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Biomedical subjects

T Ohlmann

Publications and source records attributed to T Ohlmann.

At least 19 recordsLinked to original sources
PubMed2006

Perception of longitudinal body axis in patients with stroke: a pilot study.

BACKGROUND AND AIMS: To investigate the hypothesis that patients with a hemisphere stroke may perceive their longitudinal body axis (LBA) rotated in the frontal plane. This error in an egocentric frame of reference could be detrimental to posture, as tilted LBA would imply an unequal distribution of body mass about the true vertical. METHOD: 26 healthy subjects matched in age with 18 patients living with stroke participated in the study. The 18 patients were tested on average 80 days after a first left (n = 8) or right (n = 10) hemisphere stroke. Participants perceived their LBA by adjustments of the orientation of a luminous rod pivoting around a dorsonavel axis to the subjective direction of LBA. Participants were studied in the supine position to dissociate somaesthetic cues from graviceptive cues. RESULTS: Patients with stroke perceived their LBA rotated to the contralesional side in comparison with controls (p = 0.004). For all controls and 10 patients with stroke, the perceived LBA was very close to true LBA (mean (SD) 0.24 degrees (1.31 degrees)). For eight patients with stroke (six right stroke, two left stroke), the perceived LBA was rotated from true body orientation in the direction opposite to the lesioned side (range 3-9.5 degrees, mean 5.2 degrees). These eight patients provided similar estimates by tactile manipulation of the rod (without vision). The rotation of perceived LBA was more pronounced for right-hemisphere strokes. The magnitudes of perceptual rotations correlated with sensory loss, signs of spatial neglect and the degree of postural and gait disability. CONCLUSION: This is the first study showing that certain patients with a hemisphere stroke perceive their LBA rotated to the contralesional side. The consequences for perceptuomotor coordination have implications for their postural disorders.

Aged↗
PubMed2000

An internal ribosome entry segment promotes translation of the simian immunodeficiency virus genomic RNA.

The retroviral genomic RNA is the messenger for the synthesis of the group-specific antigen (gag) and polymerase precursors of the major structural proteins and enzymes of the virion. The 5'-untranslated leader of the simian immunodeficiency virus (SIV) genomic RNA is formed of highly structured domains involved in key steps of the viral life cycle. Thus, the presence of stable RNA structures between the 5'-cap and the gag start codon are thought to strongly inhibit scanning of a 43 S preinitiation ribosomal complex. This prompted us to look for an alternative to the canonical ribosome scanning. By using a standard bicistronic assay in the rabbit reticulocyte lysate, we show that the SIVmac 5'-leader contains an internal ribosome entry segment (IRES) and that gene expression driven by this IRES is stimulated upon cleavage of eukaryotic initiation factor 4G. Deletion analysis revealed that the sequence between the major splice donor and the gag AUG codon is required for IRES activity. DNA transfection and viral transduction experiments in both NIH-3T3 and COS-7 cells confirmed that translation driven by the SIV leader is IRES-dependent and thus insensitive to the immunosuppressant rapamycin. Identification of an IRES in SIV is of particular interest for the understanding of lentivirus replication and also for the design of novel lentiviral vectors suitable for gene transfer.

3T3 Cells↗
PubMed2000

The role of neck afferents in subjective orientation in the visual and tactile sensory modalities.

We studied the influence of neck afferents on the perception of orientation. In Experiment 1, we investigated the effect of head tilt on the subjective vertical in both the visual and tactile modalities. The results showed that head tilt triggers an Aubert effect in the visual modality and a Müller effect in the tactile modality. Significant positive correlations between the two adjustment modalities were restricted to head tilt to the left. In Experiment 2, we investigated the role of neck afferents on tactile orientation in seated and supine positions. The results showed that, in the supine position, the tactile E-effect was twice as large as in the seated position. These experiments confirm that tactile perception of orientation is affected by neck afferents, and show that the influence of neck afferents is limited by relevant gravitational cues.

Adult↗
PubMed1999

Visual contribution to self-induced body sway frequencies and visual perception of male professional dancers.

We studied the degree of dependence on vision, for postural control and for perception, among male adult dancers and untrained subjects. First, body sways were analyzed on a free seesaw platform. Fast Fourier transform processing allowed spectral frequency analysis of the platform sways recorded by an accelerometer. Secondly, a visual dependence test, the rod and frame test (RFT) was used. Professional dancers were significantly more stable and less dependent on vision for postural control and for perception than untrained subjects. Presumably, professional dance training strengthens the accuracy of proprioceptive inputs and shifts sensorimotor dominance from vision to proprioception. For the dancers, there was interaction between the RFT visual dependence and the visual control of posture: the less visual-dependent they were for the RFT, the more stable they were in dynamic balance conditions.

Adolescent↗
PubMed1999

The properties of chimeric picornavirus IRESes show that discrimination between internal translation initiation sites is influenced by the identity of the IRES and not just the context of the AUG codon.

The internal ribosome entry segment (IRES) of picornaviruses consists of approximately 450 nt of 5'-untranslated region, terminating at the 3' end with an approximately 25 nt element consisting of an absolutely conserved UUUC motif followed by a more variable pyrimidine-rich tract and G-poor spacer, and finally an AUG triplet, which is considered to be the actual ribosome entry site. Events following entry at this site differ among picornaviruses: in encephalomyocarditis virus (EMCV) virtually all ribosomes initiate translation at this site (AUG-11); in foot-and-mouth-disease virus (FMDV), one-third of the ribosomes initiate at this AUG (the Lab site), and the rest at the next AUG 84 nt downstream (Lb site); and in poliovirus (PV), the AUG at the 3' end of the IRES (at nt 586 in PV type 1) is considered to be a silent entry site, with all ribosomes initiating translation at the next AUG downstream (nt 743). To investigate what determines this different behavior, chimeras were constructed with a crossover at the conserved UUUC motif: the body of the IRES, the sequences upstream of this UUUC motif, was derived from one species, and the downstream sequences from another. When the body of the FMDV or PV IRESes was replaced by that of EMCV, there was a marked increase in the absolute and relative frequency of initiation at the upstream AUG, the Lab site of FMDV and 586AUG of PV, respectively. In contrast, when the body of the EMCV IRES was replaced by that of PV, initiation occurred with no preference at three AUGs: the normal site (AUG-11), AUG-10 situated 8 nt upstream, and AUG-12, which is 12 nt downstream. Thus although the context of the AUG at the 3' end of the IRES may influence initiation frequency at this site, as was shown by improving the context of 586AUG of PV, the behavior of the ribosome is also highly dependent on the nature of the upstream IRES. Delivery of the ribosome to this AUG in an initiation-competent manner is particularly efficient and accurate with the EMCV IRES.

5' Untranslated Regions↗
PubMed1998

Isotropic visual field effect on spatial orientation and egocentric localization.

The aim of this paper is to demonstrate the presence of a similar visual field effect on both spatial orientation and egocentric localization. A first experiment explored an orientation task (Visually Perceived Vertical or VPV determination) and compared the effects of a frame inclined either in the midfrontal plane (in this condition subjects assessed roll VPV) or in the median plane (subjects assessed pitch VPV) or in both combined planes (subjects assessed both roll and pitch VPV). A second experiment compared the frame effects specified above to the frame effect observed in an egocentric localization task (Visually Perceived Eye Level judgment) performed with a frame slanted in the median plane. The results showed that angular frame variations from -15 to +15 deg result in the same psychometric function for both orientation and localization tasks. In each experiment, correlations showed that individual differences occur in relation to an overall sensitivity to the visual field. Individual sensitivity may be accounted for by a ratio of visual to graviceptive information which remains constant whatever the perception plane (midfrontal or median plane) and whatever the task (spatial orientation or localization).

Adult↗
PubMed1998

Head orientation involvement in assessment of the subjective vertical during whole body tilt.

The aim of this research was to investigate the involvement of head tilt in the assessment of the subjective vertical during whole body tilt. For inclinations up to 28 degrees, it appears that the whole body tilt gives rise to more important deviations towards its direction (A-effect) than when the tilt was restricted to the head. A multiple regression analysis shows that errors in head-tilt condition partially account for the global errors observed in condition of whole body tilt. Other factors (relative to the degree of inclination) also played a role in the determination of the subjective vertical in whole body tilt but were less important than head tilt. These results are highly compatible with the assumption of head orientation as the major determinant in roll-tilt effects.

Adolescent↗
PubMed1998

The role of head-centric spatial reference with a static and kinetic visual disturbance.

A static or kinetic visual disturbance affects subjects' ability to estimate the direction of the gravitational vertical. This kind of error is increased by a head roll inclination. In two experiments, we combined head orientation with a static (Experiment 1: tilted frame) versus kinetic (Experiment 2: rotating disk) visual disturbance. The results showed that with a static visual disturbance, the increase of errors in the inclined head condition was mainly the consequence of a postural head effect like an Aubert effect. On the contrary, with a kinetic visual disturbance, it appears that the disk effect increases with head inclination. However, individual errors observed with the head inclined in front of a stationary disk were systematically correlated with the errors triggered by the same head inclination in front of a rotating disk. These observations confirm that the head axis spatial reference plays an important role in orientation perception, whatever the head position and the kind of visual display.

Adolescent↗
PubMed1997

The proteolytic cleavage of eukaryotic initiation factor (eIF) 4G is prevented by eIF4E binding protein (PHAS-I; 4E-BP1) in the reticulocyte lysate.

A common feature of viral infection is the subversion of the host cell machinery towards the preferential translation of viral products. In some instances, this is partly mediated by the expression of virally encoded proteases which lead to the cleavage of initiation factor eIF4G. The foot-and-mouth disease virus encodes two forms of a cysteine proteinase (L protease) which bisects the eIF4G polypeptide into an N-terminal fragment containing the eIF4E binding site, and a C-terminal fragment which contains binding sites for eIF4A and eIF3 and which associates with the 40S ribosomal subunit. Previously, we have demonstrated that the cleavage of eIF4G by L protease stimulates the translation of uncapped transcripts encoding cellular proteins and supports internal initiation driven by picornavirus internal ribosome entry segment (IRES) elements. Use of reticulocyte lysates manipulated to deplete them of eIF4E and the N-terminal fragment suggests that the C-terminal fragment of eIF4G is responsible for these effects, and we have now confirmed this by purifying the C-terminal fragment and analysing its effects directly in the absence of L protease. Interestingly, we find that pre-incubation of reticulocyte lysates or ribosomal salt wash fractions with the specific eIF4E binding protein, PHAS-I (eIF4E-BP1), blocks the proteolytic cleavage of eIF4G by L protease. This effect can be reversed by addition of recombinant eIF4E. These data are consistent with a model whereby the L protease cleavage site in eIF4G is inaccessible until a change in conformation is induced by the binding of eIF4E. This may have implications for a role for eIF4E binding in triggering changes that expose other domains in the eIF4G molecule during initiation of translation.

Animals↗
PubMed1997

Selection of spatial frame of reference and postural control variability.

The present paper addresses the question of the possible links between perceptive visual field dependence-independence and the visual contribution to postural control. In our differential approach, visual field dependent (FD) and independent (FI) subjects were selected on the basis of their score in the Rod and Frame Test (subjective vertical). The hypothesis that we have tested is that the FD subjects use mainly visual cues for estimating not only their subjective vertical but also their body orientation and stability. Moreover, we have postulated that these subjects use mainly dynamic visual cues to control their postural stability. In the postural test, the selected subjects were instructed to stand in the sharpened Romberg position in darkness and under normal or stroboscopic illumination, in front of either a vertical or a tilted frame. Lateral head and body orientation and stability were measured. We found that: (1) all subjects leaned slightly towards the tilted frame (postural frame effect), and this was obtained on the basis of the static visual cues alone; (2) FD subjects were less stable than FI subjects, and their stability required the use of dynamic visual cues, mainly extracted from the vertical frame. In FI subjects, static visual cues may act as a complementary regulation, enhancing stability even with a strobe tilted frame. We thus demonstrate that visual field dependence interacts with the visual contribution to postural control.

Adult↗
PubMed1997

Subjective vertical and postural activity.

Three experiments were conducted to test the effect of postural information, resulting from the active control of balance, on the perception of the vertical. Subjects were required to adjust a luminous rod in two different visual contexts: in the dark or within a tilted visual frame. In these experiments, postural activity was manipulated by placing observers either in a situation of slight postural imbalance (Experiment 1) or in a situation of postural immobilization (Experiment 2). In both situations performance was compared with a control condition in which subjects were standing upright freely (Experiment 1) or sitting unconstrained (Experiment 2). Results showed no main effect of active posture or of immobilization on the visual perception of the vertical. In the third experiment, subjects were supine with their Z body axis perpendicular to the plane of the luminous rod. Thus, body orientation relative to gravity was modified and motor activity reduced. In this position, the physical vertical was perceived quite accurately in a dark environment. Moreover, in the titled frame condition, the supine body position clearly improved vertical judgements. These results are discussed in relation to the ecological theory of orientation.

Humans↗
PubMed1997

Strobe frequency in the rod and frame effect.

This experiment dealt with the role of strobe frequency on the rod and frame effect in frame-dependent and frame-independent subjects in light of the destabilizing effect of strobe lighting on body posture. Analysis showed that the frame effect was resistant to strobe illumination and was significantly stronger at 2 Hz than at 9 Hz. Since the stroboscopic effect was not related to the extent of the frame effect observed in normal light, there was no over-all dependence on the different components of the visual field (static and kinetic). Moreover, analysis of eye movements during stroboscopic exposure confirmed previous observation of a visual scanning style related to orienting activity.

Adult↗
PubMed1996

A reevaluation of the cap-binding protein, eIF4E, as a rate-limiting factor for initiation of translation in reticulocyte lysate.

The cap-binding eukaryotic initiation factor, eIF4E, is a key target for the regulation of translation in mammalian cells and is widely thought to be present at very low molar concentrations. Here we present observations with the reticulocyte lysate that challenge this view. When reticulocyte ribosomes are harvested by centrifugation, most (approximately 75%) of the eIF4E remains in the postribosomal supernatant (PRS). In a reconstituted translation system we find that the ribosome-associated eIF4E alone can sustain much of the overall activity, suggesting that much of the factor in the PRS is functionally redundant. Consistent with this, our estimates of eIF4E in the reticulocyte lysate reveal much higher concentrations than previously reported. The association of a small proportion of eIF4E with the ribosome fraction appears to be functional and dependent on interaction with the factor eIF4G. This fraction of eIF4E is, as expected, more highly phosphorylated than that in the PRS; however, at least half the total phosphorylated eIF4E in reticulocyte lysate translation systems resides in the PRS fraction, suggesting that, while phosphorylation may enhance activity, it is not in itself sufficient to promote utilization of the factor. We also show that the eIF4E-binding factor, eIF4E-BP1 or PHAS-I, which regulates eIF4E activity in insulin-responsive cells, is present in the reticulocyte PRS at an approximately 1:1 molar ratio relative to eIF4E and demonstrate by co-immunoprecipitation studies that the binding of PHAS-I and eIF4G to eIF4E is mutually exclusive. These data are consistent with a potential regulatory role for PHAS-I in the reticulocyte lysate.

Amino Acid Sequence↗
PubMed1996

The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E.

The foot and mouth disease virus, a picornavirus, encodes two forms of a cysteine proteinase (leader or L protease) that bisects the EIF4G polypeptide of the initiation factor complex eIF4F into N-terminal (Nt) and C-terminal (Ct) domains. Previously we showed that, although in vitro cleavage of the translation initiation factor, eIF4G, with L protease decreases cap-dependent translation, the cleavage products themselves may directly promote cap-dependent protein synthesis. We now demonstrate that translation of uncapped mRNAs normally exhibits a strong requirement for eIF4F. However, this dependence is abolished when eIF4G is cleaved, with the Ct domain capable of supporting translation in the absence of the Nt domain. In contrast, the efficient translation of the second cistron of bicistronic mRNAs, directed by two distinct Internal Ribosome Entry Segments (IRES), exhibits no requirement for eIF4E but is dependent upon either intact eIF4G or the Ct domain. These results demonstrate that: (i) the apparent requirement for eIF4F for internal initiation on IRES-driven mRNAs can be fulfilled by the Ct proteolytic cleavage product; (ii) when eIF4G is cleaved, the Ct domain can also support cap-independent translation of cellular mRNAs not possessing an IRES element, in the absence of eIF4E; and (iii) when eIF4G is intact, translation of cellular mRNAs, whether capped or uncapped, is strictly dependent upon eIF4E. These data complement recent work in other laboratories defining the binding sites for other initiation factors on the eIF4G molecule.

Animals↗
PubMed1995

Proteolytic cleavage of initiation factor eIF-4 gamma in the reticulocyte lysate inhibits translation of capped mRNAs but enhances that of uncapped mRNAs.

Infection of cells with the foot-and-mouth-disease virus, a member of the picornavirus family, results in the shut-off of host protein synthesis. A major contributory mechanism is the proteolytic destruction of the gamma subunit of the complex eIF-4, which functions in translation to promote the binding of the 43S ribosomal preinitiation complex to the 5' end of the cellular mRNA molecules bearing a 5' terminal cap structure. Picornavirus RNA molecules, which are uncapped, use a distinct mechanism for translational initiation, which can operate in the absence, or at low levels, of eIF-4. The proteolysis of eIF-4 gamma in cells infected by foot-and-mouth-disease virus results from expression of a virus-encoded cysteine proteinase known as Leader (or L) protease. We have used a transcription plasmid encoding this protease as a tool to deplete in vitro translation systems of eIF-4 gamma in order to elucidate in more detail the role of this polypeptide in the control of translation. Using in vitro transcribed mRNAs we have observed a marked contrast between capped and uncapped transcripts in the response of their translation to the proteolysis of eIF-4 gamma. Translation of capped mRNAs is, as expected, severely impaired, and is restored by addition of eIF-4 complex containing the intact gamma-subunit. On the other hand, translation of uncapped transcripts, normally inefficient, is substantially enhanced. The data suggest that the translation of uncapped mRNAs may be stimulated in this system by one or more of the proteolytic degradation products of eIF-4 gamma.

3C Viral Proteases↗