Biomedical subjects

J Pratt

Publications and source records attributed to J Pratt.

At least 37 records · Page 2Linked to original sources

PubMed2000

Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity.

Indeno¿1,2-bpyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (>10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na(+),K(+)-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.

Animals↗

PubMed2000

4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with in vivo activity.

A novel series of 2-substituted-4,5-dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazine derivatives was synthesised. One of them, 4e-a highly water soluble compound exhibited a nanomolar affinity and demonstrated competitive antagonist properties at the ionotropic AMPA receptors. This compound also displayed potent anticonvulsant properties against electrically or sound-induced convulsions in mice after systemic administration, thus suggesting adequate brain penetration.

Animals↗

PubMed2000

8-Methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazines: highly potent in vivo AMPA antagonists.

A novel series of readily water soluble 8-methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]++ +pyrazines were synthesized. The -10-yl acetic acid ((+)-3) and -10-carboxylidene (4) derivatives exhibit potent affinities (IC50=4 and 19 nM, respectively) and antagonist properties (IC50 = 2 and 3 nM, respectively) at the ionotropic AMPA receptor. These compounds also display anticonvulsant properties against both electrically and sound-induced convulsions in mice after ip, sc and iv administration with ED50 values between 0.9 and 11 mg/kg, thus suggesting adequate brain penetration.

Animals↗

PubMed2000

Sex crimes and the new punitiveness.

In the last few years, new ways of punishing sex offenders have been introduced in many modern societies. However, these sanctions have a broader significance than this: they are part of a broader set of penal arrangements-directed at the criminal population as a whole-which represents a new punitiveness. This seems to be moving the direction of legal punishment beyond the established parameters that had hitherto been set for it in modern society. This had involved punishment becoming increasingly administered by penal bureaucracies, to the exclusion of the general public, being influenced by the opinion of penal experts, and becoming more tempered, consistent and purposeful in form. Sanctions that did not fit these criteria faded out of modern penality. The indeterminate prison sentence was introduced at its outer limits as a residual measure of control to be used against those offenders-frequently sex criminals-for whom the existing penal framework was thought inappropriate. Even so, by the 1970s, these special penal measures were falling into disuse. However, the new punitiveness has not only given new life to them, but has also led to the introduction of measures which seem to reverse or move beyond modernpenal parameters. The article argues that the reasons for these shifts lie in the profound economic and social changes that have taken place in Western societies over the course of the last two decades or so.

Adult↗

PubMed2000

Estimating the components of the gap effect.

The gap effect refers to the finding that saccadic latencies are typically reduced when a fixation point is removed prior to the appearance of a peripheral target. This reduction in saccadic reaction time (SacRT) is thought to be due to a general warning effect and an oculomotor specific fixation offset that occur when the fixation point is removed. In order to estimate the contribution of each of these effects to the overall gap effect, this paper introduces a new manipulation, the partial-gap trial, where the fixation point undergoes a change in size prior to the presentation of the target. The partial-gap trial is presumed to provide the visual warning effect of the fixation offset (i.e. similar to that in a gap trial) but does not provide the fixation offset effect (FOE). When the fixation point was abruptly reduced in size before the presentation of the target, the estimated decrease in SacRT due to the visual warning effect was 5-7% and did not differ in the presence or absence of an auditory warning signal. It was found that auditory warning effect and the FOE interacted in reducing SacRTs. Additionally, when the fixation point was abruptly increased in size before the presentation of the target, SacRTs were slower than when the fixation point did not change in size and remained present for the entire trial (i.e. an overlap trial). We conclude that this new partial-gap paradigm is a useful method for researchers wishing to separately examine FOE and visual warning effects.

Adult↗

PubMed2000

Inhibition of return in saccadic eye movements.

Inhibition of return (IOR) is a phenomenon in which responses generated to targets at previously attended locations are delayed. It has been suggested that IOR affords a mechanism for optimizing the inspection of novel locations and that it is generated by oculomotor reflexes mediated by the superior colliculus. In this investigation, we measured the effects of IOR on the metrics of saccadic eye movements made to novel and previously attended locations. Saccades made to cued target locations, as well as to other targets within the same hemifield, had longer latencies than saccades made towards the novel, uncued hemifield. We further found that the amplitudes of saccades towards the cued hemifield were more hypometric, but only when the amplitude could not be pre-programmed. These results provide evidence that IOR influences spatial, as well as temporal, parameters of saccadic eye movements and suggest that the exogenous orienting of attention, in addition to influencing target detection, also influences oculomotor programming.

Adult↗

PubMed2000

Lipase activity from strains of Pasteurella multocida.

Thirteen clinical isolates of Pasteurella multocida from a variety of different animals and humans were examined for their ability to produce lipase. Lipase substrates used included Tween 20, Tween 40, Tween 80, and Tween 85. Lipase activity was detected in the filtrates of organisms grown to the exponential phase in Roswell Park Memorial Institute-1640 defined media (RPMI-1640), but activity increased in the filtrates when the cultures were allowed to proceed to the stationary phase. All strains examined (except for serotype 2) showed lipase activity against at least one of the Tweens. Tween 40 was the best substrate to demonstrate lipase activity. Pasteurella multocida serotype 8 produced the most active lipase against Tween 40 (3,561.7 units of activity/microgram of protein). This activity continued to increase after P. multocida entered a stationary growth phase. P. multocida lipase activity was optimal at pH 8.0. Lipase activity of P. multocida serotype 8 was eluted from a Sepharose 2B column at several points, indicating that several lipases may be produced in vitro by this organism. These data demonstrate that clinical isolates of P. multocida produce lipase; therefore, this enzyme should be considered a potential virulence factors for this organism.

Animals↗

PubMed2000

8-Methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e] pyrazine-4-ones: highly in vivo potent and selective AMPA receptor antagonists.

Water soluble 8-methylureido-10-amino-10-methyl-imidazo[1,2-a]indeno[1,2-e]pyraz ine-4-one 4 represents a novel class of highly potent and selective AMPA receptors antagonists with in vivo activity. The dextrorotatory isomer (+)-4 was found to display the highest affinity with an IC50 of 10 nM. It also exhibited very good anticonvulsant effects after i.p., s.c. and i.v. administration in mice subjected to electrical convulsions (MES) and i.p. in audiogenic seizure-e in DBA/2 mice (ED50's < or = 10 mg/kg).

Animals↗

PubMed2000

Oculocentric coding of inhibited eye movements to recently attended locations.

Results are reported for experiments that examined eye movements directed toward recently cued objects. In 1 experiment participants were slower to initiate saccades toward the earlier location of an object that had been cued, even though the cued object had subsequently moved away from that location. Other experiments involved exploring the reference frame within which the inhibited eye movements are encoded. These experiments revealed that the eye movement that is inhibited is encoded in an oculocentric-rather than an environmental-reference frame. However, simple detection as indexed by manual keypress responses is encoded in an environmental reference frame. The results have implications for inhibition of return, for the link between eye movements and attention, and for the nature of the spatial reference frames in which both covert and overt movements of attention are encoded.

Adult↗

PubMed2000

The role of the fixation location in inhibition of return.

Experiments that have examined inhibition of return (IOR) have typically used trial sequences in which attention is reoriented to a central fixation location between the presentation of the peripheral cue(s) and the target. In examining the role of the fixation location in IOR, three experiments were conducted in which an exogenous cue was used to reorient attention following a peripheral cue and before the appearance of a target. However, this cue occurred at either the traditional central fixation location or a nonfixated location. The results indicate that reorienting attention to a fixated location results in a significant reduction in the inhibitory effect. The results from the study suggest that IOR could serve as a mechanism that improves the efficiency of visual searches.

Attention↗

PubMed2000

Smooth muscle tumor of the pleura. A case report and review of the literature.

Smooth muscle tumors of the serosal membranes are extremely rare and have received little attention in the literature. To the best of our knowledge, only 1 published series of 5 pleural smooth muscle neoplasms has been published to date. We describe a primary pleural neoplasm with smooth muscle differentiation documented by light microscopy, immunohistochemistry, and electron microscopy. This tumor originated in the parietal pleura in a 32-year-old white man and was diagnosed incidentally by chest radiography; the diagnosis was confirmed by magnetic resonance imaging and biopsy. Four years later, the tumor was noted to have increased in size and disseminated into the chest wall as a separate circumscribed mass located in the pectoral muscle. Both masses were resected and diagnosed as smooth muscle tumors. We conclude that smooth muscle tumor of the pleura is a well-defined entity with a low, but definite malignant potential; therefore, we recommend complete resection and long-term follow-up for all patients.

Actins↗

PubMed1999

Spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives are mixed AMPA and NMDA glycine-site antagonists active in vivo.

Original spiro-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives were synthesised and led to the identification of 3e which showed good affinities for both the AMPA and the NMDA glycine-site receptors, and displayed good anticonvulsant effects after i.p. and i.v. administrations in the electroshock-induced convulsion assay in mice. The corresponding dextrorotatory isomer (+)-3e was notably more potent than the levorotatory isomer (-)-3e in in vitro and in vivo assays.

Animals↗

PubMed1999

The effect of riluzole and mannitol on cerebral oedema after cryogenic injury in the mouse.

A cryogenic lesion was produced under halothane anaesthesia in the mouse by placing a cotton swab soaked in liquid nitrogen onto the surface of the cranium. This provoked an oedematous lesion which developed within the hour after the insult and evolved over the following week. Treatment with mannitol at 3 g/kg i.v. caused a significant 22% reduction in oedema 1 h later, when administered immediately after lesion, but not when administered 23-h post lesion. Likewise riluzole (16 mg/kg, i.v.) significantly reduced oedema by 17% when administered immediately after lesion, or 13% (P < 0.05) when administered 23 h after lesion. Repeated doses (2 x 16 mg/kg, i.p.) of riluzole were also able to reduce oedema significantly (24%, P < 0.05) at 24 h post lesion. Riluzole, in four repeated doses of 8 mg/kg i.p. was also able to reduce lesion surface size by 16% (P < 0.05) 48 h after lesion.

Animals↗

PubMed1999

Autonomic cardiovascular control in children with obstructive sleep apnea.

Autonomic cardiorespiratory control changes with sleep-wake states and is influenced by sleep-related breathing disorders. Power spectrum (PS) analysis of instantaneous fluctuations in heart rate (HR) is used to investigate the role of the autonomic nervous system (ANS) in cardiorespiratory control. The two spectral regions of interest are the low frequency component (LF) and high frequency component (HF). The aim of the present study was to investigate the autonomic cardiorespiratory control in children with obstructive sleep apnea (OSA) syndrome. We studied 10 children with OSA versus 10 normal children. All subjects underwent whole night polysomnography. Spectral analysis of the HR and breathing signals was performed for 256 second long, artifact-free epochs in each sleep-wake state. The LF power was higher in the OSA group compared with control subjects for all states, reflecting enhanced sympathetic activity in OSA subjects. The results indicated sympathetic predominance during REM sleep in all subjects and parasympathetic predominance in slow wave sleep only in controls. The autonomic balance (LF/HF) was significantly higher in OSA patients than in control subjects, at all stages during night sleep, and while awake before sleep onset. An index of overall autonomic balance (ABI) was computed for each subject and correlated well with the measured respiratory disturbance index (RDI).

Autonomic Nervous System↗

PubMed1999

The Gap effect for spatially oriented responses.

The gap effect refers to the finding that a temporal gap between fixation point offset and target onset typically results in shorter saccadic latencies than if the fixation point remains on. Recently, this gap effect was found for aimed hand movements as well as saccadic eye movements, but not for simple keypress responses. In order to examine the hypothesis that the hand gap effect occurs for different types of spatially oriented movements, two experiments were conducted. In the first experiment, subjects produced spatially oriented responses to a peripheral target and the target location was known in advance of the targets presentation. This spatially oriented detection task yielded gap effects for both eye and hand responses. In the second experiment, the duration of the temporal gap was varied between 0-400 ms. The duration of the temporal gap had similar effects on the magnitudes of both the eye and hand gap effects, suggesting that a common mechanism may underlie the gap effect for saccadic and manual pointing movements. Overall, the results of the present experiments confirm the finding of a gap effect for spatially oriented hand movements and suggest that this effect may be related to the functioning of the superior colliculus.

Fixation, Ocular↗

PubMed1999

Inhibition of return in discrimination tasks.

Although inhibition of return is known to affect a wide range of detection tasks, it has not been found consistently in discrimination tasks. To examine this issue, 5 experiments were conducted in which participants discriminated between a visual target and a distractor. The responses were not inhibited if, before the onset of stimuli, attention had been overtly oriented (i.e., an eye movement was made) to the future target location and the stimulus at that location was the same symbol as the upcoming target. However, if attention was covertly oriented (i.e., no eye movement was made) to the future location of the target, or if the stimulus at the earlier attended location was a symbol different from the target, responses to the target were inhibited. Overall, the findings provide insights into the relation between movements of attention and discrimination judgments and support the notion that inhibition of return is an attentional phenomenon.

Adult↗

PubMed1999

Age differences in saccadic averaging.

Younger and older adults were asked to saccade to an orientation-defined target that was presented alone, with a more central distractor, or with a more peripheral distractor. Both age groups exhibited saccadic averaging that was more pronounced in the central distractor condition, wherein older adults had the larger effect. These results are relevant to questions of oculomotor control and also have implications for the study of age differences in other visually guided behaviors.

Adult↗

PubMed1999

Experience of discordant beta hCG results by different assays in the management of non-seminomatous germ cell tumours of the testis.

Fifty-five patients with non-seminomatous germ cell tumours (NSGCT) who were referred to a regional clinical oncology centre over a 3-year period were assessed prospectively with assays of the serum tumour markers alpha-feto protein (AFP) and beta-human chorionic gonadotropin (beta hCG). Paired baseline beta hCG assays were undertaken using a polyclonal radioimmunoassay (RIA) and a monoclonal fluoroimmunoassay (FIA). Serial paired measurements were undertaken in patients showing discordance on baseline assays. Four patients (7%; 95% confidence interval 0-14) showed discordance between the paired beta hCG assays. Of these, two showed elevated beta hCG on RIA, with normal levels on FIA; two showed elevated beta hCG on FIA, with normal levels on RIA. No discordance was noted with AFP assays. Discordance persisted in two of the patients (50%) and disappeared on treatment in one (25%); one patient died during treatment. Discordant beta hCG assays present difficulties in interpretation and have therapeutic implications in patients with NSGCT. No single currently available assay is conclusive in all patients and commercial assay kits should be chosen with care.

Adult↗