We have shown previously that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed "natural" apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum- and 25 mM KCl-containing medium to serum-free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine-protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis.

We have shown previously that pigment epithelium-derived factor (PEDF) acts as a survival factor for cerebellar granule cell neurons in culture, as well as protecting them against glutamate toxicity. In this study we have examined effects of PEDF on apoptotic cell death. We find that the granule cells die of apoptosis throughout the culture period, what we have termed "natural" apoptosis. PEDF prevents this natural apoptosis if added to immature cells, within the first 2 days in vitro (DIV), and the effect is maintained for up to DIV12. However, PEDF has no effect if added to mature cells at DIV5. Similar results are obtained when apoptosis is induced by shifting the cells from a serum- and 25 mM KCl-containing medium to serum-free medium with 5 mM KCl. PEDF most effectively blocks induced apoptosis in immature cells (DIV2) when added 24 hr prior to the change of medium, but still provides some protection when added simultaneously. However, 24 hr pretreatment with PEDF has a minimal effect when apoptosis is induced in mature DIV6 cells; addition at the same time is completely ineffective. Two polypeptide fragments of PEDF, only one of which contains the serine-protease inhibitory site, are equally active, supporting previous results which suggest that the neurotrophic effects of PEDF are not mediated by protease inhibition. We conclude that PEDF protects immature but not mature granule cells against both natural and induced apoptosis.

A Japanese woman was treated with injectable methylprednisolone and oral prednisolone for dermatomyositis. On admission, her serum was positive for anti-hepatitis C virus (HCV) antibodies, although HCV RNA was undetectable on polymerase chain reaction. Glucocorticoid therapy improved the dermatomyositis; however, the serum alanine aminotransferase levels rapidly increased, with positive serum HCV RNA and a high viral titer. Both parameters decreased in association with prednisolone tapering, whereas dermatomyositis subsequently recurred and the administration of glucocorticoid therapy was repeated. The serum alanine aminotransferase and HCV RNA levels subsequently increased in a similar manner to that observed after the first course of therapy. Liver enzymes and the viral load should be monitored in anti-HCV-positive patients receiving immunosuppressives, even if serum HCV RNA is negative.

Summary:Purpose: To disclose possible epileptologic differences between photosensitive and nonphotosensitive patients with seizures induced by electronic screen games (ESGs).Methods: In patients with ESG-induced seizures who showed photo-and pattern sensitivity, magnetoencephalography (MEG) and EEG were performed simultaneously during ESG play, and equivalent current dipoles (ECDs) of the MEG spikes were estimated. In patients without ESG-induced seizures, who were surgical candidates, the intracranial EEG was analyzed for changes in epileptiform spike frequency.Results: Fifteen of 29 patients were photo-or pattern sensitive, and they had a posterior predominance of ECDs of the MEG spikes. In contrast, nonphotosensitive patients had an anterior predominance of ECDs. Other seizure-precipitating factors in the nonphotosensitive patients included hand manipulation or spatial processing. In patients without a history of ESG-induced seizures who underwent intracranial EEG monitoring for surgical evaluation, ESG playing induced changes in spike frequency in the supplementary motor area, perisylvian region, and medial temporal lobe.Conclusions: In photosensitive patients, interictal MEG spikes arise predominantly from the posterior region of the brain. In nonphotosensitive patients, epileptiform spikes tend to originate in the anterior part of the brain. Thus factors involving functions of the anterior part of the brain other than photo-or pattern sensitivity may play a role in the induction of seizures during ESG play. Furthermore, the changes in spike frequency in specific brain areas may correspond to their involvement in praxic activity and emotional changes during ESG play. A chance occurrence of seizures during ESG play also was observed. Key Words: Electronic screen game -induced seizures-Photosensitivity-Praxis sensitivity-Magnetoencephalography-Intracranial EEG.The most important factors contributing to the induction of seizures by video games or electronic screen games (ESGs) are photosensitivity and pattern sensitivity (1-3). The stimuli in the ESGs include flashing lights, rapid color changes, geometric patterns, and shifting scenes. In laboratory testing, some patients with ESGinduced seizures will show n o electroclinical evidence of pattern sensitivity or photosensitivity (2,4). In addition to general precipitating factors such as sleep deprivation and fatigue, nonphotosensitive factors such as proprioceptive stimuli from ocular muscles or eyelids, rapid and prolonged manual movements, emotional changes, psychic tension, and thought processing or decision making may have a role in the appearance of ESG-induced seizures in a minority of cases (5,6). The relevance of these factors has been poorly investigated, however. Harding (7) attributed the insensitivity to intermittent photic stimulation (IPS) or patterns to inadequate testing.Address correspondence and reprint requests to Dr. Y. Inoue at National Epilepsy Center, Shizuoka Higashi Hospital, Urushiyama 886, Shizuoka 420, Japan. E-mail: yushi@szec.hosp...