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Biomedical subjects

M J Webster

Publications and source records attributed to M J Webster.

54 records · Page 3Linked to original sources
PubMed1995

Rapid tracer lactate influx into canine skeletal muscle.

This study evaluated the effects of various lactate transport inhibitors and competitors on rapid tracer lactate influx into the canine gastrocnemius-plantaris muscle (GP). GPs of 25 anesthetized dogs were perfused with red blood cell-free media in situ. At 0.9 mM lactate concentration ([La]), GP oxygen uptake (2.6 +/- 0.1 ml.kg-1.min-1) and net lactate output (-0.039 +/- 0.007 mmol.kg-1.min-1) were similar to values during blood perfusion. Rapid tracer lactate influx was inferred by a paired-tracer dilution method at nominal perfusate [La] values of 1, 5, 10, 25, and 50 mM. The maximal tracer influx rate (Umax) decreased significantly with each increase in unlabeled [La]. A saturation effect was suggested by the fact that percent inhibition of Umax began to reach a plateau at the higher unlabeled [La] values. The inhibition of Umax was 20.5 +/- 2.9% at 5 mM, 34.1 +/- 3.3% at 10 mM, 47.3 +/- 2.7% at 25 mM, and 56.1 +/- 2.8% at 50 mM [La]. Umax was also inhibited by various inhibitors/competitors of lactate transport as follows (% inhibition): 50 mM alpha-cyano-4-hydroxy-cinnamate (69.2 +/- 4.9%), 1.5 mM phloretin (25.4 +/- 5.5%), 0.1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.3 +/- 1.9%), 0.5 mM p-chloromercuribenzenesulfonic acid (72.9%), 0.5 mM furosemide (+ 2.8%), 25 mM pyruvate (52.4 +/- 2.9%), and 50 mM DL-lactate (50.2 +/- 4.0%). These experiments support the notion that lactate influx into canine skeletal muscle is a function of both a linear (possible diffusive) component and a Michaelis-Menten (carrier-mediated) component.

Animals↗
PubMed1994

Effect of lactate concentration and metabolic rate on net lactate uptake by canine skeletal muscle.

This study addressed two questions: 1) Does net lactate uptake (L) by muscle approach a saturation limit with increasing blood lactate concentration ([La])? 2) Is the muscle net L response to increasing blood [La] affected by metabolic rate (VO2)? The gastrocnemius plantaris muscle group (GP) was isolated in situ in 20 anesthetized dogs. In three series of experiments, a lactate-lactic acid solution was infused into the arterial inflow of the GP to produce five different plasma [La] values: approximately 3, 9, 16, 22, and 30 mM, each of them maintained for 30 min. In one series, the GP remained at rest, whereas in the second series it contracted at 1 Hz and in the third series at 4 Hz. VO2 averaged approximately 3, 43, and 100 ml.kg-1.min-1 at rest and at 1 and 4 Hz, respectively. Within each of the three metabolic rates, increasing plasma [La] resulted in an increase in net L, which was well described (R > 0.98) by exponential equations. These equations predicted net L asymptotic values of 0.80, 0.72, and 1.09 mmol.kg-1.min-1 for rest and for 1 and 4 Hz, respectively. The corresponding plasma [La]s for half-maximal net L from the exponential equations were 16, 10, and 12 mM. Glucose uptake, pyruvate uptake/output, and alanine output by the muscles were not affected by the increasing [La] (and concomitant increases in net L) at any of the metabolic rates. Neither net glycogen synthesis nor depletion was changed by increasing [La].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Subcortical connections of inferior temporal areas TE and TEO in macaque monkeys.

To investigate the subcortical connections of inferior temporal cortex, we injected its anterior and posterior portions (Bonin and Bailey's cytoarchitectonic areas TE and TEO, respectively) in 6 rhesus monkeys with retrograde and anterograde tracers. The results indicate that both areas TE and TEO receive nonreciprocal inputs from several thalamic nuclei, including paracentralis, ventralis anterior, centralis, and limitans, and that TE also receives input from reuniens. Additional nonreciprocal inputs to both areas arise from the hypothalamus, basal nucleus of Meynert, dorsal and median raphe, locus coeruleus, and reticular formation. TE and TEO are reciprocally connected with the lateral, medial, and inferior nuclei of the pulvinar and with the ventral portion of the claustrum. The main subcortical nonreciprocal output from TE and TEO is to the striatum and from TEO to the superior colliculus. TE also sends a very limited projection to nucleus medialis dorsalis magnocellularis of the thalamus. Although the connections of areas TE and TEO are overlapping in most subcortical structures, they are partially segregated in the pulvinar, the reticular nucleus of the thalamus, and the striatum. Specifically, relative to those of TE, the projections of TEO are located more laterally in the medial, lateral, and inferior nuclei of the pulvinar, more ventrally in the reticular nucleus, and more caudally in both the ventral putamen and tail and head of the caudate nucleus.

Animals↗
PubMed1993

Effect of sodium bicarbonate ingestion on exhaustive resistance exercise performance.

Six weight trained males were studied prior to, during, and in recovery from exhaustive resistance exercise, 105 min after ingesting 300 mg.kg-1 of either a placebo or NaHCO3. The exercise test consisted of four sets of 12 repetitions with a fifth set to volitional fatigue on a Universal leg press machine at a resistance equaling approximately 70% of the subjects 1-repetition maximum. Arterialized venous blood was analyzed for lactate concentration, blood gas, and acid-base parameters. The ingestion of NaHCO3 produced a significant increase in resting pH (7.39 to 7.46), HCO3- (22.9 to 28.3 mEq.l-1), and oxygenated base excess (-1.3 to 4.4 mEq.l-1). With the completion of each exercise set, a progressive decline in the acid-base status of both groups was observed (pH set 1-5: NaHCO3, 7.40 to 7.31; placebo, 7.34 to 7.25; HCO3- set 1-5: NaHCO3, 25.3 to 17.9; placebo, 21.7 to 15.3 mEq.l-1; base excess set 1-5: NaHCO3, 3.7 to -7.1; placebo, -1.4 to -10.7 mEq.l-1); however, the NaHCO3 condition was significantly more alkaline than the placebo condition. Blood lactate concentration [La] progressively increased with the completion of each exercise set ([La] set 1-5: NaHCO3, 1.37 to 11.15; placebo, 1.31 to 9.81 mM); but were not significantly different between treatments. Repetitions performed in the final exercise set were not significantly different between groups (NaHCO3: 19.6 +/- 1.6, placebo: 18.2 +/- 1.1 repetitions).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1992

Effect of blood flow on net lactate uptake during steady-level contractions in canine skeletal muscle.

The purpose of this study was to determine the effect of blood flow on net lactate uptake (L) at constant elevated blood lactate concentration and metabolic rate in the in situ dog gastrocnemius-plantaris (GP) muscle. In all experiments, an infusion of lactate/lactic acid at a pH of 3.8 established a blood lactate concentration of 10-13 mM while maintaining normal blood gas/pH status as the GP was stimulated to contract with twitches at 1 Hz. In series 1 (n = 14), blood flow (ml.kg-1.min-1) was controlled by a pump at either 1) the spontaneous level for 1-Hz contractions (control flow = 332 +/- 23) or 2) a level estimated to be approximately 65% greater (high flow = 543 +/- 42). In series 2 (n = 7), perfusion pressure was varied during 1-Hz contractions. Four different perfusion pressures (80, 120, 155, and 180 Torr) were presented to each GP preparation, resulting in mean flow rates of 308 +/- 34, 419 +/- 30, 492 +/- 37, and 646 +/- 30 ml.kg-1.min-1. Increasing blood flow had no significant effect on net L in series 1. Similarly, there was no significant change in net L across the first three perfusion pressures/flow rates in series 2. However, net L (mmol.kg-1.min-1) was significantly increased in the highest perfusion pressure/flow rate period (from 0.335 +/- 0.029 at 80 Torr to 0.431 +/- 0.034 at 180 Torr). This study suggests that blood flow may have an independent effect on net L at the upper extreme of the normal blood flow range during contractions but very little effect over a fairly wide low-to-middle range of flow rates.

Animals↗
PubMed1991

Disruption of developmental timing in the albino rat retina.

We have examined the spatial and temporal gradients of two developmental processes in albino and pigmented rats: outer plexiform layer (OPL) development, and rate of cell production. The OPL first appears as a thin, discontinuous break in the cytoblast layer that is frequently interrupted by the profiles of migrating neuro- and glioblasts. In both strains, this occurs in an area temporal to the optic disc that corresponds to the eventual site of peak ganglion cell density, but is not located along the line of nasotemporal division. The OPL is first evident at P5 in pigmented animals, but its appearance in albino animals is delayed approximately 30 hours, and its development appears to follow a flatter spatial gradient than in pigmented animals. In pigmented animals OPL formation is complete over most of the retina by P10, but in albino animals at this age it is yet to be completely formed at any retinal location. Reductions in mitotic activity are also first evident in temporal retina, but unlike OPL development, appear to follow the same temporal-spatial gradient in both strains. Reductions in temporal retina are obvious by P4, and mitotic activity has ceased altogether in midtemporal retina by P6 and throughout most remaining retinal regions by P8. Thus, the initial reduction of mitotic activity precedes the onset of OPL formation in both strains, but OPL development lags behind the reduction of mitotic activity to a greater extent in albino than in pigmented animals. Some aspects of differentiation within the inner nuclear layer (INL) were also examined. Just prior to the time of the onset of OPL formation, three distinct sublaminae are apparent in the INL. Cells in the innermost sublamina appear to be in an early stage of differentiation. Cells in the middle sublamina appear to be postmigratory, but have not yet begun to differentiate. Cells in the outermost sublamina have the appearance of migrating neuroblasts. At least some of these outer cells appear to migrate across the developing OPL to the outer nuclear layer, since the outermost sublamina becomes thinner and eventually disappears at the same time that the OPL becomes a continuous, uninterrupted plexiform layer. Cells of the middle sublamina apparently begin differentiation at about the time that this migration is complete. Although this sequence is the same in both albino and pigmented strains, its onset is delayed in albino animals by the same amount as the onset of OPL formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Albinism↗
PubMed1991

Lesions of inferior temporal area TE in infant monkeys alter cortico-amygdalar projections.

When inferior temporal area TE is removed bilaterally in infant monkeys, the normally transient projection from area TEO to the lateral basal nucleus of the amygdala is maintained, and the normally limited projection from area TEO to the dorsal part of the lateral nucleus of the amygdala expands to invade the terminal space in the lateral nucleus that is normally occupied by terminals from area TE. The maintenance and sprouting of these projections from area TEO could play a role in the permanent preservation of visual memory ability in monkeys that have received bilateral removal of area TE in infancy.

Aging↗
PubMed1991

Connections of inferior temporal areas TE and TEO with medial temporal-lobe structures in infant and adult 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 connections between inferior temporal cortex and medial temporal-lobe structures in infant and adult monkeys. Inferior temporal cortical areas TEO and TE were injected with WGA conjugated to HRP and tritiated amino acids, respectively, or vice versa, in 1-week-old and 3-4-yr-old Macaca mulatta, and the distributions of labeled cells and terminals were examined in both limbic structures and temporal-lobe cortical areas. In adult monkeys, inferior temporal-limbic connections included projections from area TEO to the dorsal portion of the lateral nucleus of the amygdala and from area TE to the lateral and lateral basal nuclei; inputs to both areas TEO and TE included those from the lateral, lateral basal, and medial basal nuclei of the amygdala and to area TE from the accessory basal nucleus. Additional limbic inputs to both areas TEO and TE arose from the posterior portion of the presubiculum. In infant monkeys, we found, in addition to these adultlike connections, a projection from area TEO to the lateral basal nucleus of the amygdala. Inferior temporal cortical connections in adult monkeys included projections from area TEO to area TE and, in turn, from area TE to area TG and perirhinal area 36, as well as from area TE back to area TEO; inputs to both areas TEO and TE included those from area TG, perirhinal areas 35 and 36, and parahippocampal areas TF and TH. All of these adultlike connections were also observed in infant monkeys, but, in addition, the infants showed projections from area TE to perirhinal area 35 as well as to parahippocampal areas TF and TH, and from area TEO to area TF. Moreover, in infants, the projection from area TE to perirhinal area 36 was considerably more widespread than in adults, both in areal extent and in laminar distribution. The results therefore indicate the existence of projections in infant monkeys from inferior temporal areas to the amygdala, perirhinal cortex, and parahippocampal cortex that are either totally eliminated in adults or more refined in their distribution. Both elimination and refinement of projections thus appear to characterize the maturation of axonal pathways between the inferior temporal cortex and medial temporal-lobe structures in monkeys.

Aging↗
PubMed1988

Abnormal pigmentation and unusual morphogenesis of the optic stalk may be correlated with retinal axon misguidance in embryonic Siamese cats.

Studies of albino rodents have shown that an absence of pigment in the developing optic stalk may alter the position of the first retinal fibers that grow toward the brain, thereby disrupting the gross topographic relationship of fibers in the nerve (Silver and Sapiro: J. Comp. Neurol. 202:521-538, '81). The abnormalities associated with albinism are more extensive in the Siamese cat than-in previously studied species. Therefore, any abnormalities in differentiation of the stalk and axon guidance may be more readily detected. To investigate the guidance and/or misguidance of optic axons, light and electron microscope analyses were made of serial sections through the optic stalk in normally pigmented and Siamese fetal cats. On E20, before axons enter the optic stalk, the only clear morphological distinction between Siamese and normal cats is the distribution of pigment in the stalk. Pigment is found in the dorsal stalk cells of the normal cat for 200 microns from the optic disc. Although the retinal pigment epithelium of the Siamese optic stalk. By E23 axons invade the ventral optic stalk in both strains. Concurrent with the early stages of axonal exit from the retina, there is complete separation of the stalk's dorsal and ventral tiers. As the cleavage occurs, basal lamina invaginates into the zone of separation following along the plane of the old lumen. The ventral stalk fills with axons while the dorsal tier is shed gradually. In contrast, in the Siamese cat, dorsal stalk cells are not sloughed off properly and instead are incorporated ectopically into the nerve. Basal lamina invagination is irregular. Axons do not fill the Siamese stalk symmetrically but enter the region of ectopic cells, which in turn disrupts gross fiber position. Usually, in the mutant, axons originating from the retina temporal to the optic fissure are those that invade the dorsal tier of ectopic cells. The altered position of optic axons in the mutant stalk may provide an explanation for the chiasmatic misrouting of optic axons in this species.

Albinism↗
PubMed1985

The morphology of relay neurons in the dorsal lateral geniculate nucleus of the marsupial brush-tailed possum (Trichosurus vulpecula).

The retinal terminal zones and the morphology of relay neurons within the dorsal lateral geniculate nucleus (LGNd) of the brush-tailed possum (Trichosurus vulpecula) have been investigated with horseradish peroxidase (HRP) tracing techniques. Anterograde transport of HRP from the retina confirmed previous descriptions of the laminar distribution of retinal afferents in this nucleus. In addition, it was found that lamina III consists of two adjacent bands (IIIa and IIIb) of contralateral retinal input, separated by a terminal-free zone 20-40 micron wide. This zone is not apparent with Nissl or fibre stains. Relay neurons in the LGNd were retrogradely filled following cortical injections of HRP, and two classes (A and B) were distinguished. Class A neurons are found in the alpha portion of the LGNd (laminae I, II, III, and IV) and class B neurons in the beta portion (laminae V, VI, and VII). Class A cells are more densely packed and have shorter and more numerous dendrites, less-extensive dendritic arbors, and thicker axons than class B cells. No significant differences were found between the two classes in perikaryal size or thickness of proximal dendrites. Neurons in each lamina of the nucleus have dendritic arbors which ramify extensively within adjacent laminae, except cells in lamina IIIb, which have relatively few dendrites that cross into the cell-free zone and lamina IV.

Animals↗
PubMed1984

Morphology of identified relay cells and interneurons in the dorsal lateral geniculate nucleus of the rat.

The morphology of neurons in the lateral geniculate nucleus of the rat has been examined in both Golgi impregnated and in horseradish peroxidase (HRP) filled material. Two major classes of neurons are seen in Golgi material which encompass the variety of cells described in previous reports. Cells of one group (class A) are routinely labelled by injections of HRP into the visual cortex or optic radiations. This group also displays some morphological variation which may be related to the presence of parallel information channels in the retino-fugal pathway, but clear subgroups cannot be identified on the basis of morphological criteria alone. Cells of the other group (class B) are not labelled by HRP injections into visual cortex or the optic radiations, and are probably local circuit interneurons.

Animals↗
PubMed1979

Postpartum mania in bipolar manic-depressive patients withdrawn from lithium carbonate.

Three women, previously diagnosed as bipolar I manic-depressive, were withdrawn from lithium carbonate prophylaxis immediately prior to their pregnancies. The patients had been euthymic while on lithium carbonate for at least 3 1/2 years prior to their pregnancies. Two of the three patients developed a manic syndrome within 2 weeks postpartum. The use of lithium carbonate during pregnancy, and particularly in the postpartum period, requires reassessment. We advocate an ongoing clinical relationship and the reinstitution of lithium in the third trimester in most cases.

Adult↗
PubMedDate not supplied

Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein.

Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.

Animals↗
PubMedDate not supplied

Connections of inferior temporal areas TEO and TE with parietal and frontal cortex in macaque monkeys.

Inferior temporal cortex is perhaps the highest visual processing area and much anatomical work has focused on its connections with other visual areas in temporal and occipital cortex. Here we report connections of inferior temporal cortex with regions in the frontal and parietal lobes. Inferior temporal areas TEO and TE were injected with WGA-HRP and 3H-AA, respectively, or vice versa, in 1-week-old infant and 3-4-year-old adult monkeys (Macaca mulatta). The results indicated that whereas TEO has more extensive connections with parietal areas, TE has more extensive connections with prefrontal areas. Thus, in the intraparietal sulcus, area TEO is connected with areas LIPd, LIPv, and V3A, and with the as yet undefined region between LIPv and V3A, whereas the connections of TE are predominantly with LIPd, and to a lesser extent with LIPv. In the prefrontal cortex, area TE is connected with areas 8 and 45 in the inferior limb of the anterior bank of the arcuate sulcus, with area 12 on the inferior prefrontal convexity, and with areas 11 and 13 on the orbital surface. By contrast, the connections of area TEO are limited to areas 8, 45, and 12. Furthermore, within prefrontal cortex, the projections from areas TEO and TE terminate in different layers in areas 8 and 45, such that those from TEO terminate in all layers, whereas those from TEO terminate in layers I and V/VI only. In contrast to the connections of areas TEO and TE with various medial temporal-lobe and subcortical structures, which are immature in infant monkeys (Webster et al., 1991, 1993b), the connections with parietal and prefrontal areas appear adult-like as early as 1 week of age.

Aging↗