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Biomedical subjects

E Pascal

Publications and source records attributed to E Pascal.

At least 19 recordsLinked to original sources
PubMed1999

Visual-proprioceptive mapping in children with developmental coordination disorder.

Developmental coordination disorder (DCD) occurs in a small but significant proportion of children who present with impaired body-eye coordination and show poor acquisition of motor skills. This study investigated the visual-proprioceptive mapping ability of children with DCD from a small selected group, with particular reference to the use of vision in matching tasks. The children with DCD in this study were significantly poorer than control children on all matching tasks. They seemed to have particular difficulty in cross-modal judgements that required the use of visual information to guide proprioceptive judgements of limb position. A distinction is drawn between tasks that can be achieved purely through sensory matching and those that require body-centred spatial judgements, suggesting that it is the latter that posits a particular difficulty for children with DCD.

Case-Control Studies↗
PubMed1998

Eye movements, prematurity and developmental co-ordination disorder.

Horizontal pursuit eye movements were investigated in two separate groups of children: One group exhibited developmental co-ordination disorder (n = 8) whilst another group of children were born prematurely (n = 8). Both studies found a reduced gain in pursuit eye movements when the respective populations were compared with control groups (n = 32). A difference was also found in the ability of some children to temporally synchronize their tracking response to the stimulus, which was indicative of poor predictive control rather than lags in the control system. We suggest that horizontal eye movements may be a sensitive indicator of more general motor deficits during childhood development.

Adult↗
PubMed1996

Visual evoked potentials in children with developmental coordination disorder.

Children who demonstrate problems with skilled movement in the absence of physical handicap are formally designated as suffering from developmental coordination disorder (DCD). Diagnosis of DCD was confirmed by the 'movement assessment battery for children'. Visually evoked potentials (VEPs) were recorded to evaluate the integrity of the visual pathway and to rule out the presence of any neurological lesions affecting visual input. Binocular, pattern onset VEPs were recorded in 14 children with DCD aged between five and seven years, and an age-matched control group using pattern onset, high contrast, grating stimuli. Implicit times to the first and second peaks and troughs were measured, and results between the two groups were compared. Inattention and movement artefact meant that VEPs were more difficult to record within the DCD group, resulting in smaller amplitudes of the waveform, but no significant differences in the implicit times were observed between the DCD group and controls. Further research is required to determine the specific source of the neurological deficits in DCD but a problem with the integrity of the afferent visual pathway does not appear to be a causal factor.

Apraxias↗
PubMed1995

Both bipartite geminivirus movement proteins define viral host range, but only BL1 determines viral pathogenicity.

Bipartite geminiviruses such as squash leaf curl virus (SqLCV) encode two movement proteins (MPs), BR1 and BL1, that are essential for virus movement and systemic infection of host plants. BR1 has been implicated in the host range properties of the virus, and BL1 in viral pathogenic properties. To more precisely examine the roles of each MP, we have introduced missense and deletion mutations into the coding sequence of both BR1 and BL1, and examined the effects of these mutations on viral infectivity and the production of disease symptoms in pumpkin, squash, and Nicotiana benthamiana. For each MP, a range of mutant phenotypes from partially to fully defective was observed that affected the overall level and rate of infectivity. However, only mutations in BL1, and not BR1, affected the severity of disease symptoms, confirming our earlier finding that BL1 is responsible for the production of disease symptoms. For all mutants, the cucurbit hosts were found to be more permissive for viral movement than was N. benthamiana, and several mutations in both BL1 and BR1 produced host-specific phenotypes, retaining high levels of infectivity in pumpkin and squash, but abolishing infectivity for N. benthamiana. Unexpectedly, functional SqLCV coat protein (AR1) was found to specifically mask the phenotypes of certain BR1 mutations, suggesting some redundancy of function between coat protein and the BR1 MP and an interaction of AR1 with the viral movement pathway. AR1 and BR1 have similar nucleic acid binding affinities, suggesting a possible mechanism for the observed effects of the viral coat protein on viral movement.

Amino Acid Sequence↗
PubMed1995

Contour interaction in the presence of congenital nystagmus.

Using a computer-generated acuity task, the resolution of vertical and horizontal Landolt Cs was assessed at three levels of contrast, each for three different crowding conditions. Eighteen adults participated; six had congenital idiopathic nystagmus, six were oculocutaneous albinos and six served as controls. Contour interaction was evident when bars were placed 1 gap-width from the Landolt C and was more marked as contrast increased. When scaled to the individual resolution limit, the magnitude of contour interaction displayed by the albinos was not significantly different from the controls, however the idiopaths did exhibit a greater crowding effect than the controls. These results imply that fixation instability is a contributory factor in contour interaction, but only when retinal image velocity is above a certain threshold.

Adolescent↗
PubMed1994

A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional activation.

Activation of transcription by the promoter-specific factor Sp1 requires coactivators that are tightly associated with the TATA-box-binding protein (TBP) in the TFIID complex. Recent work has shown that the two glutamine-rich activation domains of Sp1, A and B, can interact with at least one component of this complex, the TBP-associated factor dTAFII110. Here we report the mapping of a region of Sp1 with alternating glutamine and hydrophobic residues which is required for the interaction with dTAFII110 and is important for mediating transcriptional activation. Substitution of bulky hydrophobic residues within this region decreased both interaction with dTAFII110 and transcriptional activation in Drosophila cells. In contrast, mutation of glutamine residues in this region had no effect. Thus, the strength of the Sp1-TAF interaction correlates with the potency of Sp1 as a transcriptional activator, indicating that this activator-TAF interaction is an important part of the mechanism of transcriptional activation. Sequence comparison of three activation domains shown to bind dTAFII110 suggests that different activators that utilize dTAFII110 as a coactivator may share common sequence features that we have determined to be important for the Sp1-dTAFII110 interaction.

Amino Acid Sequence↗
PubMed1994

The geminivirus BR1 movement protein binds single-stranded DNA and localizes to the cell nucleus.

Plant viruses encode movement proteins that are essential for infection of the host but are not required for viral replication or encapsidation. Squash leaf curl virus (SqLCV), a bipartite geminivirus with a single-stranded DNA genome, encodes two movement proteins, BR1 and BL1, that have been implicated in separate functions in viral movement. To further elucidate these functions, we have investigated the nucleic acid binding properties and cellular localization of BR1 and BL1. In this study, we showed that BR1 binds strongly to single-stranded nucleic acids, with a higher affinity for single-stranded DNA than RNA, and is localized to the nucleus of SqLCV-infected plant cells. In contrast, BL1 binds only weakly to single-stranded nucleic acids and not at all to double-stranded DNA. The nuclear localization of BR1 and the previously demonstrated plasma membrane localization of BL1 were also observed when these proteins were expressed from baculovirus vectors in Spodoptera frugiperda insect cells. The biochemical properties and cellular locations of BR1 and BL1 suggest a model for SqLCV movement whereby BR1 is involved in the shuttling of the genome in and/or out of the nucleus and BL1 acts at the plasma membrane/cell wall to facilitate viral movement across cell boundaries.

Animals↗
PubMed1994

An interaction between the DNA-binding domains of RelA(p65) and Sp1 mediates human immunodeficiency virus gene activation.

Induction of human immunodeficiency virus type 1 (HIV-1) gene expression in stimulated T cells has been attributed to the activation of the transcription factor NF-kappa B. The twice-repeated kappa B sites within the HIV-1 long terminal repeat are in close proximity to three binding sites for Sp1. We have previously shown that a cooperative interaction of NF-kappa B with Sp1 is required for the efficient stimulation of HIV-1 transcription. In this report, we define the domains of each protein responsible for this effect. Although the transactivation domains seemed likely to mediate this interaction, we find, surprisingly, that this interaction occurs through the putative DNA-binding domains of both proteins. Sp1 specifically interacted with the amino-terminal region of RelA(p65). Similarly, RelA bound directly to the zinc finger region of Sp1. This interaction was specific and resulted in cooperative DNA binding to the kappa B and Sp1 sites in the HIV-1 long terminal repeat. Furthermore, the amino-terminal region of RelA did not associate with several other transcription factors, including MyoD, E12, or Kox15, another zinc finger protein. These findings suggest that the juxtaposition of DNA-binding sites promotes a specific protein interaction between the DNA-binding regions of these transcription factors. This interaction is required for HIV transcriptional activation and may provide a mechanism to allow for selective activation of kappa B-regulated genes.

Animals↗
PubMed1994

Ocular motor behaviour of monozygotic twins with tyrosinase negative oculocutaneous albinism.

The involuntary nystagmus movements of 16-year-old monozygotic twins with tyrosinase negative oculocutaneous albinism were examined. On primary gaze both girls exhibited bilateral conjugate horizontal nystagmus, a jerk with extended foveation waveform, and similar frequencies (2.0 Hz:1.9 Hz), although the fast phases were in opposite directions. The mean amplitudes differed markedly (6.8 degrees:3.7 degrees), as did the position of the null zones (+20 degrees to +30 degrees:-25 degrees to -35 degrees) and the widths of the neutral zones (-25 degrees to +20 degrees:-25 degrees to -35 degrees). Since the twins have identical genotypes these differences must have arisen from other sources.

Adolescent↗
PubMed1994

Periodic alternating nystagmus in humans with albinism.

PURPOSE: To quantify the spatial and temporal nature of congenital periodic alternating nystagmus (PAN) and to test the hypothesis that PAN results from a temporal shift in the null zone. METHODS: Twenty-five subjects with oculocutaneous albinism (16 tyrosinase negative and 9 tyrosinase positive) and 7 with ocular albinism (5 x-linked and 2 autosomal recessive) participated in the study. Using infrared oculography, five features of the nystagmus were examined: amplitude, frequency, waveform, beat direction, and temporal nature of the cycle. RESULTS: Twelve subjects (37.5%) exhibited a PAN. The nystagmus waveforms encountered during the PAN active phases were either jerk-with-extended-foveation or pseudocycloid, whereas a variety of oscillations (including triangular and bidirectional) were evident during the quiet phases. For most of the 12 subjects, there was an asymmetric variation in nystagmus intensity during each PAN cycle. None of the 12 demonstrated a convergence null or an abnormal head posture. CONCLUSIONS: PAN is not an uncommon oscillation among humans with albinism. Changes in gaze position markedly influenced the periodicity of the ongoing nystagmus, thus supporting the hypothesis that PAN is the result of a temporal shift in the null zone.

Adolescent↗
PubMed1993

Transgenic tobacco plants expressing the geminivirus BL1 protein exhibit symptoms of viral disease.

Bipartite geminiviruses, such as squash leaf curl virus (SqLCV), encode two movement proteins (MPs), BR1 and BL1, that are essential for viral movement in and subsequent infection of the host plant. To elucidate the biochemical functions of these MPs and define their respective contributions to viral infection, we have generated transgenic Nicotiana benthamiana plants expressing SqLCV BR1 and BL1. Transgenic plants expressing BR1 or a truncated BL1 were phenotypically indistinguishable from wild-type N. benthamiana. In contrast, transgenic plants expressing full-length BL1, alone or in combination with BR1, were strikingly abnormal both in their growth properties and phenotypic appearance, with leaves that were mosaic and curled under, thus mimicking typical SqLCV disease symptoms in this host. BL1 was localized to the cell wall and plasma membrane fractions, whereas BR1 was predominantly in the microsomal membrane fraction. These findings demonstrate that expression of BL1 in transgenic plants is sufficient to produce viral disease symptoms, and they further suggest that BL1 and BR1 carry out distinct and independent functions in viral movement.

Base Sequence↗
PubMed1993

Incremental light detection thresholds across the central visual field of human albinos.

PURPOSE: The authors investigated central retinal function in albinism by measuring incremental light detection thresholds in a group of oculocutaneous human albinos. METHODS: Eleven oculocutaneous human albinos (six tyrosinase negative and five oculocutaneous positive), six patients with idiopathic congenital nystagmus, and six normal control subjects participated in the study. Using a Goldmann bowl perimeter, incremental light detection thresholds were measured in the vertical meridian across the central +/- 30 degrees of the retina. Target presentation times were 1 sec for all subjects, and in the case of four albinos and one patient with idiopathic nystagmus, they were limited to the low-velocity period of each nystagmus cycle. RESULTS: For the normal control subjects, the maximum sensitivity was found to be -0.60 +/- 0.10 log units. By comparison, at 0 degrees, a range of sensitivities was obtained from the albino subjects (-0.9 to -2.1 log units) and from those with idiopathic nystagmus (-0.7 to -1.9 log units). The albinos had diverse retinal sensitivity profiles ranging from a near-normal peaked curve to a flat homogeneous profile. A variety of sensitivity profiles was also detected in those with idiopathic nystagmus, although, compared with the albino curves, a greater proportion were peaked. No sensitivity differences were found between the short and the longer target presentations. CONCLUSIONS: The variety of retinal sensitivity profiles obtained in this study suggests that, in albinism, considerable intersubject variability in the degree of foveal hypoplasia exists and that albino "foveal" function can reach near-normal levels, for at least some visual tasks.

Adolescent↗
PubMed1991

Visual resolution limits in human albinism.

The effects of the involuntary ocular oscillations on visual resolution was examined in 22 albinos and 11 idiopaths with congenital nystagmus. The idiopaths showed a linear relationship between the proportion of the slow phase spent at low velocities (less than or equal to deg/sec) and the log of the minimum angle of resolution; such that long dwell times were compatible with good resolution. For the albinos there appeared to be a critical duration of low retinal slip velocities above which there was no improvement in acuity. This supports the contention that factors other than the congenital nystagmus limit visual resolution in the albino.

Albinism, Ocular↗
PubMed1991

The effects of simultaneous central and peripheral field motion on the optokinetic response.

The effects of central and peripheral retinal stimulation on the optokinetic response were examined using full-field, central field only, peripheral field only and simultaneous central and peripheral field motion. Stimulation of the central field in isolation produced similar responses to those obtained for full-field motion whereas peripheral field stimulation resulted in greatly reduced responses. Central field dominance was also evident during central and peripheral field motion in opposing directions. However with unidirectional, simultaneous central and peripheral stimulation the optokinetic response was determined not by the central stimulus but by whichever stimulus moved the slower.

Adult↗
PubMed1991

Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism.

The process of transcriptional activation in eukaryotes by site-specific DNA-binding proteins is a key step in gene regulation. Here we have examined the properties of four distinct activator domains of the human transcription factor Sp1. In vivo transient cotransfection assays with Sp1 show that templates bearing multiple Sp1 sites activate transcription with a high degree of synergism. However, there is no evidence of cooperative binding of Sp1 to adjacent sites. Using deletion mutants of Sp1 we have determined that the glutamine-rich activation domains A and B and the previously uncharacterized carboxy-terminal domain D are all required for Sp1 to activate transcription synergistically. Gel-shift, DNase footprinting, and chemical cross-linking experiments reveal a strong correlation between the ability of Sp1 mutants to form homomultimeric complexes and their ability to activate transcription synergistically when bound to multiple sites. We have also examined the process of superactivation, in which a molecule of Sp1 tethered to DNA via its zinc fingers can be transcriptionally enhanced by interacting directly with fingerless Sp1 molecules. The domains involved in superactivation appear to be a subset of those necessary to achieve synergistic activation. These findings suggest that different domains of Sp1 carry out distinct functions and that the formation of multimeric complexes may direct synergism and superactivation.

Animals↗
PubMed1990

Retinal image quality in albinos. A review.

This paper describes two of the factors which affect retinal image quality in oculocutaneous albinos. Contrast detection thresholds were determined to quantify the effects of intra-ocular light scatter and the consequences of continuous retinal image motion. The implications of these results on the limits of visual performance are discussed in the light of the accompanying foveal hypoplasia.

Albinism, Oculocutaneous↗
PubMed1989

Retinal fixation behavior in human albinos.

The retinal fixation behavior of 17 albinos was examined whilst they fixated a stationary target. An optical system was arranged so that the motion of the target on the retina, due to the nystagmus, could be video-recorded. Eye movements were monitored simultaneously. Eight of the 17 subjects were judged to use consistently a retinal location compatible with the anatomical position of the fovea. The implications of this for subjects with foveal hypoplasia are discussed.

Adolescent↗