Polygraphic recordings in subacute sclerosing panencephalitis. A study of the pathophysiology of the periodic EEG complexes

Polygraphic whole night recordings were performed in 10 patients with SSPE. In most cases sleep states could not be classified according to the usual criteria, but two different states with differing EEG patterns were always seen. A significant correlation was obtained between EEG complexes and phase of the respiratory cycle in 8 out of 9 patients, irrespective of the sleep state. Slowing of heart rate for one R-R interval was observed to occur during the onset of the complex in 7 patients in both sleep states, and in 2 patients only in one state. Periodic occurrence of complexes was stable throughout the night. This stability seems to be maintained by a mechanism regulating the duration of an interval according to the duration of the preceding one. It is suggested that diffuse involvement of subcortical structures rather than a localized change is responsible for the generation of the EEG complexes in SSPE.     

EEG alpha dynamics as viewed from EEG dimension dynamics

EEG alpha power covaries with changes in visual input and with changes in other aspects of cortical processing. We present an synopsis of three experiments that demonstrate these effects. A concurrent analysis of the EEG dimension indicates that the dynamics of EEG alpha may result from at least two different mechanisms.     

EEG evidence of stimulus-directed response dynamics in human somatosensory cortex

Dense multichannel recordings of scalp electroencephalogram (EEG) were obtained in the vicinity of primary somatosensory cortex, time-locked to repetitive vibrotactile stimulation of sites on the right index finger of a single human subject. Frequency-domain analysis of cross-trial averages revealed prominent 'driving' responses in the EEG at the frequency of stimulation, which under specific stimulus conditions displayed pronounced changes in amplitude and topographic organization over brief (4 s) durations of stimulus exposure. The changes were systematic and physiologically coherent, evolving toward driving-response topographies observed in the same subject in conjunction with periodic microstimulation of single mechanoreceptive afferents whose receptive fields occupied corresponding positions on the digit. This dynamic process was orderly and reproducible, and could be controlled by manipulating factors such as the amplitude, frequency, and temporal spacing of the stimuli. The results are tentatively interpreted in light of a previously proposed neurophysiological model of stimulus-driven response plasticity in mammalian somatosensory cortex.     

The dynamics of neurogenic signalling underlying bristle development in Drosophila melanogaster

We have examined expression of the neurogenic gene, Delta (Dl), and the regulatory relationships between the Delta-Notch signalling pathway and the proneural gene, achaete, during microchaeta development in Drosophila. Delta is expressed in all microchaeta proneural cells and microchaeta sensory organ precursors (SOPs) and is expressed dynamically in SOP progeny. We find that Delta expression in microchaeta proneural cells is detected prior to the onset of achaete expression and arises normally in the absence of achaete/scute function, indicating that initial Delta expression in the notum is not dependent on proneural gene function. Activation of the Delta-Notch pathway results in loss of Delta protein accumulation, suggesting that Delta expression is regulated, in part, by Delta-Notch signalling activity. We find that Delta signalling is required for correct delineation of early proneural gene expression in developing nota. Within microchaeta proneural stripes, we demonstrate that Delta-Notch signalling prohibits adoption of the SOP fate by repressing expression of proneural genes.     

Investigation of the mechanism underlying the inhibitory effect of heterologous ras genes in plant cells

The ras genes from yeast and mammalian cells were fused to plant expression promoters, and introduced into plant cells via Agrobacterium, to study their effect on cell growth and development. All introduced ras genes had a strong inhibitory effect on callus and shoot regeneration from plant tissues. This is consistent with earlier findings that heterologous ras genes were highly lethal to protoplasts following direct DNA uptake. These effects could not be reversed by increasing exogenous or endogenous cytokinin levels. These effects were also independent of the v-Ha-ras mutations in functionally important regions of Ras proteins such as effector-binding and membrane-binding sites. Similarly, co-transformation with the genes encoding the Ras-negative regulators, GTPase-activating protein and neurofibromin did not affect the ras inhibitory effect, indicating that the mechanism of ras inhibition of plant cells is not related to normal ras cellular functions. This conclusion was supported by further studies in which ras gene expression was modified using various promoters and antisense constructs. The introduced ras sequences remained fully inhibitory regardless of which promoters (inducible or tissue-specific) or which orientations (sense or antisense) were tested. This strongly suggests that the ras DNA sequence itself, rather than the Ras protein or ras mRNA, is directly involved in the inhibitory effect. The mechanism underlying this novel phenomenon remains unknown. Introduced ras genes may inhibit plant cell growth by inducing co-suppression of unknown endogenous ras or ras-related genes, thereby leading to the arrest of cell growth.     

The long-term course of spike and wave complexes in the waking EEG of chronic schizophrenics

Nineteen chronic schizophrenics (8 males and 11 females) showed at least one spike and wave complex (SpW) in their rested-awake EEGs during long-term neuroleptic treatment. The age at the first appearance of the SpW ranged from 16 to 60 years, and the duration of neuroleptic medication preceding its appearance was from 1 to 35 years. Two types of SpW waveform were discriminated; one was a diffuse high voltage isolated 3.5-4 Hz SpW complex, and the other a diffuse moderate voltage 5-6 Hz SpW burst. In EEG studies repeated over the long-term, the presence of SpW was transient in 11 cases, intermittent in 5 cases, and continuous in 3 cases. Three patients had generalized tonic-clonic clinical seizures; two of their EEGs did not show SpW until after the onset of seizures. All three responded well to adjunctive anticonvulsant therapy. The other 16 patients exhibited SpW but did not have clinical seizures with or without prophylactic use of anticonvulsants. The SpW in the EEG of chronic schizophrenics might be an indicator of predisposition for seizure, but it is not a good predictor of seizure.     

Nonlinear dynamics of epileptic seizures on basis of intracranial EEG recordings

PURPOSE: An understanding of the principles governing the behavior of complex neuronal networks, in particular their capability of generating epileptic seizures implies the characterization of the conditions under which a transition from the interictal to the ictal state takes place. Signal analysis methods derived from the theory of nonlinear dynamics provide new tools to characterize the behavior of such networks, and are particularly relevant for the analysis of epileptiform activity. METHODS: We calculated the correlation dimension, tested for irreversibility, and made recurrence plots of EEG signals recorded intracranially both during interictal and ictal states in temporal lobe epilepsy patients who were surgical candidates. RESULTS: Epileptic seizure activity often, but not always, emerges as a low-dimensional oscillation. In general, the seizure behaves as a nonstationary phenomenon during which both phases of low and high complexity may occur. Nevertheless a low dimension may be found mainly in the zone of ictal onset and nearby structures. Both the zone of ictal onset and the pattern of propagation of seizure activity in the brain could be identified using this type of analysis. Furthermore, the results obtained were in close agreement with visual inspection of the EEG records. CONCLUSIONS: Application of these mathematical tools provides novel insights into the spatio-temporal dynamics of "epileptic brain states". In this way it may be of practical use in the localization of an epileptogenic region in the brain, and thus be of assistance in the presurgical evaluation of patients with localization-related epilepsy.     

Investigation of the molecular mechanisms underlying growth factor synergy: the role of ERK 2 activation in synergy

Stem Cell Factor (SCF), the ligand for the c-kit proto-oncogene, has been shown to synergistically interact with other cytokines, enhancing the responsiveness of haemopoietic precursors. In this study we have examined the effects of SCF, in combination with interleukin-3 (IL-3), on FDCP-Mix A4 cells, a murine, multipotent, haemopoietic progenitor cell line. Low concentration of IL-3 act to enhance cell survival but do not stimulate proliferation in A4 cells. Similarly, SCF when added alone, acts as a good survival stimulus, but is a poor proliferative stimulus. However, in combination with low concentrations of IL-3, SCF stimulates a synergistic enhancement of proliferation leading to a large increase in cell number after seven days. The synergy observed was not due to SCF stimulated alterations in the mRNA, protein levels or affinity of the IL-3 receptors. Therefore, interactions between cytokines at the level of cytoplasmic signalling pathways were investigated. IL-3 stimulated the rapid and transient tyrosine phosphorylation of several proteins (including those of molecular weights 130, 110, 100, 95, 80, 65, 50 and 45 kDa). Some of these proteins were identified as the Src Homology Collagen (SHC) protein, Janus kinase (JAK-2) and the Mitogen Activated Protein Kinase isoforms ERK 1 and ERK 2. IL-3 also stimulated a transient increase in the activity of both ERK 1 and 2. SCF stimulated a rapid and transient increase in the tyrosine phosphorylation of ERK 1 and ERK 2 although, coaddition of SCF with IL-3, caused no gross differences in the phosphorylation of SHC, JAK-2 or ERKs compared to those observed with IL-3 alone. Coaddition of SCF and low concentration of IL-3 stimulated a reproducible synergistic increase in the activity of ERK 2, whereas only an additive increase in the activity of ERK 1 was observed. These results suggest that ERK 2 activation represents a point at which the two pathways, stimulated by IL-3 and SCF, interact synergistically.     

Identification of two distinct human SMC protein complexes involved in mitotic chromosome dynamics

The structural maintenance of chromosomes (SMC) family member proteins previously were shown to play a critical role in mitotic chromosome condensation and segregation in yeast and Xenopus. Other family members were demonstrated to be required for DNA repair in yeast and mammals. Although several different SMC proteins were identified in different organisms, little is known about the SMC proteins in humans. Here, we report the identification of four human SMC proteins that form two distinct heterodimeric complexes in the cell, the human chromosome-associated protein (hCAP)-C and hCAP-E protein complex (hCAP-C/hCAP-E), and the human SMC1 (hSMC1) and hSMC3 protein complex (hSMC1/hSMC3). The hCAP-C/hCAP-E complex is the human ortholog of the Xenopus chromosome-associated protein (XCAP)-C/XCAP-E complex required for mitotic chromosome condensation. We found that a second complex, hSMC1/hSMC3, is required for metaphase progression in mitotic cells. Punctate vs. diffuse distribution patterns of the hCAP-C/hCAP-E and hSMC1/hSMC3 complexes in the interphase nucleus indicate independent behaviors of the two complexes during the cell cycle. These results suggest that two distinct classes of SMC protein complexes are involved in different aspects of mitotic chromosome organization in human cells.