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Biomedical subjects

E L Smith

Publications and source records attributed to E L Smith.

At least 127 records · Page 7Linked to original sources

Observations on the effects of form deprivation on the refractive status of the monkey.

The consistency of the refractive error alterations produced by monocular form deprivation in developing monkeys and the influence of the duration and the age at the onset of deprivation on the magnitude of these alterations was investigated. Refractive error and axial length measurements are presented for a group of monkeys which had one eye sutured closed for a period exceeding 18 months beginning at various ages ranging from 26 days to 25 months. In addition, we pooled and reanalyzed refractive error and axial length data for monocularly form-deprived monkeys from previous studies. When the alterations in the deprived eye's refractive status are specified with respect to the fellow nondeprived eye, the results are, with a few noteworthy exceptions, consistent between laboratories and individual animals. In most cases, early monocular form deprivation causes the treated eye to develop a longer axial length and to manifest a more myopic/less hyperopic refractive error than the fellow nontreated eye. The magnitude of this deprivation-induced alteration is generally dependent on the duration and the age at the onset of form deprivation. The earlier the deprivation is initiated and the longer it is maintained, the greater the degree of the relative myopia produced in the deprived eye.

Animals↗

Multiple sensitive periods in the development of the primate visual system.

Early in life, abnormal visual experience may disrupt the developmental processes required for the maturation and maintenance of normal visual function. The effects of retinal image deprivation (monocular form deprivation) on four psychophysical functions were investigated in rhesus monkeys to determine if the sensitive period is of the same duration for all types of visual information processing. The basic spectral sensitivity functions of rods and cones have relatively short sensitive periods of development (3 and 6 months) when compared to more complex functions such as monocular spatial vision or resolution (25 months) and binocular vision (greater than 25 months). Therefore, there are multiple, partially overlapping sensitive periods of development and the sensitive period for each specific visual function is probably different.

Age Factors↗

Induction of 5-aminolaevulinate synthase by two- to five-carbon alcohols in cultured chick-embryo hepatocytes. Relationship to induction of cytochrome P-450.

The induction of 5-aminolaevulinate synthase and of cytochrome P-450 by short-chain aliphatic alcohols was compared in primary cultures of chicken-embryo hepatocytes. Isopropyl alcohol, isobutanol, pentan-1-ol and isopentanol alone caused up to a 4-fold increase in 5-aminolaevulinate synthase, whereas ethanol and propan-1-ol did not. Induction of the synthase by isopentanol was maximal at 8 h, and reached a plateau thereafter, whereas the activity induced by 2-propyl-2-isopropylacetamide continued to increase for 20 h. In the presence of 3,4,3',4'-tetrachlorobiphenyl, an inhibitor of haem synthesis at the uroporphyrinogen decarboxylase step, synergistic induction of 5-aminolaevulinate synthase was observed with all the alcohols except ethanol. Ethanol, but not isopentanol, decreased the extent of induction of 5-aminolaevulinate synthase by 2-propyl-2-isopropylacetamide and 3,4,3',4'-tetrachlorobiphenyl (50% decrease at 112 mM-ethanol). Total protein synthesis was not inhibited by ethanol in these cells. The composition of porphyrins was determined after treatment of cells with ethanol, isopentanol or 2-propyl-2-isopropylacetamide. Untreated cells, when incubated with 5-aminolaevulinate for 6 h, accumulated mainly protoporphyrin. However, when cells were pretreated with ethanol, isopentanol or 2-propyl-2-isopropylacetamide for 20 h, and 5-aminolaevulinate was added, 8- and 7-carboxyporphyrins increased, whereas protoporphyrin decreased. The dose responses for induction of either 5-aminolaevulinate synthase or cytochrome P-450 after a 20 h exposure to 3- to 5-carbon alcohols were identical. The results indicate that: simple alcohols can induce both enzymes; hydrophobicity increases their effectiveness; and induction of both enzymes are probably mediated by a common mechanism.

5-Aminolevulinate Synthetase↗

A comparison of the spectral sensitivities of monkeys with anisometropic and stimulus deprivation amblyopia.

Psychophysical procedures were used to determine increment-threshold spectral sensitivity functions for monkeys with either stimulus deprivation amblyopia produced by monocular lid suture or anisometropic amblyopia produced by optical defocus. The spectral sensitivity functions obtained from all of the non-treated control eyes had 3 sensitivity maxima at approximately 445, 520 and 610 nm, and were typical of functions for humans and monkeys with normal trichromatic vision. Relative to their paired control eyes, the amblyopic eyes of all of the lid-sutured monkeys demonstrated reductions in absolute sensitivity. In addition, the amblyopic eyes of the monkeys form-deprived at 1 month of age exhibited alterations in the shapes of their spectral sensitivity functions. The pattern of spectral sensitivity deficits observed in the monkeys form-deprived at 1 month of age varied with the duration of deprivation and indicated that the spectral characteristics of the neural mechanisms mediating stimulus detection in these lid-sutured monkeys' amblyopic and control eyes were substantially different. In contrast, none of the anisometropic amblyopes demonstrated any alterations in the shapes of their spectral sensitivity functions and only one anisometropic subject exhibited a reduction in sensitivity. A comparison of the spectral sensitivity deficits observed in our lid-sutured and anisometropic monkeys reveals that when lid suture and optical defocus are initiated early in life for equivalent periods of time, lid suture produces abnormalities which are both qualitatively and quantitatively different from the abnormalities produced by optical defocus. Therefore, in addition to factors such as the age of onset and the duration of deprivation, it is concluded that the degree of image degradation is important in determining which visual functions are affected and to what extent they are affected.

Amblyopia↗

Relationships between usual nutrient intake and bone-mineral content of women 35-65 years of age: longitudinal and cross-sectional analysis.

In a 4-yr clinical trial, effect on single-photon absorptiometric measurements of arm bones of usual intakes of energy and 14 nutrients plus vitamin-mineral supplements was studied in 99 women, aged 35-65, randomly assigned to placebo (NS) or calcium-supplemented (1.5 g)(S) groups. Cross-sectional analysis of initial bone measurements showed vitamin C (r = 0.313, p less than 0.05) and niacin (r = 0.353, p less than 0.01) correlated with ulna in postmenopausal subjects (n = 67). Longitudinal analysis of bone-change rates of postmenopausal subjects (NS + S) showed higher calcium intakes associated with lower loss rates of humerus bone-mineral content (BMC) (r = 0.360, p less than 0.01). In postmenopausal NS but not S subjects, energy, protein, calcium, phosphorus, zinc, and folate correlate significantly with change in radius BMC; high levels of intake correlated with slower loss (p less than 0.05). Several nutrients besides calcium are related to bone loss in women.

Adult↗

Effect of 1 alpha,25-dihydroxyvitamin D3 on the morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown in serum-free conditions.

The effect of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2-D3] on the proliferation and morphologic and biochemical differentiation of cultured human epidermal keratinocytes grown under defined, serum-free conditions was studied. 1 alpha,25-(OH)2-D3 caused a dose-dependent decrease in proliferation and an increase in the morphologic differentiation of human cultured keratinocytes. The number of attached basal cells decreased when exposed to 1 alpha,25-(OH)2-D3, whereas the number of attached squamous cells, terminally differentiated desquamated cells, and cornified cells increased concurrently. In addition, after incubation with 1 alpha,25-(OH)2-D3, there was a shift to cells of lighter density. In conjunction with its effect on the basal cells, 1 alpha,25-(OH)2-D3 resulted in an inhibition of DNA synthesis. The activity of transglutaminase, the enzyme responsible for cross-linking the proteins of the cornified envelope, was stimulated by 156% with 1 alpha,25-(OH)2-D3, but not with 1 beta,25-(OH)2-D3, a biologically inert isomer. Therefore it appears that 1 alpha,25-(OH)2-D3 is a potent inhibitor of keratinocyte proliferation as well as a stimulator of epidermal terminal differentiation.

Calcitriol↗

Osteoporosis and physical activity.

Bone involution poses serious health risks for aging women. Bone mass is subject to both local (mechanical) and systemic (hormonal) homeostatic control mechanisms. The local forces acting on bone are due to gravity and muscular contraction. There are several theories concerning the mechanisms of local control. When bent, bone functions as a piezoelectric crystal with calcium accumulation on the negatively charged concave surface. Microfractures that occur in response to stress greater than normal levels stimulate osteoclastic activity to remove the damaged structure. Studies of astronauts and immobilized subjects have consistently found bone atrophy. The degree of bone loss is related to the difference in levels of stress normally applied and those at bedrest in the site studied. Correspondingly, athletes have greater bone mass than the sedentary population, with the greatest hypertrophy found in the areas most stressed. Exercise intervention also promotes bone hypertrophy. Both middle-aged and elderly women increase bone mass or reduce the rate of loss in response to physical activity intervention programs.

Adolescent↗

Effects of enucleation of the fixating eye on strabismic amblyopia in monkeys.

The effects of enucleation of the fixating eye on the visual function of the deviating eye were studied in two rhesus monkeys with strabismic amblyopia. An esotropia was surgically induced when the monkeys were approximately 1 mo of age, and the fixating eyes were then enucleated at age 3 yr 11 mo. Four measures of visual function (photopic increment-threshold spectral sensitivity, scotopic spectral sensitivity, spatial modulation sensitivity, and temporal modulation sensitivity) were determined for both eyes prior to enucleation and for the deviating eyes over an 11-month period following the surgical removal of the fixating eye. Both monkeys showed some recovery of contrast sensitivity of their deviating eyes. The extrapolated cut-off values for their spatial modulation sensitivity functions increased from .27 to 2.8 c/deg for one animal and from .28 to 6.3 c/deg for the other. The extrapolated cut-off frequencies for the temporal modulation sensitivity functions of both animals showed an increase of 20-25 Hz compared to the pre-enucleation values. The spectral sensitivity functions of one monkey recovered to near normal values following enucleation, while both the photopic and scotopic functions of the other animal remained at pre-enucleation levels. Overall, the results of the experiments indicate that the removal of the fixating eyes of monkeys with strabismic amblyopia can result in significant improvements in the functional capacity of their deviating eyes.

Amblyopia↗

The critical period for corpus callosum section to affect cortical binocularity.

The period of time during which surgical section of the corpus callosum (CC) is effective in altering the physiological properties of cells in cat striate cortex was investigated. Cats which had the CC transected between 13 days and 24 weeks of age were studied using extracellular, single-unit recording procedures. Analysis of the results from 1,747 cortical units indicate that when the CC was sectioned prior to 19 days of age there was a reduction in the encounter rate of binocularly activated neurons and an increase in the proportion of neurons dominated by the contralateral eye. The decrease in cortical binocularity was observed in both simple and complex cell populations, and at all receptive field eccentricities studied (0-39 degrees). However, when the CC was sectioned after 19 postnatal days, no physiological changes were detected. Thus, in contrast with previous studies (Payne et al. 1980a, b) no changes were found following CC section in adult cats. The results therefore define a critical period which ends before 3 weeks of age during which corpus callosum section reduces striate cortex binocularity. Although the corpus callosum critical period is much shorter than the critical period for experiential alterations in cortical binocularity, the physiologically determined limits of the callosal critical period agree with the behaviorally determined limits previously found for the callosal critical period (Elberger 1984).

Animals↗

Effects on blood pressure of calcium supplementation of women.

The relationship between dietary and supplemental (1.5 g/d) calcium intake and blood pressure was examined in 81 normotensive and 34 medicated hypertensive women between the ages of 35 and 65 years who completed a 4-yr clinical trial to assess age-associated bone loss in women. Calcium intakes were monitored during the entire study. Resting blood pressures and systolic blood pressure response (SBPR) to a stress test were recorded three times during the study. At the end of the study there was no relationship between systolic or diastolic blood pressure or SBPR and total calcium intake in normotensive women (n = 81). In the medicated hypertensive group (n = 34) there was a 13 mm Hg decrease in systolic pressure of supplemented women (n = 18) and a 7 mm Hg increase in unsupplemented women (n = 16) over the 4 yr (p less than .02).

Adult↗

Effects of intraindividual and interindividual variation in repeated dietary records.

In this study 5,115 daily diet records were collected from 151 women on two randomly selected days per sampling month (29 days) over a two-year period. Yearly estimates of the ratios of intraindividual (sigma w2) and interindividual (sigma b2) variance components were calculated for dietary intake of 15 nutrients and for dietary intake + vitamin/mineral supplements. From one year to the next, corresponding ratios of sigma w2/sigma b2 were nearly identical. Intraindividual variation in dietary intake of all 15 nutrients was greater than interindividual variation (sigma w2/sigma b2 greater than 1). Variance component ratios for highly supplemented nutrients such as iron, vitamin C and B vitamins were less than one (sigma w2/sigma b2 less than 1). Using the ratios of sigma w2/sigma b2, it was calculated that between six and 99 repeated records measuring dietary intake and between two and 31 records measuring total intake may be needed per individual to ensure that the estimate of the population correlation (rho DF) between an individual's "usual" dietary intake or total intake of a dietary risk factor and an individual's mean or usual level of a physiologic risk factor was within 10% of the true population correlation coefficient (rho xy). It was also found that twice as many dietary records per individual were required to estimate the population slope (beta xy) within 10%. These results have serious implications for the design and analysis of prospective nutritional studies.

Adult↗

Binocular summation in man and monkey.

Binocular summation, using spatial and temporal modulation sensitivity measurements, has been investigated for human and rhesus monkey observers. In experiments where the refractive errors of both eyes were optimally corrected, the binocular summation functions for both species were similar in magnitude and form, and showed higher summation ratios for temporally modulated stimuli than for spatially modulated stimuli. Monocular retinal image defocus produced a reduction in binocular summation for spatial gratings with the amount of reduction dependent on both the amount of relative defocus and the spatial frequency of the stimulus grating. In contrast, monocular defocus did not effect the magnitude of binocular summation for spatial gratings with the amount for any of the conditions investigated. Over-all, the results of these investigations indicate that binocular summation measures of binocular function may have some advantages over other tests of binocular function that could be utilized in the clinical examination of patients.

Adult↗

Rhesus monkey as a model for normal vision of humans.

Data for three fundamental psychophysical functions (spatial modulation sensitivity, temporal modulation sensitivity, and increment-threshold spectral sensitivity) were compared for groups of 12 rhesus monkeys and 12 human subjects. It was found that there are important, nontrivial differences between the data for monkeys and humans, but that many of the differences could be accounted for by structural or passive differences in the visual systems. Therefore, it was concluded that the neural processing of information along the visual pathways of the two species is generally similar and that the monkey is an excellent model of the human visual system.

Animals↗

Effects of chronic exercise during aging on muscle and end-plate morphology in rats.

Terminal sprouting, myofiber atrophy, and fiber type changes were studied in soleus and distal gastrocnemius muscles of 21- and 26-mo-old rats and in rats who performed treadmill running from 21 to 26 mo. End-plate structure and muscle fiber types were demonstrated by staining for acetylcholinesterase and myosin ATPase activity. Terminal sprouting was expressed as the percentage of end plates with growth configurations. Fiber atrophy was assessed as percentage of small-diameter fibers. In all three groups, the percentage of small-diameter fibers was significantly smaller and the percentage of growth configurations significantly larger in the soleus than in the gastrocnemius. The exercised-soleus group had a significantly higher percentage of growth configurations than the 26-mo controls, which had a higher percentage than the 21-mo controls. Percentages among gastrocnemius groups were not different. Fiber type was similar among gastrocnemius groups. However, the exercised-soleus had significantly more slow-twitch fibers than the controls. These data suggest that the soleus responds differently to chronic exercise during aging than does the gastrocnemius.

Aging↗

Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions.

Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography (HPLC) with electrochemical detection of endogenous dopamine content and by [3H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [3H]dopamine uptake compared with that of their matched controls. Normal appearing [3H]GABA and [3H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry. When functioning normally, the dopaminergic AC of the cat's retina appears to make the receptive field of the off-center cell more sustained and may make its spatial summation characteristics more linear while adjusting the intensitive properties of neurons in both the on- and off-center pathways.

Animals↗

The relationship between binocular rivalry and strabismic suppression.

Increment-threshold spectral sensitivity functions were determined for normal observers during binocular rivalry and for esotropic observers during strabismic suppression and under viewing conditions that normally induce binocular rivalry. Depending on the spatial and temporal properties of the test stimulus, the normal observers exhibited a wavelength-specific loss in sensitivity during the suppression phase of rivalry, which suggests that binocular rivalry differentially attenuates the sensitivity of the chromatic mechanisms relative to the luminance mechanisms. In contrast, regardless of the test stimulus dimensions, the esotropic observers did not manifest a wavelength-specific loss in sensitivity either during strabismic suppression or under conditions that normally induce binocular rivalry. The different patterns of suppression shown by the normal and esotropic subjects suggest that strabismic observers do not demonstrate normal binocular rivalry, and that strabismic suppression and normal binocular rivalry suppression are mediated by different neural mechanisms.

Adult↗