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Biomedical subjects

E L Smith

Publications and source records attributed to E L Smith.

At least 19 recordsLinked to original sources
PubMed1992

2-Amino-3,4-dimethylimidazo[4,5-f]quinoline induces and inhibits cytochrome P450 from the IA subfamily in chick and rat hepatocytes.

Several heterocyclic amines, found in cooked food, are powerful mutagens in the Ames Salmonella mutagenicity test system. One of these, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is one of the most mutagenic chemicals tested in this assay. In primary cultures of chick and rat hepatocytes, MeIQ, by itself, induced cytochrome P450 from the IA subfamily but was a weak inducer compared to 3-methylcholanthrene. However, in both chick and rat hepatocytes in culture, MeIQ decreased the amount of 3-methylcholanthrene-induced ethoxyresorufin deethylase activity, which is catalyzed by cytochrome P450 IA. The protein moiety of cytochrome P450 IA was decreased at MeIQ concentrations of 2.5 micrograms/ml or greater in chick hepatocytes and 25 micrograms/ml in rat hepatocytes. In hepatic microsomes from methylcholanthrene-treated chicks and rats, MeIQ was a competitive inhibitor of both ethoxyresorufin deethylase activity, a reaction catalyzed mainly by rodent cytochrome P450 IA1, and uroporphyrinogen oxidation, a reaction catalyzed by rodent P450 IA2. In cultured chick hepatocytes, MeIQ also decreased cytochrome P450-mediated oxidation of uroporphyrinogen by intact cells. The ability of MeIQ to inhibit as well as to induce cytochrome P450s of the IA subfamily may be important in assessing the mutagenic and carcinogenic effects of MeIQ in mammals.

Animals↗
PubMed1992

Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina.

The retinotopic map in the visual cortex of adult mammals can reorganize in response to a small injury in a restricted region of retina. Although the mechanisms underlying this neural plasticity in adults are not well understood, it is possible that rapid, adaptive alterations in the effectiveness of existing connections play a key role in the reorganization of cortical topography following peripheral deafferentation. In order to test this hypothesis, a small retinal lesion was made in one eye of adult cats and the visual cortex was mapped before and immediately after enucleating the non-lesioned eye. We found that substantial reorganization takes place within hours of enucleation.

Animals↗
PubMed1992

Effects of interocular suppression on spectral sensitivity.

A stable form of interocular suppression, referred to as "permanent suppression," can be produced by presenting a contoured field to one eye and a spatially homogenous field to the fellow eye, a viewing condition analogous to the classic "hole-in-the-hand" illusion. We examined the relation between permanent suppression and binocular rivalry suppression by comparing the changes in the increment-threshold spectral sensitivity function produced by these two forms of suppression. Permanent suppression produced a reduction in spectral sensitivity; however, in contrast to binocular rivalry suppression, the sensitivity alterations associated with permanent suppression were independent of the test-probe wavelength. The different patterns of sensitivity loss observed during binocular rivalry and permanent suppression indicate that different neural mechanisms mediate these two forms of interocular suppression.

Humans↗
PubMed1992

Prior binocular dissociation reduces monocular form deprivation amblyopia in monkeys.

The profound visual deficits associated with early monocular form deprivation (MD) are caused largely by competitive binocular interactions in the visual cortex. We tested the hypothesis that disrupting normal cortical binocularity prior to the onset of MD would reduce the degree of form deprivation amblyopia compared to that produced in animals that had normal binocular vision prior to MD. An optical strabismus was maintained in two rhesus monkeys between 30 and 90 d old, a rearing strategy that substantially reduces excitatory cortical binocular interactions. Subsequently, the lids of one eye were sutured closed for 9 mo. Comparison data were obtained from a series of form-deprived monkeys reared in a normal manner prior to the onset of MD. Psychophysical procedures were employed to measure the effects of the rearing procedures on the spatial contrast sensitivity functions for each eye. By itself, MD resulted in a severe amblyopia. The spatial resolution of the deprived eyes of monkeys lid sutured by 5 mo of age was about 6 octaves lower than normal values (Snellen acuities of about 20/2000). In contrast, equivalent periods of MD had a much smaller effect on the spatial vision of the prism-reared monkeys. In both cases, the deprived-eye cut-off spatial frequencies were within 1 octave of the nondeprived-eye values and were comparable to cut-offs for binocularly form-deprived monkeys. The results demonstrate that prior binocular image dissociation protects young monkeys from the effects of MD, probably by reducing the potential for antagonistic, competitive binocular interactions in the visual cortex.

Amblyopia↗
PubMed1991

Ethanol increases cytochromes P450IIE, IIB1/2, and IIIA in cultured rat hepatocytes.

In intact rats, ethanol treatment has been associated with increases in hepatic levels of both P450IIB1/2 and P450IIE. When rat hepatocytes were cultured on an extracellular tumor matrix (Matrigel), exposure to ethanol from 48 to 96 h in culture resulted in increases in cytochromes P450IIE, IIB1/2, and IIIA. Cytochrome P450IIE was detected immunologically and enzymatically, using two activities associated with cytochrome P450IIE, p-nitrophenol hydroxylation, and acetaminophen activation to a metabolite that binds to glutathione. The content of cytochrome P450IIE in freshly isolated cells decreased when the cells were placed in culture. Exposure of the cultured hepatocytes to ethanol from 48 to 96 h after inoculation resulted in an increase in cytochrome P450IIE compared to untreated cultured cells. In addition, in culture, the amount of enzymatically active protein after ethanol treatment was equal to that in hepatocytes freshly isolated from intact animals. Ethanol treatment resulted in increases in cytochrome P450IIB1/2 compared to untreated cells, as shown immunologically and by increased benzyloxyresorufin dealkylase activity. However, phenobarbital induced cytochrome P450IIB1/2 to higher levels, compared to ethanol. Ethanol and phenobarbital treatments both increased P450IIIA, as determined immunologically and by the amount of propoxycoumarin depropylase activity that is inhibited by triacetyloleandomycin. However, the amount of P450IIIA increased after ethanol treatment was less than that increased after treatment with dexamethasone in these cells. The ethanol-mediated increases in all four forms of cytochrome P450 in culture suggest that these increases in the intact animal result from direct effects of ethanol on the liver.

Acetaminophen↗
PubMed1991

A histomorphometric study of cortical bone activity during increased weight-bearing exercise.

To quantify cortical bone response to weight-bearing exercise, bone size, mineral content, and formation were measured at the femoral midshaft in swine. Bone formation was measured histomorphometrically on the periosteal, endosteal, and osteonal surfaces. Sedentary adult crossbred sows (3 years, 229 kg) were randomly assigned to basal (B, n = 6), control (C, n = 7), or trained (T, n = 7) groups. The basal and control groups did not exercise and were killed initially (B) or after 20 weeks (C). The trained group walked on a treadmill 20 minutes/day at 5 km/h and 5% grade, 5 days/week for 20 weeks. Bone length, area, or fat-free dry weight was not different with time (B versus C) or with training (C versus T). Periosteal modeling was stimulated by walking. Periosteal formation surface and mineral apposition rate (MAR) were greater in trained than control femora. No effects of walking were measured on the endosteal surface. Intracortical remodeling was not affected by walking. The number of labeled osteons (22.4 cm-2) was not different among groups, but osteonal MAR was greater in trained (1.18 microns/day) than control (0.96 mu/day) femora. Walking for 20 weeks in the previously sedentary sows was not a sufficient stimulus to create differences in gross measures of bone size or mineral content but did increase periosteal and intracortical MAR. The primary effect of increased exercise appeared to be osteoblast activation.

Animals↗
PubMed1991

Physical activity effects on bone metabolism.

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

Adolescent↗
PubMed1991

Refractive-error changes in kitten eyes produced by chronic on-channel blockade.

The dependence of the emmetropization process on retinal ON-channel activity was examined in developing kittens by making regular intravitreal injections of D,L-2-amino-4-phosphonobutyric acid (APB). In comparison to sham-injected control eyes, the APB-treated eyes had shorter axial lengths and were more hyperopic. Since chronic atropinization did not alter the development of the APB-induced hyperopia, these anomalous refractive errors are not the result of altered accommodative function. The axial hyperopia observed in the APB-treated eyes indicates that the mechanisms responsible for normal axial elongation are dependent to some extent on ON-channel activity and that, even in the presence of a clear retinal image, OFF-channel activity, by itself, is not sufficient to regulate the normal emmetropization process.

Aminobutyrates↗
PubMed1991

Disruption of binocularly correlated signals alters the postnatal development of spatial properties in cat striate cortical neurons.

1. Extracellular single-cell recording techniques were employed to investigate the effects of ocular misalignment on the postnatal development of the spatial response properties of striate cortical neurons. The primary objective of the study was to gain insight into the neural basis of strabismic amblyopia. 2. Two basic rearing strategies were used to study specific aspects of experimental strabismus in developing kittens. In one group, strabismus was optically induced by fitting kittens with goggles that held a 15-diopter base-in prism in front of one eye (MP) or both eyes (BP) between the ages of 4 wk and 4 mo. In the second group, a unilateral esotropia was surgically induced at 3 wks of age either by the simple resection of the lateral rectus muscle tendon (tenotomy) or by a more drastic procedure that involved removing sections of the lateral rectus and superior oblique muscles (myectomy). In addition, the eyelids of the nondeviating eyes of these kittens were sutured closed (ESO/MD). The first rearing paradigm isolated the effects of conflicting visual inputs on neural development, whereas the second procedure isolated the effects of anomalous ocular motility by producing a misalignment without putting the deviated eye at a competitive disadvantage. 3. The recording experiments were conducted when the animals were greater than or equal to 9 mo of age. A total of 445 striate cortical neurons were isolated and quantitatively studied in 17 cats (3 MPs, 3 BPs, 5 ESO/MDs, 3 goggle-reared controls, and 3 normals). In addition, we analyzed the distribution of preferred stimulus orientations of 1,205 single units that had been studied qualitatively in our previous investigation of 42 kittens reared with optically induced strabismus. 4. As expected, the proportion of binocularly driven units was reduced in both MP and BP cats. The great majority of units in ESO/MD animals were exclusively driven or highly dominated by the open deviating eye. 5. Prism-reared animals showed physiological deficits in spatial resolution, contrast sensitivity, contrast gain, and peak firing rate. These effects were manifest in both eyes, although there was always an interocular asymmetry in the deficits observed in the two eyes. In MP animals, the units dominated by the treated eye, which was contralateral to the recording hemisphere, were on the average more severely affected. The interocular asymmetry was smaller in BP cats; however, two of the three BP animals also showed a greater deficit in those units dominated by the contralateral eye.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effect of training on VO2max, thigh strength, and muscle morphology in septuagenarian women.

The purpose of this study was to determine the effects of a long-term (50 wk) combined aerobic-resistance training program on maximal oxygen consumption (VO2max, thigh strength, and vastus lateralis fiber morphology in healthy septuagenarian women (mean age = 72 +/- 6 yr). Subjects volunteered to be in either an exercise (Ex; N = 17) or control (Con; N = 10) group. Con subjects were 34% less active in winter than in summer, Ex subjects maintained their summer activity level on exercise days in winter. Initial, intermediate (20 wk), and final (50 wk) measurements were made for isokinetic knee extension/flexion strength; VO2max and morphological measurements from a muscle biopsy were made at the initial and final times only. Both groups gained in leg strength (Ex = +6.5%; Con = +7.8%; P less than or equal to 0.05) during the summer; in the winter the Ex group maintained leg strength and the Con group declined 12.2% (P less than or equal to 0.05). The fast-twitch muscle fiber area (Type IIb) increased 29% (P less than or equal to 0.001) in the Ex group and declined 26% (P = 0.014) in the Con group. VO2max increased only in the Ex group (16%; P less than 0.001). We conclude that healthy septuagenarian women can increase aerobic capacity, leg strength, and Type IIb muscle fiber area with a long-duration, combined aerobic-resistance exercise program.

Aged↗
PubMed1991

Binocular beat VEPs: losses of cortical binocularity in monkeys reared with abnormal visual experience.

Binocular beat VEPs were recorded from anesthetized macaque monkeys with diverse visual rearing histories, including surgically induced esotropia, optical prism dissociation, optical anisometropia, monocular form deprivation (MD), and normal rearing. Dichoptic visual stimulation was produced by temporally modulating the luminances of uniform fields presented to each eye. Five pairs of temporal frequencies were used, all of which had interocular differences of 2 Hz. While normally reared animals exhibited robust binocular beat responses strongly tuned to temporal frequency, the responses from monkeys with abnormal rearing experiences showed losses in beat signal-to-noise ratios that correlated with the age of onset or duration of the abnormal visual experience. Surgical esotropia induced early in life (2 months of age) produced a virtually complete loss of the binocular beat response; the cortical losses were less severe as the age of surgery rose to 10 months. Monkeys reared with either anisometropia or optical dissociation also manifested substantial reductions in evoked beat nonlinearity. MD monkeys sutured relatively late in development (8 and 25 months) showed mild reductions. The correspondence of these results to earlier psychophysical data obtained from these animals, and the similarity of these results to previous findings with binocularly normal and abnormal humans, supports the use of the binocular beat as an objective, noninvasive index of binocular neural integrity.

Amblyopia↗
PubMed1991

Muscular strength and bone density with weight training in middle-aged women.

Previous research has demonstrated positive correlations between bone mass and both physical activity and muscular strength. There is a paucity of information describing the specific type of exercise which most benefits the human skeleton. The effects of a 1 yr weight training program on 18 middle-aged women participating in an endurance dance program (E + W) compared with 17 other women in the endurance dance program only (E) and with 19 sedentary controls (C) were studied by measuring muscular strength and bone mineral density (BMD). Eighteen women in the E + W group demonstrated increases in all strength measurements, whereas the E and C groups either had smaller increases or had declined. A significant group x test interaction term, indicating that groups responded differently over time, was observed for nondominant isokinetic elbow flexion measured through the range of motion at a constant velocity of 60 degrees.s-1 (P less than 0.05), nondominant isokinetic elbow extension at 180 degrees.s-1 (P less than 0.01), and nondominant isokinetic elbow flexion at 180 degrees.s-1 (P less than 0.05). BMD did not change significantly except that a significant group x test interaction term appeared for the radius ultradistal site (P less than 0.01). BMD of the humerus and femoral Ward's triangle increased nonsignificantly in both E and E + W over the year. This weight training program increased muscular strength but did not increase measured bone mass.

Adult↗
PubMed1991

Functional effects of bilateral form deprivation in monkeys.

Psychophysical methods were used to study the effects of binocular form deprivation, initiated at 1 month of age, on the visual sensitivities of young monkeys. All the monkeys reared with bilateral form deprivation for 7 weeks or longer had reduced spatial contrast sensitivity for both eyes. Although the contrast sensitivity deficits of the bilaterally form-deprived monkeys generally were larger for one eye than the other, the magnitudes of the deficits were small compared with those produced by similar periods of unilateral form deprivation. For other monocular vision functions investigated, temporal contrast sensitivity and increment-threshold spectral sensitivity, the data for the bilaterally form-deprived animals showed only minor variations from those of the control monkeys. However, none of the bilaterally form-deprived monkeys had binocular vision on either measures of binocular summation or stereodetection, even if the animal had normal monocular vision functions. Therefore, these results show that monocular sensory deficits caused by abnormal early visual experience as a result of bilateral form deprivation are much less severe than those caused by unilateral form deprivation. The differences in the severity of visual deficits may be attributed to the consequences of anomalous binocular competition associated with unilateral form deprivation that was minimized during bilateral form deprivation. Thus, these results illustrate that anomalous binocular competition is more detrimental to the developing visual system of infants than direct deprivation per se.

Amblyopia↗
PubMed1991

Bilateral form deprivation in monkeys. Electrophysiologic and anatomic consequences.

The response characteristics of neurons in the striate cortex are described for rhesus monkeys that underwent bilateral form deprivation by surgical closure of the eyelids starting within the first month of life and lasting for 2, 6, 7, 13, or 16 weeks. The monkeys had been tested for visual deficits resulting from these experimental deprivations. Single-unit recordings from the striate cortices of these animals showed a single significant abnormality; the absence of excitatory binocular input. Whereas, 76% of the neurons in the foveal striate cortex of the normal animals were binocular, fewer than 20% of the neurons in the experimental monkeys were binocular. However, each eye was well represented by monocular cells. As demonstrated in oblique microelectrode penetrations, the cortical eye-dominance zones for each eye appeared to be of equal width with sharp transitions at the monocular boundaries. The sizes of the cells of the lateral geniculate nuclei were smaller (-15%) than those in controls. Binocular form deprivation early in life has its most obvious effect on the physiology and function of cortical binocular neurons and secondarily on the size of neurons of the lateral geniculate nucleus.

Animals↗
PubMed1990

Behavioral studies of the sensitive periods of development of visual functions in monkeys.

The age-dependent effects of monocular form deprivation on psychophysically determined visual functions were investigated in rhesus monkeys. Monocular form deprivation was initiated at various ages from 1 to 25 months and maintained for 18 months. The effects of form deprivation varied across the visual functions evaluated. Absolute scotopic sensitivity was depressed by form deprivation initiated only at 1 or 2 months of age. Photopic, increment-threshold spectral sensitivity functions showed alterations in sensitivity levels for monkeys treated at 5 months of age or earlier, with no effect thereafter. Monocular form deprivation at 1 to 5 months of age resulted in profound deficits in spatial modulation sensitivity. The effects on spatial vision decreased systematically as the age of onset was delayed from age 6 to 18 months. Finally, binocular summation measures revealed an absence of binocular vision even for the monkey form-deprived at 25 months of age, i.e. the experimental treatment series failed to define the upper limit of the age-range for the effects of monocular form deprivation on binocular summation mechanisms. Comparisons of the age-dependent effects of monocular form deprivation across the various functions demonstrated that the sensitive period, i.e. the period of life during which a visual function may be altered by monocular form deprivation, was different for each of the psychophysical measures of visual function.

Animals↗
PubMed1990

Spatio-temporal interactions and the spatial phase preferences of visual neurons.

We recorded single neuron responses in the cat's lateral geniculate nucleus (LGN) and visual cortex to compound stimuli composed of two sinusoidal gratings in a 2:1 frequency ratio. To probe visual receptive field symmetry, we varied the relative spatial phase of the two components and measured the effect on neuronal responses. We expected that on-center LGN neurons would respond best to gratings combined in positive cosine (bright bar) phase, while off-center LGN neurons would respond best to gratings combined in negative cosine (dark bar) phase. When drifting stimuli were used, cells' phase preferences were roughly 90 deg away from the expected values; when stationary, contrast-modulated stimuli were used, phase preferences were as originally predicted. Computer simulations showed that this discrepancy could be explained by taking into account the cells' temporal properties. Thus, tests using drifting stimuli confound the spatial structure of visual neural receptive fields with their temporal response characteristics. A small sample of data from cortical neurons reveals the same confound.

Action Potentials↗
PubMed1990

Hepatic alcohol dehydrogenase activity in chick hepatocytes towards the major alcohols present in commercial alcoholic beverages: comparison with activities in rat and human liver.

We have compared hepatic alcohol dehydrogenase activities in chick, rat and human liver with the major alcohols in commercial alcoholic beverages. 1. Chick and rat hepatic alcohol dehydrogenase was greater when assayed at a physiological pH in buffer containing chloride ions, as compared with the activity in pyrophosphate buffer at alkaline pH. 2. In contrast to reports of instability of ADH to freezing, we found the enzyme from all three species stable to freezing in 0.25 M sucrose. 3. Rat liver enzymatic activity was unstable in the presence of substrate, where as that of chick and human was not. 4. For all three species, the Km of hepatic ADH for substrate decreased with increasing chain length of alcohols. In both chick and human samples, the Vmax values for the higher chain alcohols were similar to that with ethanol, while in rat samples, ADH activity was dramatically lower with the higher chain alcohols compared to ethanol.

1-Propanol↗