Timing of levodopa therapy: evidence from MPTP-treated primates.
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Biomedical subjects
S Boyce
Publications and source records attributed to S Boyce.
Application of MRI to the analysis of speech production.
Computer models of the process of speech articulation require a detailed knowledge of the vocal tract configurations employed in speech and the application of acoustic theory to calculate the sound waveform. Almost all currently available data on vocal tract dimensions come from x-ray films and are severely limited in quantity and coherence due to restrictions on radiation dosage and intersubject differences. We are using MRI techniques to obtain the pharyngeal dimensions of speakers producing sustained vowels. The fact that MRI does not employ ionizing radiation provides speech research with the opportunity to obtain comprehensive bodies of much-needed data on the articulatory characteristics of single subjects.
Fourier Analysis↗
Grammatical information effects in auditory word recognition.
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Humans↗
MPTP-induced parkinsonism in the monkey: neurochemical pathology, complications of treatment and pathophysiological mechanisms.
MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of levodopa over 4-8 weeks leads to the emergence of "peak-dose" dyskinesia. Such abnormal movements are not seen following challenge doses of levodopa in animals not on long-term therapy. Radioligand studies reveal a 40-180% increase in D2 receptor binding in the striatum of parkinsonian monkeys. 2-deoxyglucose studies of regional brain metabolism indicate that MPTP-induced parkinsonism is characterised by abnormally increased activity of medial pallidal neurones which project to the thalamus and pedunculopontine nucleus and reduced activity of subthalamic nucleus neurones.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Alterations in [Met5]- and [Leu5]enkephalin and neurotensin content in basal ganglia induced by the long-term administration of dopamine agonist and antagonist drugs to rats.
Treatment of rats for 18 months with trifluoperazine increased [Met5]- and [Leu5]enkephalin and neurotensin content in striatum and nucleus accumbens. However, in substantia nigra the content of [Met5]enkephalin was decreased, [Leu5]enkephalin unchanged and that of neurotensin increased. Administration of L-DOPA plus carbidopa, bromocriptine or pergolide for 12 months decreased [Met5]enkephalin (except bromocriptine) and neurotensin, but not [Leu5]enkephalin, levels in striatum. L-DOPA decreased and bromocriptine increased neurotensin levels in substantia nigra. But neurotensin levels in nucleus accumbens were unaffected.
Animals↗
SCH 23390 may alter dopamine-mediated motor behaviour via striatal D-1 receptors.
SCH 23390 potently displaced the specific binding of 3H-piflutixol to D-1 sites in striatal membranes but haloperidol was only weakly effective. SCH 23390 weakly displaced specific 3H-spiperone binding to D-2 sites, but haloperidol was potent. SCH 23390 was more effective than haloperidol in inhibiting dopamine stimulated striatal adenylate cyclase activity. These results confirm the D-1 selectivity of SCH 23390. However, SCH 23390 inhibited apomorphine-induced stereotypy and climbing behaviour in rats with equal potency to haloperidol. Haloperidol dose-dependently increased striatal HVA and DOPAC concentrations without altering dopamine content. Low doses of SCH 23390 elevated striatal DOPAC concentrations but higher doses were without effect; striatal dopamine and HVA overall was unaffected by administration of SCH 23390. Haloperidol did not affect basal 3H-acetylcholine release from striatal slices but reversed the apomorphine-induced inhibition of 3H-acetylcholine release. SCH 23390 did not affect basal 3H-acetylcholine release nor did it reverse the apomorphine-induced inhibition of 3H-acetylcholine release. The ability of SCH 23390 to inhibit motor behaviour in the rat may be due to its action on D-1 receptors since the drug does not cause typical changes in parameters of striatal D-2 receptor function.
3,4-Dihydroxyphenylacetic Acid↗
Repeated administration of N-methyl-4-phenyl 1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones.
N-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine ( MPTP ) (10 mg/kg/day i.p.) was administered to rats for 16 days, which were then observed for a further 9-11 days. MPTP administration did not alter spontaneous locomotor activity or amphetamine (2.5 mg/kg ip)-induced locomotion. Apomorphine (0.25 mg/kg sc) did not alter locomotion in control rats but increased activity in MPTP treated animals. The stereotyped response to apomorphine (0.25 mg/kg sc) and amphetamine (2.5 and 5.0 mg/kg ip) was unaltered by MPTP administration. The striatal content of dopamine, HVA and DOPAC was unaltered by MPTP intake. The uptake of [3H]dopamine and [3H] 5HT in striatal synpatosomes was not changed by MPTP . The results suggest that MPTP , in the dose used, is not toxic to nigro-striatal dopamine neurones in the rat. This contrasts with its neurotoxic actions in monkeys and man.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Isochromosome 6p, a unique chromosomal abnormality in retinoblastoma: verification by standard staining techniques, new densitometric methods, and somatic cell hybridization.
Study of chromosome rearrangements in retinoblastoma tumors revealed that all tumors contained either an unusual isochromosome and/or extra copies of chromosome 1q. Extra copies of chromosome 1q occur in many malignancies. The pattern of G-bands suggested that the isochromosome was derived from either the short arm of chromosome 6, i(6p), or the long arm of chromosome 17, i(17q). Standard staining techniques using G-, C-, Q-, and R-banding; high resolution G-banding; and density profile analysis were consistent with the characteristic isochromosome of retinoblastoma being i(6p), rather than i(17q). This conclusion was substantiated by the analysis of segregants derived from retinoblastoma X mouse hybrid cells which had been grown in bromodeoxyuridine to select for loss of chromosome 17. The unique isochromosome was not lost under these conditions confirming that it is an i(6p) rather than an i(17q). The i(6p) abnormality has not been observed frequently in other tumors, but occurs in 60% of retinoblastoma tumors. Thus, although the mutation predisposing to retinoblastoma is known to map at 13q14, somatic amplification of genes on 1q and 6p may play a role in the pathogenesis of this tumor.
Animals↗
Interpretation of changes in apomorphine-induced stereotyped behaviour in rats receiving continuous administration of trifluorperazine for 15 months.
Rats treated continuously with trifluoperazine dihydrochloride (4.4-4.9 mg/kg per day) for 15 months showed an exaggerated stereotyped response to large doses of apomorphine (1.0 mg/kg, s.c.), but inhibition of stereotyped behaviour by a small dose of apomorphine (0.125 mg/kg, s.c.) as compared to responses obtained in age-matched control animals. Apomorphine (0.03-1.0 mg/kg, s.c.) produced more hyperactivity in trifluoperazine-treated rats than in control animals. After withdrawal of the drug for a period of 2 weeks or more, the stereotyped responses to all doses of apomorphine (0.0625-0.5 mg/kg, s.c.) were exaggerated in animals treated with trifluoperazine compared with age-matched control rats. Acute administration of trifluoperazine (4.5 mg/kg, p.o., 3 hr previously) to animals withdrawn from trifluoperazine abolished the stereotyped behaviour induced by a small dose of apomorphine (0.125 mg/kg) but a maximal response still was obtained with large doses (1.0 mg/kg). In contrast, acute challenge with trifluoperazine (4.5 mg/kg, p.o.) in control animals inhibited the stereotyped behaviour at virtually all doses of apomorphine, as compared with the responses to apomorphine in both animals withdrawn from trifluoperazine, given the same treatment, and naive control rats. Administration of trifluoperazine (0.28 and 0.56 mg/kg, p.o.) inhibited stereotypy induced by small doses of apomorphine (0.125 mg/kg, s.c.) in control animals but the response in animals withdrawn from trifluoperazine was exaggerated. Larger doses of trifluoperazine (1.125-4.5 mg/kg) totally inhibited apomorphine-induced (0.125 mg/kg, s.c.) stereotypy in both groups. These findings do not support the concept of separate mechanisms controlling low grade and high grade stereotyped behaviour during chronic treatment with neuroleptics.
Animals↗
Declination of fundamental frequency in speakers' production of parenthetical and main clauses.
An experimental study was conducted to investigate fundamental frequency (F0) contours in sentences with and without parenthetical clauses. Sentences consisted of a systematically lengthened parenthetical clause inserted between the subject noun phrase and the verb phrase of the main clause. The middle portion of the parenthetical was lengthened incrementally in each sentence to test the effects of sentence length on fundamental frequency contours of seven test sentences. Computer-aided measurements were made for: F0 peaks of key stressed segments; duration of the main clause, parenthetical clause, and clause-final syllables within each; and pauses immediately preceding and following the parenthetical. Mean results demonstrate: (1) a drop in F0 for the parenthetical clause, well below the main clause declination and forming a separate contour of declination; (2) a sharp rise in F0 on return to the main clause; (3) no effect of longer parenthetical length on final segment durations of either the parenthetical or the main clause; and (4) no effect of increased parenthetical length on main clause duration or pause length. These results suggest that parenthetical clauses are mentally programmed as independent constituents, but are subject to some of the same general declination constraints as main clauses.
Humans↗
Modification of the Helena electrophoretic procedure for urinary VMA for paediatric purposes.
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Child↗
Epidermal lipid metabolism of cultured skin substitutes during healing of full-thickness wounds in athymic mice.
Cultured epidermal keratinocytes provide an abundant supply of biologic material for wound treatment. Because restoration of barrier function is a definitive criterion for efficacy of wound closure and depends on the lipids present in the epidermis, we analyzed lipid composition of the epidermis in cultured skin substitutes in vitro and after grafting to athymic mice. The cultured skin substitutes were prepared from human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates. After 14 days of incubation, cultured skin substitutes were grafted orthotopically onto full-thickness wounds in athymic mice. Samples for lipid analysis were collected after 14 and 34 days of in vitro incubation, and 3 weeks and 4 months after grafting. Both in vitro samples show disproportions in epidermal lipid profile as compared with the native human epidermis, i.e., a low amount of phospholipids (indicating imbalance in proliferation and differentiation); a large excess of triglycerides (storage lipids); and low levels of free fatty acids, gluco-sphingolipids, cholesterol sulfate, and ceramides-suggesting abnormal composition of stratum corneum barrier lipids. Fatty acid analysis of cultured skin substitutes in vitro revealed insufficient uptake of linoleic acid, which resulted in increased synthesis of and substitution with monounsaturated fatty acids, mainly oleic acid. These abnormalities were partially corrected by 3 weeks after grafting; and 4 months after grafting, all epidermal lipids, with some minor exceptions, were synthesized in proportions very similar to human epidermis. Results of this study show that grafting of cultured skin substitutes to a physiologic host permits the recovery of lipid in proportion to that required for barrier formation in normal human epidermis.
Journal Article↗
Tissue donation: the benefit of a positive approach.
Unlike organ donation, which enjoys a worthy public profile, tissue transplantation remains relatively unheard of. Here, the authors argue that nurses should promote the value of tissue donation, not only to patients but to colleagues as well.
Contraindications↗