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Biomedical subjects

D Maurice

Publications and source records attributed to D Maurice.

At least 19 recordsLinked to original sources
PubMed2002

Automated detection of low-dimensional EEG alpha-episodes. An example of application to psychopharmacological data.

This paper addresses the practical problems raised by the fact that correlation integrals computed from electroencephalographic signals do not scale. An automated procedure is described for alpha-waves, which is based on the known method of determining the correlation dimension from scaled structures that appear in diagrams of slope-curves. Automation, which is achieved using a moving window that detects the minima of slope-curves, and the density of minima makes it possible to vary the numerous parameters, and to implement tests. The potentialities of the automatic procedure are illustrated by results of psychopharmacological interest, based on the analysis of 22x10(3) alpha-signals, and the computation of 32x10(6) correlation integrals. Previous results concerning the existence of low-dimensional alpha-episodes, lasting in general not more than 5-6 s, are confirmed. Opposing effects upon the correlation dimension are described, at their pharmacological peak, for a dopaminergic agonist (apomorphine) and an atypical antipsychotic, a sigma-receptor ligand. The results also confirm that time reparametrization is a vital check in searches of low-dimensional attractor-ruled dynamics, and they suggest that subjects exhibiting 'high-alpha', i.e. whose alpha-waves are of amplitude A>30 microV, be selected for such investigations.

Adolescent↗
PubMed2001

Loss of Smad4 function in pancreatic tumors: C-terminal truncation leads to decreased stability.

At early stages of tumorigenesis, the transforming growth factor-beta (TGF-beta) signaling pathway is thought to have tumor suppressor activity as a result of its ability to arrest the growth of epithelial cells. Smad4 plays a pivotal role in the TGF-beta signaling pathway and has been identified as a tumor suppressor, being mutated or deleted in approximately 50% of pancreatic carcinomas and 15% of colorectal cancers. A nonsense mutation generating a C-terminal truncation of 38 amino acids in the Smad4 protein has been identified in a pancreatic adenocarcinoma (Hahn, S. A., Schutte, M., Hoque, A. T., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., and Kern, S. E. (1996) Science 271, 350-353), and here we investigate the functional consequences of this mutation. We demonstrate that the C-terminal truncation prevents Smad4 homomeric complex formation and heteromeric complex formation with activated Smad2. Furthermore, the mutant protein is unable to be recruited to DNA by transcription factors and hence cannot form transcriptionally active DNA-binding complexes. These observations are supported by molecular modeling, which indicates that the truncation removes residues critical for homomeric and heteromeric Smad complex formation. We go on to show that the mutant Smad4 is highly unstable compared with wild type Smad4 and is rapidly degraded through the ubiquitin-proteasome pathway. Consistent with this, we demonstrate that the pancreatic adenocarcinoma harboring this mutated allele, in conjunction with loss of the other allele, expresses no Smad4 protein. Thus we conclude that these tumors completely lack Smad4 activity.

3T3 Cells↗
PubMed2001

Review: practical issues in intravitreal drug delivery.

The delivery of drugs to the retina from solution or from prolonged release forms is considered in terms of pharmacokinetics, interference with vision, and toxicity and safety. It is concluded that visual loss will be the limiting factor in determining the useful life of a drug administered as a microdispersion. Because microparticles can be lost from the vitreous by diffusion, a condensed depot of drug can give a greater lifetime. However, it needs to be anchored outside the visual pathway which requires an intraocular operative procedure. Attaching a reservoir to the external sclera with a diffusion-controlled entry through a tube to the vitreous is suggested as having more flexibility than other systems.

Animals↗
PubMed1998

The activity of Sendai virus genomic and antigenomic promoters requires a second element past the leader template regions: a motif (GNNNNN)3 is essential for replication.

The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions. These leader template regions, present at the 3' end of the genome and the antigenome, have been shown to contain essential signals governing RNA replication activity. Whether they are sufficient to promote replication is still open to question. By using a series of Sendai virus defective interfering RNAs carrying a nested set of deletions in the promoter regions, it is shown here that for both the genomic and antigenomic promoters, a 3'-end RNA sequence of 96 nucleotides is required to allow replication. Sequence comparison of active and inactive promoters led to the identification of a set of three nucleotide hexamers (nucleotides 79 to 84, 85 to 90, and 91 to 96) containing a repeated motif RXXYXX [shown as 5'-3' positive-strand]. Sequential mutation of each hexamer into its complementary sequence confirmed their essential role. The three hexamers are required, and their relative positioning is important, since displacing them by 6 nucleotides destroyed promoter function. RNAs carrying degenerate nucleotides in the three hexamers were used as replication templates. They led to the selection of actively replicating RNA species exclusively carrying the basic motif (GNNNNN)3 from nucleotides 79 to 96. These results clearly show that, apart from the region from nucleotides 1 to 31, previously identified as governing Sendai virus replication activity, a second element, spanning at the most nucleotides 79 to 96, appears essential. Thus, the paramyxovirus replication promoters are not confined to the leader template regions, as seems to be the case for the rhabdoviruses.

Binding Sites↗
PubMed1996

A new method for determining corneal epithelial barrier to fluorescein in humans.

PURPOSE: To derive the value of corneal epithelial barrier to fluorescein in humans from experiments in which the fluorophore in instilled in a single drop. METHOD: A commercial scanning fluorophotometer, the Fluorotron Master, was used to scan through an anterior segment. It could not resolve the tear film from the cornea, but in the early stages of measurement, the tear component predominated. After 20 minutes, the remaining fluorescein was washed out of conjunctival sac, and the amount that penetrated into the cornea was estimated. Because the resolution was not sufficient to estimate the concentrations, the total masses in the tear film and in the cornea derived from the area under the profile were used to calculate the epithelial permeability. A value for the tear film thickness had to be assumed. RESULTS: The technique led to reproducible values for epithelial permeability-a range of 2:1 in a subject. High concentrations of fluorescein were required to achieve a sufficient penetration into the cornea, and this led to error in estimating the tear film concentration of the dye. A method is presented that corrects for this effect. For 17 normal subjects, the corrected permeability was 0.15 nm/second, and the tear turnover was 0.15/minute ( +/- 0.016, standard error.) CONCLUSIONS: This technique is convenient and yields two useful physiological parameters from a single clinical procedure. The permeability values are considerably higher than those found by previous workers, and the source of the discrepancy is discussed.

Absorption↗
PubMed1995

The effect of the low blink rate in rabbits on topical drug penetration.

PURPOSE: The low rate of blinking in the rabbit as compared to the human suggests that there may be a greater contact time for drugs applied topically in the animal. However, there have been no experiments performed to examine this belief directly. METHODS: A small drop containing either fluorescein or FITC Dextran was applied to the eye of a rabbit without the use of tranquilizer or anesthetic. Subsequently, the change in the fluorescence of the precorneal tear film was followed with a noninvasive fluorometer. RESULTS AND CONCLUSION: The animal did not blink for 20-30 min. after the instillation. With either fluorophore, the tear film fluorescence remained constant after the first few minutes and fell precipitously at the first blink. Comparison with the loss kinetics in the human eye, an exponential decline with an average rate constant of 0.16 min-1, indicates that the AUC will be 3 times greater in the rabbit, and the penetration of a drug can be overestimated to the same degree from the low blink rate alone. There was a rise in the corneal fluorescence, attributable to penetration of the fluorophore, after the eye was washed at the end of the experiment. This was used to estimate the epithelial permeability which averaged 1.5 x 10(-4) cm hr for fluorescein and 1.9 x 10(-5) cm hr-1 for FITC Dextran. For most drugs, however, the epithelial permeability is sufficiently high that all the material present in the tear film will partition into the cornea in a few minutes. Considerations of contact time become irrelevant under these circumstances.

Absorption↗
PubMed1988

Bicarbonate sensitivity of rabbit corneal endothelium fluid pump in vitro.

Stroma-endothelium preparations from rabbit corneas were mounted between two chambers and incubated with identical media on either side which contained different bicarbonate levels and, in some experiments, organic (Good's) buffers. Active fluid flow across the preparations was measured by means of a capillary tube attached to the stroma-side chamber. With media containing 2 to 50 mM bicarbonate (pH 6.2 to 7.8 in equilibrium with 5% CO2-air at 37 degrees C), the fluid pump was constant for at least 3 hr at a rate of 5 microliter/hr cm2 and was not significantly affected by the bicarbonate level. Over the same range of pH and bicarbonate but supplemented with 50 mM organic buffer, fluid pump was 8 microliter/hr cm2 for all bicarbonate concentrations used. Using Ringer solutions supplemented with 50 mM buffer (pH 6.3 to 8.4) but without added bicarbonate and in equilibrium with air, fluid pump was observed at approximately 4 microliter/hr cm2 at pH 6.3 and increased to 8 microliter/hr cm2 at pH 7.8. In all cases, fluid pump persisted for at least 5 hr.

Animals↗