A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program.

The molecular mechanism(s) that are responsible for suppressing MyoD's transcriptional activities in undifferentiated skeletal muscle cells have not yet been determined. We now show that MyoD associates with a histone deacetylase-1 (HDAC1) in these cells and that this interaction is responsible for silencing MyoD-dependent transcription of endogenous p21 as well as muscle-specific genes. Specifically, we present evidence that HDAC1 can bind directly to MyoD and use an acetylated MyoD as a substrate in vitro, whereas a mutant version of HDAC1 (H141A) can not. Further more, this mutant also fails to repress MyoD-mediated transcription in vivo, and unlike wild-type HDAC1 it can not inhibit myogenic conversion, as judged by confocal microscopy. Finally, we show that an endogenous MyoD can be acetylated upon its conversion to a hypophosphorylated state and only when the cells have been induced to differentiate. These results provide for a model which postulates that MyoD may be co-dependent on HDAC1 and P/CAF for temporally controlling its transcriptional activity before and after the differentiation of muscle cells.

Idiopathic epilepsy and school achievement.

Forty one children (20 boys, 21 girls) aged 6-10.8 years (mean age 8.6 years) who were affected with idiopathic epilepsy underwent neuropsychological (Wechsler Intelligence Scale for Children, Bender test) and behavioural assessment (Personality Inventory for Children; this was also used in a matched control group). Further information was obtained by teachers' reports. School underachievement occurred in 25 children (61%). Statistical analysis showed no influence of sex, social background, age of onset, seizure type, duration of illness, features seen on electroencephalography, and treatment. School failure was due to poor performance in almost all academic fields, and was associated with higher visuomotor impairment; children showing good school performance had a higher mean IQ and less visuomotor impairment. The behaviour of children with epilepsy who had a good academic performance did not differ from that of their healthy peers. Emotional maladjustment (social skill impairment, depression, poor motivation, and low self esteem) was associated with poor school performance. Such problems, that may complicate the course of idiopathic epilepsy and require an appropriate educational programme, should be carefully considered by the clinician.

Computerized electroencephalographic assessment of congenital brain infarction.

We studied 12 children (8 female and 4 male) aged 2.2-14.3 years, whose computed tomographic (CT) examination had shown evidence of malacic and/or porencephalic outcomes of early vascular brain infarction. Topographic spectral electroencephalographic (EEG) analysis was performed in all patients in the awake state. The following spectral EEG variables were studied: topography, absolute and relative power of delta, theta, alpha, beta bands, overall power, and peak alpha frequency asymmetries. The results of topographic spectral EEG analysis were compared with the localization and nature of lesions as detected by CT scans. Depending on the nature of the lesions, we were able to identify two different spectral patterns. Porencephalic cysts were characterized by an increase in delta and theta bands in the areas surrounding the lesion sites, as identified by CT. Spectral EEG patterns of malacic outcomes resulted in a focal increase in theta and delta band power, corresponding to the topography of lesions. Moreover, in 9/12 subjects an asymmetry of alpha rhythm in occipital leads was found homolaterally to the lesion sites, associated with a decrease in power, without any CT evidence of an occipital lesion.

[Continuous localized EEG discharge during sleep in children without neuropsychological problems]. / Décharges EEG localisées continues pendant le sommeil chez des enfants sans troubles neuropsychiques.

After having reported continuous localized EEG discharge during slow sleep (CLEDS) in six children with congenital encephalopathy, we observed a similar EEG picture in six children free from both neuropsychological and neuroradiological defects. They suffered from partial idiopathic epilepsy; five presented a familial disposition towards febrile seizures. Continuous paroxysmal activity during sleep was observed from 4.8 yrs to 4.11 yrs (mean age: 4.9 yrs). Spontaneous remission of CLEDS was observed in three cases after 2-25 months, but one or more relapses occurred in two cases, and five children are still suffering from CLEDS. Seizures were controlled by drugs in all cases. Deterioration of intelligence level, although not severe, was observed in one case, after 24 months of CLEDS.

Partial childhood epilepsy and reaction time: the effect of interictal EEG discharges.

A study was conducted on seven children (five females and two males, aged 5.7-13.1 years) affected with partial epilepsy which was well controlled by therapy. A computer was connected on-line to a polygraph and during two EEG recordings, the subject had to react to the appearance of a colored rectangle on the display screen by pushing a key on the keyboard: these events were automatically marked on the trace of a polygraphic channel. By means of Anova analysis it was demonstrated that during the same recording, reactions simultaneous to paroxysmal discharges were not significantly slower than those measured during free intervals. However, in the same patient, reaction times were significantly prolonged during recordings characterized by a higher rate of EEG paroxysmal activity.

Severe outcome of brain perfusion failure: a pre-hydranencephalic state?

Four children surviving severe hypoxic-ischemic brain damage showed subtotal destruction of the cerebral hemispheres, with partial preservation of some infratentorial and supratentorial brain structures. True multicystic encephalopathy features were identified in two cases on CT scanning. The other patients showed more pronounced brain tissue destruction, with overall malacia of the hemispheres. An echographic study demonstrated that the brain damage occurred progressively, within about one month, and was preceded by oedema, white matter malacia and cavitation. The role of the compensatory mechanisms responsible for preservation of structures supplied by the vertebral-basilar circle is discussed. The authors suggest that the observed outcome could be considered a stage immediately preceding the most severe damage represented by hydranencephaly.