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S Clare

Publications and source records attributed to S Clare.

28 records · Page 2Linked to original sources
PubMed1999

Functional magnetic resonance imaging: clinical applications and potential.

Demonstration that contrast in magnetic resonance images can be generated based on differences in blood oxygenation has led to an explosion of interest in so-called functional magnetic resonance imaging (FMRI). FMRI can be used to map increases in blood flow that accompany local synaptic activity in the brain. The technique has proved remarkably sensitive and has been used to map a broad range of cognitive, motor and sensory processes in the brain entirely non-invasively. More recently, efforts have been made to extend this technique to the analysis of clinical problems. A major application is for presurgical localization of cerebral functions, e.g. in the surgical treatment of epilepsy. The technique also is beginning to provide information on functional consequences of abnormal brain development. Perhaps most exciting are applications to neurological impairments that are not associated with structural abnormalities, such as learning problems, dyslexia and movement disorders. It is possible that useful applications of FMRI may be found for directly mapping sites of action of CNS-active drugs. Although the extent of the potential clinical applications of this new brain mapping technique is not clear, the widespread availability of MRI scanners suggests that the technique should in some form soon become a routine tool in major neuroradiological centres.

Humans↗
PubMed1999

Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium.

Spleen and peritoneal macrophages obtained from innately resistant A/J mice released low levels of interleukin 18 (IL-18) upon infection with Salmonella typhimurium C5 RP4. Incubating the cells with recombinant gamma interferon (rIFN-gamma) enhanced IL-18 production. A/J mice treated in vivo with anti-IL-18 antibodies showed impaired resistance to infection, with increased bacterial loads in the liver and spleen. Administration of rIL-18 could protect A/J mice from challenge with a lethal dose of virulent salmonellae, with a dramatic reduction in bacterial numbers in the tissues. rIL-18 administration did not ameliorate the disease in IFN-gamma-R-/- mice. IL-18 proved to be required for IFN-gamma production by mouse splenocytes from conventional, scid, and rag-1(-/-) mice; in vivo IL-18 neutralization caused a decrease in circulating IFN-gamma levels. Thus, IL-18 is a key factor in early host resistance to Salmonella and probably acts via IFN-gamma.

Animals↗
PubMed1998

Interleukin-12 is required for control of the growth of attenuated aromatic-compound-dependent salmonellae in BALB/c mice: role of gamma interferon and macrophage activation.

The attenuated S. typhimurium SL3261 (aroA) strain causes mild infections in BALB/c mice. We were able to exacerbate the disease by administering anti-interleukin-12 (IL-12) antibodies, resulting in bacterial counts in the spleens and livers of anti-IL-12-treated mice that were 10- to 100-fold higher than the ones normally observed in premortem mice; yet the animals showed only mild signs of illness. Nevertheless, they eventually died of a slow, progressive disease. Mice infected with salmonellae become hypersusceptible to endotoxin. We found that IL-12 neutralization prevented the death of infected mice following subcutaneous injection of lipopolysaccharide. Granulomatous lesions developed in the spleens and livers of control animals, as opposed to a widespread infiltration of mononuclear cells seen in the organs of anti-IL-12-treated mice. In the latter (heavily infected), salmonellae were seen within mononuclear cells, indicating an impairment of the bactericidal or bacteriostatic ability of the phagocytes in the absence of biologically active IL-12. Gamma interferon (IFN-gamma) levels were reduced in the sera and tissue homogenates from anti-IL-12-treated mice compared to those in control animals. Furthermore, fluorescence-activated cell sorter analysis on spleen cells showed that IL-12 neutralization impaired the upregulation of I-Ad/I-Ed antigens on macrophages from infected mice. Inducible nitric oxide synthase and IFN-gamma mRNA production was down-regulated in anti-IL-12-treated mice, which also showed an increased production of IL-10 mRNA and a decrease in nitric oxide synthase activity in the tissues. Administration of recombinant IFN-gamma to anti-IL-12-treated mice was able to restore host resistance, granuloma formation, and expression of major histocompatibility complex class II antigens in F4/80(+) and CD11b+ spleen cells.

Animals↗
PubMed1997

Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area.

Conventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo-planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple "go/no-go" motor paradigm. Comparison of activation patterns during "go" and "no-go" responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution.

Adult↗
PubMed1988

Prenatal morphine exposure and sleep-wake disturbances in the fetus.

We have previously shown that acute exposure to low-dose morphine stimulates arousal and breathing movements in the fetal lamb. We now report on the effects of subacute low-dose morphine exposure on the regulation of fetal sleep-wake behavior and breathing patterns. Morphine was infused to 11 fetal lambs (121-129 days gestation) at a constant rate of 400 micrograms/h for 7 days via a mini osmotic pump implanted subcutaneously in the maternal flank and connected directly to an indwelling catheter in the fetal vena cava. On day 1, morphine resulted in a state of arousal in all fetuses, with loss of quiet sleep and rapid eye movement (REM) sleep. This response was greatly reduced by day 2 and was insignificant by day 3, despite continuous drug exposure. There was no decrease in plasma morphine levels. Two fetuses died during morphine exposure. Upon removal of the pump, all fetuses exhibited disturbances in their sleep cycles within 1-3 h, with an increase in arousal time and loss of REM sleep. The duration of the arousal and quiet sleep episodes was also greatly reduced. Such disturbances were noted for 3-4 days after termination of morphine infusion. Four fetuses were delivered prematurely (131-136 days) during this period. These results demonstrate the rapid onset of tolerance to low-dose morphine exposure in the fetus and the development of physical dependence, as manifested by a mild abstinence syndrome characterized by sleep-wake disturbances.

Animals↗
PubMed1988

Dual action of morphine on fetal breathing movements.

Morphine has been reported to both stimulate and suppress fetal breathing movements (FBM). In light of these conflicting reports, we have conducted a systematic dose-response analysis of the effects of morphine on FBM in 27 fetal lambs. Morphine was infused directly to the fetus in doses ranging from 0.075 to 80 mg/hr. Low doses (0.075-2.5 mg/hr) resulted in a progressive increase in the relative incidence of FBM, whereas higher doses (greater than 2.5 mg/hr) decreased FBM with total apnea observed at 80 mg/hr. This biphasic response can be fitted as the sum of two sigmoidal log dose-response curves. Both stimulation and suppression of FBM by morphine were abolished by naloxone pretreatment, indicating that both responses are mediated by activation of opioid receptors. The dual action of morphine on FBM may be due to different opioid receptor subtypes or different sites of action.

Animals↗
PubMedDate not supplied

Drawing and the cerebral hemispheres: bilateral EEG alpha.

Bilateral EEG alpha (alpha) was measured during several cognitive tasks in two experiments. EEG alpha was suppressed relative to baseline in both hemispheres during every drawing and writing task. In addition, there were task-related EEG alpha asymmetries. Differences in left-hemisphere, but not right-hemisphere EEG alpha activity, were responsible for EEG alpha asymmetry differences between writing and drawing tasks. There was no difference in bilateral EEG alpha during drawing an upright versus an inverted drawing stimulus; failing to support Edward's (1977, 1979) 'cognitive shift' approach to drawing instruction.

Adolescent↗