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Biomedical subjects

A B Fulton

Publications and source records attributed to A B Fulton.

At least 19 recordsLinked to original sources

Association of titin and myosin heavy chain in developing skeletal muscle.

To understand molecular interactions that organize developing myofibrils, we examined the biosynthesis and interaction of titin and myosin heavy chain in cultures of developing muscle. Use of pulse-labeling, immunoprecipitation, and a reversible cross-linking procedure demonstrates that within minutes of synthesis, titin and myosin heavy chain can be chemically cross-linked into very large, detergent-resistant complexes retaining many features of intact myotubes. These complexes, predominantly of titin and myosin, occur very early in myofibrillogenesis as well as later. These data suggest that synthesis and assembly of titin and myosin are temporally and spatially coordinated in nascent myofibrils and support the hypothesis that titin molecules help to organize sarcomere formation.

Animals

The effect of light adaptation on scotopic spatial summation in 10-week-old infants.

Psychophysical area-intensity functions of individual 10-week-old human infants and adults were obtained in the dark adapted state, and in the presence of a steady background that elevated threshold 1 log unit above the dark adapted level. For dark adapted infants, the mean diameter for complete spatial summation (4.42 degrees; SD: 1.67 degrees) was significantly larger than that of adults (2.32 degrees; SD: 0.09 degrees). The background reduced the mean critical diameter to 2.67 degrees for infants (SD: 0.64 degrees) and to 1.16 degrees for adults (SD: 0.08 degrees). Spatial probability summation has similar effects on infant and adult thresholds, and, therefore, does not appear to account for the developmental decrease in critical diameters. Rather, decreases in receptive field size are suspected.

Adaptation, Ocular

Effects of halothane on children's electroretinograms.

BACKGROUND: At times, anesthesia is necessary to test children's electroretinographic (ERG) responses. Halothane, an anesthetic commonly used for pediatric patients, affects some aspects of ERG responses, but it is unknown if halothane affects ERG parameters evaluated by contemporary clinical protocols. METHODS: Scotopic and photopic ERG responses were recorded from children when awake and then under halothane. RESULTS: Halothane has no effect on scotopic b-wave stimulus/response parameters, including amplitude, sensitivity, and implicit time. Scotopic a-wave amplitudes, implicit times, model parameters, and ratio of a- to b-wave amplitudes are unaffected by halothane. The amplitudes and implicit times of photopic responses to red flashes and 30 Hz flickering white light are not altered by halothane. Halothane causes no significant change in amplitudes and implicit times of the oscillatory potential wavelets. CONCLUSION: These results suggest that significant departures of ERG responses (studied with the protocol described herein) from a laboratory's normal values cannot be attributed to halothane.

Adolescent

The rod sensitivity of dark adapted human infants.

The determinants of infants' low scotopic visual sensitivity are controversial. Some interpret infants' scotopic vision as indicative of immature rod photoreceptor function while others attribute infantile sensitivities mainly to post receptoral immaturities. To date the rod photoreceptor sensitivity of human infants has not actually been measured. In the work reported herein, electroretinographic a-wave responses, which represent the rod photoresponse, were recorded from dark adapted 10-week old infants and adult control subjects. Rod isolated a-waves indicate that 10-week-old infants' rods are less sensitive than adults'. Thus, any explanation of infants' scotopic visual sensitivity must take into account this fundamental property of infants' rods, low sensitivity.

Adult

Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis.

Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. In the mature myofibril, titin molecules span from M line to Z line, forming a third filament system which provides sarcomeric alignment and elastic recoil. In the developing sarcomere, accumulating evidence from studies both in vivo and in vitro implicates titin as part of a morphogenetic scaffolding, upon which critical events in myofibrillogenesis are coordinated in a time- and space-dependent manner.

Animals

Dark adapted thresholds in young RCS rats.

The dark adapted thresholds of black-eyed RCS rats and cogenic controls were measured using a new psychophysical procedure that permits determination of thresholds at earlier ages than previously possible. Rats were tested longitudinally between about ages 1 and 3 months. At all ages, thresholds of RCS rats were higher than those of controls. Thresholds did not change systematically with age for either RCS rats or controls. At age 3 months, when the RCS rats' b-wave is no longer recordable, RCS thresholds are about 2.2 log units higher than those of controls.

Aging

Temporal summation in dark-adapted 10-week old infants.

The effect of stimulus duration on the b-wave and psychophysical responses of dark-adapted 10-week-old infants and adult control subjects is reported. Both infant and adult b-wave sensitivities vary with stimulus duration, show summation for brief duration stimuli, critical durations estimated at 88-155 msec, and little variation in sensitivity for longer durations. There are however, substantial differences between the infant and adult psychophysical temporal summation functions. The infant function is described by a straight line, slope about -0.5, across all flash durations while adults show summation at durations less than 100 msec and critical durations of 136 to 151 msec. Adult, but not infant, b-wave integration times and b-wave rise and fall times show duration-dependent changes. Thus, both ERG and psychophysical measures demonstrate immaturities in the rod mediated function of the infant retina.

Adult

Electroretinographic assessment of background adaptation in 10-week-old human infants.

Full field, scotopic b-wave stimulus/response functions of 10-week-old infants and adults were measured in the dark-adapted condition, and in the presence of steady backgrounds. Dark adapted b-wave sensitivity (log sigma) differed significantly between infants and adults; the median dark adapted sensitivity of infants was 0.50 log unit less than that of adults. The median eigengraus of infants (-1.32 log scot. td) and adults (-1.55 log scot. td) did not differ significantly. The median slope of the linear portion of the background adaptation function was about 0.9 for infants and adults. These results argue for post-receptoral immaturities, but do not rule out receptoral immaturities.

Adaptation, Ocular

Visual development of infants with severe ocular disorders.

Among 11 patients who presented as blind in early infancy, with Leber's congenital amaurosis (5 patients), optic nerve hypoplasia (4 patients), or macular colobomata (2 patients), 8 developed visually guided behavior and measurable grating acuity by age 5 to 46 months. All children with measurable grating acuity demonstrated visually guided mobility. Grating acuity was predictive of later visual performance in 10 of 11 patients by age 12 to 16 months. The best grating acuity attained by 7 months was 1.3 to 3.0 cycles/degrees (20/460 to 20/200) and 0.13 cycles/degrees (20/4700) by month 8. Two patients with Leber's congenital amaurosis and one with optic nerve hypoplasia remained blind. No clinical features existed to differentiate these three patients from the eight whose visual status improved. Posterior visual pathway maturation may underlie the improvement.

Child

The quantity of rhodopsin in young human eyes.

The rhodopsin content of 20 eyes of infants and children ages 27 weeks gestation to 8 years (11 donors) was assayed and compared to the rhodopsin content of adults (36 eyes; 19 donors). Infants have significantly lower rhodopsin contents than adults. On average the rhodopsin content of young infants is about a third of adults. Previously reported full-field b-wave sensitivity of young infants is about 0.5 log units, that is about a third, less than adults. Thus, as previously found in infant rats, photon capture by rhodopsin appears to limit the dark adapted sensitivity of young human infants.

Adolescent

Hyperopia in complicated Leber's congenital amaurosis.

We studied the refractive status of 13 children with Leber's congenital amaurosis. Seven had the disease complicated by neurological or other systemic abnormalities, while the other 6 patients had only ophthalmic abnormalities. All 13 patients were hyperopic. The magnitude of hyperopia did not differ significantly between the complicated and uncomplicated groups. Therefore, one cannot, as previously suggested, use the presence of high hyperopia to differentiate an uncomplicated form of Leber's congenital amaurosis from one complicated by neurologic or other systemic abnormalities. The concurrence of hyperopia with Leber's congenital amaurosis should not steer the physician away from careful neurologic systemic or biochemical evaluation of the child.

Age Factors

The quantity of rhodopsin in human eyes.

The content of rhodopsin in the eyes of 15 donors (30 eyes) was determined. Both retinal and pigment epithelial fractions were collected from each globe, extracted using 1% CTAB, and the rhodopsin difference spectrum of each fraction was obtained separately. The total amount of rhodopsin, obtained by summing the amounts recovered from the retinal and PE fractions, ranged from 2.00 to 11.94 (median: 6.40) nmoles/eye. Previously reported mean values of about 3.5 to 4.0 nmoles per retina have been obtained using a variety of methods. The present higher values, perhaps largely dependent on procedural details described herein, appear plausible given the known concentrations of rhodopsin in rod outer segments, rod outer segment volumes, and number of rods in the human retina.

Adult

Assembly of vimentin in cultured cells varies with cell type.

To examine how vimentin assembles into the cytoskeletons of cultured cells, we used pulse labeling with [35S]methionine, cell fractionation with Triton X-100, and immunoprecipitation with a monoclonal antibody that binds both nascent and full-length vimentin polypeptides. In embryonic muscle cells, fibroblasts, and erythroid cells, we find two populations of newly synthesized vimentin. One population is found on the cytoskeleton immediately after a 2-min pulse with labeled methionine; the other is delayed in its association with the cytoskeleton and has a measurable rate of disappearance from the extractable pool. This rate varies with cell type, being over 3-fold faster in muscle and fibroblast cells than in erythroid cells. By using [3H]puromycin to specifically label nascent chains, we detect nascent vimentin chains that are bound to the cytoskeleton independently of ribosomes. The fraction of newly synthesized, full-length vimentin that associates with the cytoskeleton immediately correlates in these cell types with the fraction of nascent vimentin chains that are not released from the cytoskeleton by puromycin, RNase, or 0.6 M NaCl. Over one-half of the newly synthesized vimentin associates immediately in muscle and fibroblasts, whereas this value is less than 15% in erythroid cells. These data suggest that the process of vimentin assembly may vary both kinetically and mechanistically in different cell types.

Animals

Electrophysiologic testing techniques for children.

This practical article for clinical electrophysiologists discusses the evaluation of infant and child patients' visual systems using electroretinographic (ERG), electrooculographic (EOG), and visually evoked potential (VEP) techniques. These techniques not only help to secure specific diagnoses, but by systematic assessment of function along the visual pathways can also localize dysfunction underlying visual deficits of pediatric patients. Among children, development as well as disease can affect electrophysiological parameters. Therefore diagnosis of normal or abnormal depends critically on an adequate description of normal responses for age. Procedures that the authors have found feasible, reliable, and valid are summarized. Standardization of pediatric testing appears to be an important next step. The power of ERG, EOG and VEP recordings to demonstrate the neurophysiological basis for pediatric visual impairment is predicted to stimulate further research in this area.

Adult

Psychophysical estimates of ocular media density of human infants.

The ocular media densities of eleven 10-week-old infants and of 10 adults were estimated from dark adapted thresholds measured using a two alternative forced choice preferential looking method. The estimated media density at 400 nm derived from these thresholds ranged from 0.55 to 1.00 (median 0.75) log units for infants, and from 1.35 to 1.69 (median 1.46) log units for young adults. This indicates media density increases significantly (0.71 log units) between infancy and adulthood. These data allow more complete specification of the retinal stimulus for quantitative analysis of infants' retinal function.

Adult