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Biomedical subjects

B L Scott

Publications and source records attributed to B L Scott.

At least 37 records · Page 2Linked to original sources

Human apolipoprotein E accelerates microtubule polymerization in vitro.

Apolipoprotein E (apoE) is a 34-kDa protein implicated in Alzheimer's disease (AD) that has recently been identified in neuronal cytoplasm. In cultured neurons, the two major isoforms of apoE (E3 and E4) differentially affect neurite extension, microtubule formation, and the ratio of polymerized to depolymerized tubulin. We therefore examined the effects of apoE3 and apoE4 on microtubule assembly in vitro. ApoE3 and apoE4 equally accelerated microtubule polymerization under conditions of slow microtubule assembly. Controls comprising apolipoprotein A1, bovine serum albumin, trypsin inhibitor, and boiled apoE had no effect, demonstrating specificity of the apoE effect. The ability of both apoE isoforms to accelerate microtubule assembly in vitro suggests that isoform-specific differences in neurite extension may result from differences in the uptake, intracytoplasmic transport, or metabolism of these isoforms.

Animals↗

Botulinum toxin injection into vocal cord in the treatment of malignant coprolalia associated with Tourette's syndrome.

We describe a 13-year-old boy with Tourette's syndrome (TS) manifested chiefly by severe coprolalia, obsessive compulsive disorder, and attention deficit hyperactivity disorder. He was treated with unilateral injections of botulinum toxin to the vocal cord and experienced marked improvement in coprolalia as well as marked reduction in the premonitory urges associated with the vocal tics and coprolalia. As a result of the improvement, the patient was able to attend school and church and was able to socialize. Botulinum toxin may interfere with a sensory reflex arc required to perpetuate tics and coprolalia in TS, possibly by reducing local build-up of tension or muscle contraction in affected areas.

Adolescent↗

Delayed-onset progressive movement disorders after static brain lesions.

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Adult↗

Dietary omega-3 fatty acids and accumulation of docosahexaenoic acid in rod photoreceptor cells of the retina and at synapses.

Docosahexaenoic acid (DHA), the major biosynthetic product of the omega-3 family of fatty acids, is uniquely concentrated in the retina and synaptic membranes. In the perinatal period of life, when the bulk of synaptogenesis and photoreceptor biogenesis takes place, large requirements of DHA may be met first by the placenta and then by maternal milk. Linolenic acid (LLA), the precursor of DHA, is the most prevalent fatty acid of the omega-3 series in the stomach contents of newborn mice. In this study we have investigated the fate of radiolabeled LLA and DHA injected intraperitoneally in developing postnatal mouse. Our results show that radiolabeled LLA was taken up by the liver and DHA was synthesized; at 72 hrs post-injection about 90% of the label had been converted to DHA. Since there was a time-dependent buildup of radiolabeled DHA in blood plasma with negligible early uptake of LLA by the brain and retina, we hypothesize that the liver may secrete lipoproteins containing DHA and that this process is regulated by the nervous tissue.

Animals↗

Membrane docosahexaenoate is supplied to the developing brain and retina by the liver.

Docosahexaenoic acid [22:6 omega 3; 22:6(4, 7, 10, 13, 16, 19)] is concentrated in phospholipids of cellular membranes from brain and retina. Although linolenic acid [18:3 omega 3; 18:3(9, 12, 15)] is the major omega 3 fatty acid of mouse dams' milk, 22:6 is the prevalent omega 3 fatty acid in serum and tissues. Intraperitoneal injection of [1-14C]18:3 into 3-day-old mouse pups resulted in liver and serum lipid labeling that was initially high, followed by a rapid decline. In contrast, labeling of brain and retinal lipids were initially low and increased with time. Labeled 22:6 first appeared in liver 2 hr after injection and later in brain and retina. We suggest that 22:6 synthesized from 18:3 by the liver is secreted into the bloodstream in lipoproteins, taken up by brain and retina, and incorporated into cell membranes. We hypothesize that the 22:6 requirements of membranes (e.g., during synaptogenesis, photoreceptor membrane biogenesis, or repair after ischemic injury or neurodegenerative disorders) are met by a signal that is sent by the appropriate tissues to the liver to evoke the secretion of 22:6-containing lipoproteins.

Animals↗

Developing rod photoreceptors from normal and mutant Rd mouse retinas: altered fatty acid composition early in development of the mutant.

The phospholipid and fatty acid contents of developing rod photoreceptor cells were determined in dissociated photoreceptor cells obtained from normal mice and from rd mice exhibiting an inherited retinal degeneration. Photoreceptors were dissociated from retinas by mechanical agitation after mild protease treatment and characterized by light and electron microscopy. Phospholipid classes were isolated by thin-layer chromatography, and fatty acyl groups separated and quantitated by capillary gas-liquid chromatography. Developing photoreceptor cells of normal retinas accumulated all phospholipid classes, but in proportions which shifted with age. The mole % contents of phosphatidylcholine (PC) and phosphatidylinositol (PI) decreased with age, whereas phosphatidylethanolamine (PE) and phosphatidylserine (PS) increased. The content of the polyunsaturated fatty acid docosahexaenoate (22:6), expressed as nmol/microgram lipid phosphorus, increased rapidly during development, whereas arachidonate (20:4) content tended to decline. Mono-unsaturated fatty acid levels (palmitoleate, 16:1; oleate, 18:1) declined with age. Among saturated fatty acids, palmitate (16:0) decreased during normal development, whereas stearate (18:0) increased. The total mass of phospholipid/photoreceptor cell in the normal, adult mouse retina was estimated to be approximately 14 pg. The total phospholipid content and mole % distribution of individual phospholipid classes in immature rd photoreceptors were similar to values for normal cells. In contrast, significant changes in fatty acid composition were detected between immature rd cells and normal cells. Rd cells generally had higher levels of saturated (myristate, 14:0; palmitate, 16:0) and monounsaturated fatty acids (oleate, 18:1) and lower levels of polyunsaturated fatty acids (arachidonate, 20:4; docosahexaenoate, 22:6), suggesting that fatty acid metabolism is altered by expression of the rd gene and/or by the associated impairment of photoreceptor cell differentiation.

Animals↗

Docosahexaenoate metabolism and fatty-acid composition in developing retinas of normal and rd mutant mice.

The fatty-acid composition of retinal lipids in developing control and rd mice (C57BL/6J) was determined. In addition, fatty-acid composition in brain and retina of normal and rd adult animals was compared. At 11 days of postnatal age, rd retinas contained proportionally less docosahexaenoate than controls, whereas the reverse relationship held for oleate at 20 days of age. In contrast, no differences in the fatty-acid composition of brain lipids were observed between rd and control animals. We also examined docosahexaenoate metabolism in rd and control retinas of different postnatal ages in vitro. These studies of [1-14C]docosahexaenoic-acid incorporation into retinal phospholipids and neutral lipids demonstrated significantly higher incorporation into triacylglycerols of the rd retina, beginning at 14-15 days of postnatal age. Incorporation into diacylglycerols and phospholipids was also higher in rd retinas than in controls at 14 days of age and older. Moreover, the concentration of ganglioside (a glycolipid class probably enriched within inner retinal layers) was higher in adult rd retinas. Degeneration of the rd retina can be detected histologically as early as 8-9 days. Therefore, the alterations of fatty-acid composition and docosahexaenoate metabolism described here are probably an effect, rather than a cause, of retinal degeneration in the rd mouse.

Aging↗

Decreased content of docosahexaenoate and arachidonate in plasma phospholipids in Usher's syndrome.

Docosahexaenoate and arachidonate were found to be significantly decreased in plasma phospholipids from Usher's syndrome patients. The fatty acid content of plasma triacylglycerols was not changed in these patients. Usher's syndrome, an autosomal recessive disorder, involves an inherited visual cell degeneration. Photoreceptor membranes are richly endowed with docosahexaenoate and arachidonate, and a metabolic defect affecting these polyunsaturated fatty acids may occur. Moreover, blindness may be due, at least partially, to an alteration in the unsaturated phospholipids of photoreceptor membranes.

Arachidonic Acid↗

Two-dimensional rhodopsin crystals from disk membranes of frog retinal rod outer segments.

Two-dimensional crystals of rhodopsin have been prepared from purified frog disk membranes by using the detergent Tween 80. The space group of the orthorhombic crystals is p22121; the unit cell dimensions are 47 X 151 A. Projection maps of negatively stained preparations have been calculated to a resolution of approximately 22 A. The rhodopsin molecules are associated as dimers that appear to be slightly sigmoidal and are 20-25 A in width and 70-80 A in length.

Animals↗

Increasing the intelligibility of sung vowels.

The intelligibility of the front vowels (/i/, /I/, /epsilon/, and /ae/) was investigated as sung in four different ways: (1) operatic, (2) in consonant-vowel-consonant (CVC) context, (3) with a raised larynx, and (4) with both raised larynx and in CVC context. Al syllables were sung by a trained soprano at F4, A4, C sharp 5, F5, A5, and C sharp 6. Ten subjects listened and identified randomized sets of ten tokens of each vowel per condition (method of articulation) at each note. Results showed that, from C sharp 5 (nominal 554 Hz) to F5 (698 Hz), the intelligibility of operatic vowels (condition 1) fell from 56% to 16%. The mean intelligibility of the vowels at the three highest notes (F5, A5, C sharp 6) was 10% for condition 1, 64% for condition 2, 62% for condition 3, and 83% for condition 4. Results indicate that increased intelligibility across conditions is a function of increased energy in the higher harmonics and presence of consonantal transitions. The generally accepted notion that vowel sounds are largely unintelligible on higher notes pertains only to a restricted manner of production.

Humans↗

A method for training and evaluating the reception of ongoing speech.

The "tracking procedure" is a method to train and evaluate the reception of ongoing speech. A talker and a receiver engage in a dialogue for a designated period of time in which the receiver reports his perception of successive segments of read text and is corrected by the talker until the text is repeated verbatim. Performance is measured in number of words of text repeated correctly per unit of time. The procedure is illustrated by its application to a project for training and evaluating use of a vibrotacile-electrotactile aid to lipreading. Differences between experimental conditions are described over time in terms of absolute words per minute, increment of aided over unaided words-per-minute scores, and percent of normal listening rate. Data from identification tests with syllables, words, and sentences are also presented. Tracking is suggested as an additional procedure for communication training in aural rehabilitation or classroom setting, and for evaluation of other communication systems.

Auditory Perception↗