed by a run to exhaustion at 110% of LT. The runs were double-blind and randomly assigned from BIC (0.3 g.kg body mass-1), CIT (0.5 g.kg body mass-1) and placebo (PLC, wheat flour, 0.5 g.kg body mass-1). Venous blood samples were collected at 5, 15 and 25 min during the run and immediately post-exhaustion (POST-EX) and analysed for pH, and the concentrations of lactate ([la-]b) and bicarbonate ([HCO3-]). Performance was measured as running time to exhaustion at 110% of LT (TIME-EX). The pH was significantly higher (P < or = 0.05) for the BIC and CIT trials during exercise, but not POST-EX compared to PLC. The [la-]b was significantly higher (P < or = 0.05) for the CIT trial compared to PLC during exercise, and for both CIT and BIC compared to PLC at POST-EX. Blood [HCO3-] was significantly higher (P < or = 0.05) during exercise for BIC compared to PLC. TIME-EX was not significantly different among treatments: BIC 287 (SEM 47.4)s; CIT 172.8 (SEM 29.7)s; and PLC 222.3 (SEM 39.7)s. Despite the fact that buffer ingestion produced favourable metabolic conditions during 30 min of high intensity steady-state exercise, a significant improvement in the subsequent maximal exercise run to exhaustion did not occur.

Adult↗

Sodium citrate ingestion enhances 30 km cycling performance.

The purpose of this study was to examine the effects of sodium citrate (CIT) ingestion on 30 km cycling performance. Eight trained male cyclists (VO2max = 54.7 +/- 1.7 ml.kg-1.min-1) performed two 30 km cycling time trials. The trials were double blind and randomly assigned from CIT or placebo (PLC), with both dosages at 0.5 g.kg body wt-1. Blood samples were collected from an indwelling catheter at 10 km intervals and analyzed for PO2, PCO2, pH, and lactate concentration ([La]). Power output, heart rate (HR) and RPE were measured at 5 min intervals during the trials, while cycling performance was determined from time to complete the 30 km. A repeated measures ANOVA and dependent t-tests were used to locate differences between the trials. A significant difference (p < or = 0.01) was observed for pH and [La] during the trials with CIT being elevated above PLC throughout the ride. No significant differences (p > 0.01) were observed for any of the other dependent variables. However, power output and HR were slightly elevated during the CIT trial. Performance time was significantly faster (p < or = 0.05) for the CIT trial (3459.6 +/- 97.4 s) compared to the PLC trial (3562.3 +/- 108.5 s). The data indicate that favorable metabolic conditions were obtained following CIT ingestion and these likely contributed to the improvement in cycling performance.

Adult↗

Transient subcortical connections of inferior temporal areas TE and TEO in infant macaque monkeys.

As part of a long-term study designed to examine the ontogeny of visual memory in monkeys and its underlying neural circuitry, we have examined the subcortical connections of the inferior temporal cortex in infant monkeys and compared them to those previously described in adult monkeys (Webster et al. [1993] J. Comp. Neurol. 335:73-91). Inferior temporal areas TEO and TE were injected with wheat germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids, respectively, or vice versa, in 1-week-old (N = 6) and 3-4-year-old (N = 6) Macaca mulatta, and the distributions of labeled cells and terminals were examined in subcortical structures. Although the connections of inferior temporal cortex with subcortical structures were found to be similar in infant and adult monkeys, several projections appear to undergo refinement during development. Quantitative analysis showed that 1) whereas the projection from TE to the superior colliculus is consistent (5 of 5 cases) and widespread in infants, it is less reliable (2 of 7 cases) and limited in areal extent in adults; 2) although the projections from TE to nucleus medialis dorsalis and the tail of the caudate are present in infants and adults, they are reduced in adults; and 3) TEO receives input from the dorsal lateral geniculate nucleus in both infants and adults, but the number of cells giving rise to this projection is lower in adults. There was also a suggestion that TE projects to nucleus paracentralis in infants (2 of 5 cases) but not in adults (0 of 7 cases). No differences between infants and adults were apparent in other subcortical connections, including those with the pulvinar, reticular nucleus, claustrum, and putamen.

Animals↗

Tissue-regulated differentiation and maturation of a v-abl-immortalized mast cell-committed progenitor.

An immature v-abl-transformed mast cell line (V3-MC) was derived from a mouse that developed systemic mastocytosis after transplantation of v-abl-infected bone marrow cells. V3-MCs injected intravenously into adult BALB/c mice infiltrated the liver, spleen, and intestine by day 6 and underwent progressive differentiation and maturation, eventually resembling indigenous mast cells. In terms of their protease content, the V3-MCs that localized in the liver and spleen differed from those in the intestine, and both differed from the cultured V3-MCs. The acquired expression of certain proteases and the loss of expression of other proteases in these tissue V3-MCs defines particular phenotypes and indicates that the differentiation and maturation of mast cell-committed progenitor cells are primarily regulated by factors in the different tissue microenvironments.

Animals↗

Development and plasticity of the neural circuitry underlying visual recognition memory.

In adult monkeys, visual recognition memory, as measured by the delayed nonmatching to sample (DNMS) task, requires the interaction between inferior temporal cortical area TE and medial temporal lobe structures (mainly the entorhinal and perirhinal cortical areas). Ontogenetically, monkeys do not perform at adult levels of proficiency on the DNMS task until 2 years of age. Recent studies have demonstrated that this protracted development of visual recognition memory is due to an immaturity of the association areas of the neocortex rather than the medial temporal lobe. For example, lesions of the medial temporal lobe structures in infancy or in adulthood yield profound and permanent visual recognition loss, indicating that the medial temporal lobe structures operate early in life to sustain visual memory. In contrast, early lesions of area TE, unlike late lesions, result in a significant and long-lasting sparing of visual memory ability. Further evidence for neocortical immaturity is provided by studies of the development of opiatergic and cholinergic receptors, of the maturation of metabolic activity, and of the connectivity between inferior temporal areas TE and TEO and cortical and subcortical structures. Together these results indicate greater compensatory potential after neonatal cortical than after neonatal medial temporal removals. In support of this view, early damage to area TE leads to the maintenance of normally transient projections as well as to reorganization in cortical areas outside the temporal lobe. In addition, lesion studies indicate that, during infancy, visual recognition functions are widely distributed throughout many visual association areas but, with maturation, these functions become localized to area TE. Thus, the maintenance of exuberant projections together with reorganization in other cortical areas of the brain could account for the preservation of visual memories in monkeys that have had area TE removed in infancy.

Animals↗